Mallotus philippinensis Muell. Arg (Euphorbiaceae ...

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Review Article Mallotus philippinensis Muell. Arg (Euphorbiaceae): Ethnopharmacology and Phytochemistry Review Mayank Gangwar, 1,2 R. K. Goel, 2 and Gopal Nath 1 1 Laboratory of Gastrointestinal Infections and Molecular Diagnosis, Department of Microbiology, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, India 2 Department of Pharmacology, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, India Correspondence should be addressed to Gopal Nath; [email protected] Received 15 February 2014; Revised 2 May 2014; Accepted 2 May 2014; Published 8 July 2014 Academic Editor: Kota V. Ramana Copyright © 2014 Mayank Gangwar et al. is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Mallotus philippinensis Muell. Arg (Euphorbiaceae) are widely distributed perennial shrub or small tree in tropical and subtropical region in outer Himalayas regions with an altitude below 1,000m and are reported to have wide range of pharmacological activities. Mallotus philippinensis species are known to contain different natural compounds, mainly phenols, diterpenoids, steroids, flavonoids, cardenolides, triterpenoids, coumarins, isocoumarins, and many more especially phenols; that is, bergenin, mallotophilippinens, rottlerin, and isorottlerin have been isolated, identified, and reported interesting biological activities such as antimicrobial, antioxidant, antiviral, cytotoxicity, antioxidant, anti-inflammatory, immunoregulatory activity protein inhibition against cancer cell. We have selected all the pharmacological aspects and toxicological and all its biological related studies. e present review reveals that Mallotus philippinensis is a valuable source of medicinally important natural molecules and provides convincing support for its future use in modern medicine. However, the existing knowledge is very limited about Mallotus philippinensis and its different parts like steam, leaf, and fruit. Further, more detailed safety data pertaining to the acute and subacute toxicity and cardio- and immunotoxicity also needs to be generated for crude extracts or its pure isolated compounds. is review underlines the interest to continue the study of this genus of the Euphorbiaceae. 1. Introduction Mallotus (family: Euphorbiaceae) is a large genus of trees and shrubs distributed chiefly in the tropical and subtropical regions of the Old World with around 20 species in India [1]. Mallotus philippinensis Muell. (commonly called Kamala, Kampillaka, and Kapila, and locally known as Shendri) is a very common perennial shrub or small tree found in outer Himalayas ascending to 1500 meters. Mature fruits have glandular hairs collected as reddish brown powder which is collected in cloth by shaking and rubbing the fruits by hand. e collected material is fine, granular powder, dull red, or madder red-colored and floats on water. is plant is traditionally used for antifilarial [2], antibacterial, anti-inflammatory, and immune-regulatory activity [3] and also used as purgative, anthelmintic, vulnerary, detergent, maturant, carminative, alexiteric and is useful in treatment of bronchitis, abdominal diseases, spleen enlargement, antimi- crobial, antiparasitic, and so forth (Figure 18). Some other medicinal plants reported similar anticesto- dal activity shown in Table 1. Some medicinal plants exported from India are Aconitum species (root), Acorus calamus (rhizome), Adhatoda vasica (whole plant), Berberis aristata (root), Cassia angustifolia (leaf and pod), Colchicum luteum (rhizome and seed), Hedychium spicatum (rhizome), and Heradeum candicans (rhizome) [4]. 1.1. Scientific Classification. Consider the following: kingdom: Plantae, subkingdom: Tracheobionta, superdivision: Spermatophyta, division: Magnoliophyta, Hindawi Publishing Corporation BioMed Research International Volume 2014, Article ID 213973, 13 pages http://dx.doi.org/10.1155/2014/213973

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Review ArticleMallotus philippinensis Muell Arg (Euphorbiaceae)Ethnopharmacology and Phytochemistry Review

Mayank Gangwar12 R K Goel2 and Gopal Nath1

1 Laboratory of Gastrointestinal Infections and Molecular Diagnosis Department of Microbiology Institute of Medical SciencesBanaras Hindu University Varanasi 221005 India

2Department of Pharmacology Institute of Medical Sciences Banaras Hindu University Varanasi 221005 India

Correspondence should be addressed to Gopal Nath gopalnathgmailcom

Received 15 February 2014 Revised 2 May 2014 Accepted 2 May 2014 Published 8 July 2014

Academic Editor Kota V Ramana

Copyright copy 2014 Mayank Gangwar et al This is an open access article distributed under the Creative Commons AttributionLicense which permits unrestricted use distribution and reproduction in any medium provided the original work is properlycited

Mallotus philippinensisMuell Arg (Euphorbiaceae) are widely distributed perennial shrub or small tree in tropical and subtropicalregion in outer Himalayas regions with an altitude below 1000m and are reported to have wide range of pharmacologicalactivities Mallotus philippinensis species are known to contain different natural compounds mainly phenols diterpenoidssteroids flavonoids cardenolides triterpenoids coumarins isocoumarins and many more especially phenols that is bergeninmallotophilippinens rottlerin and isorottlerin have been isolated identified and reported interesting biological activities suchas antimicrobial antioxidant antiviral cytotoxicity antioxidant anti-inflammatory immunoregulatory activity protein inhibitionagainst cancer cell We have selected all the pharmacological aspects and toxicological and all its biological related studies Thepresent review reveals that Mallotus philippinensis is a valuable source of medicinally important natural molecules and providesconvincing support for its future use in modern medicine However the existing knowledge is very limited about Mallotusphilippinensis and its different parts like steam leaf and fruit Furthermore detailed safety data pertaining to the acute and subacutetoxicity and cardio- and immunotoxicity also needs to be generated for crude extracts or its pure isolated compounds This reviewunderlines the interest to continue the study of this genus of the Euphorbiaceae

1 Introduction

Mallotus (family Euphorbiaceae) is a large genus of treesand shrubs distributed chiefly in the tropical and subtropicalregions of the Old World with around 20 species in India[1]Mallotus philippinensisMuell (commonly called KamalaKampillaka and Kapila and locally known as Shendri) isa very common perennial shrub or small tree found inouter Himalayas ascending to 1500 meters Mature fruitshave glandular hairs collected as reddish brown powderwhich is collected in cloth by shaking and rubbing the fruitsby hand The collected material is fine granular powderdull red or madder red-colored and floats on water Thisplant is traditionally used for antifilarial [2] antibacterialanti-inflammatory and immune-regulatory activity [3] andalso used as purgative anthelmintic vulnerary detergentmaturant carminative alexiteric and is useful in treatment of

bronchitis abdominal diseases spleen enlargement antimi-crobial antiparasitic and so forth (Figure 18)

Some other medicinal plants reported similar anticesto-dal activity shown in Table 1 Somemedicinal plants exportedfrom India are Aconitum species (root) Acorus calamus(rhizome) Adhatoda vasica (whole plant) Berberis aristata(root) Cassia angustifolia (leaf and pod) Colchicum luteum(rhizome and seed) Hedychium spicatum (rhizome) andHeradeum candicans (rhizome) [4]

11 Scientific Classification Consider the following

kingdom Plantaesubkingdom Tracheobiontasuperdivision Spermatophytadivision Magnoliophyta

Hindawi Publishing CorporationBioMed Research InternationalVolume 2014 Article ID 213973 13 pageshttpdxdoiorg1011552014213973

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Table 1 Some medicinal plants reported for the antihelmintic activity

S no Sources Part used Family Reference1 Strobilanthes discolor Leaves Acanthaceae [56]2 Trifolium repens Aerial shoot Fabaceae [57]3 Houttuynia cordataThumb Leaves Piperaceae [58]4 Lasia spinosa Linn Leaves stalk stem Araceae [59]5 Centella asiatica Linn Leaves Apiaceae [60]6 Clerodendrum colebrookianumWalp Leaves Verbenaceae [61]7 Gynura angulosa DC Leaves Asteraceae [61]8 Aloe vera Linn Leaves Liliaceae [61]9 Psidium guajava Linn Leaves Myrtaceae [62]10 Curcuma longa Linn Rhizomes Zingiberaceae [63]11 Ocimum sanctum Linn Oileugenol Lamiaceae [64]12 Albizia anthelmintica Steam bark Mimosaceae [65]13 Berlinia grandiflora Steam bark Leguminosae [66]14 Nicotiana tabacum L leaves Solanaceae [67]15 Calotropis procera (Ait) Ait Flowers Asclepiadaceae [68]

class Magnoliopsidasubclass Rosidaeorder Euphorbialesfamily EuphorbiaceaegenusMallotusspeciesMallotus philippinensis

12 Botanic Description Trees are small to medium-sizedmonoecious in nature up to 25m tall and with a bole upto 50 cm in diameter but usually much less in number(Figure 19(a)) Slash turning deep red Branchlets are reddish-brown glandular

Leaves are alternate and simple more or less leatheryovate to lanceolate cuneate to rounded with two glands atbase Leaves are mostly acute or acuminate at apex conspicu-ously 3-nerved hairy and reddish glandular beneath petiolesize 1ndash4 cm long puberulous and reddish-brown in color(Figure 19(b))Male flowers in terminal and axillary position2ndash10 cm long solitary or fascicled paniculates spikes eachflowers are with numerous stamens small female flowershave spikes or slender racemes each flower with a stellatehairy 3 celled ovary with 3 papillose stigmas Fruit is adepressed-globose 3-lobed capsule 5 7mm and 10mm stel-late puberulous with abundant orange or reddish glandulargranules 3-seeded (Figure 19(d)) Seeds are subglobose andblack in color and 4mm across (Figure 19(e)) [5]

13 Biology In this genusMallotus philippinensis (M philip-pinensis) flowers mature from March to April and fruitsmature in July-August M philippinensis has extra floralnectaries attracting ants

14 Ecology M philippinensis has a widespread natural dis-tribution from the western Himalayas through India SriLanka to southern China and throughout Malesia to Aus-tralia Sometimes it is gregarious butmore usuallymixedwith

other species both in forests and open scrubland Kamalatree is common in evergreen forest especially in secondaryforest and sometimes even dominant in the undergrowthKamala tree withstands considerable shade it is frost-hardyand resistant to drought

15 Biophysical Limits Kamala tree is mostly grown at analtitude of 0ndash1600mat amean annual temperature of 16ndash28∘Cwith mean annual rainfall of 800ndash2000mm Plants will growmostly in a wide range of soil types including infertile soilslimestone acid and rocky land

2 Vernacular Names and Traditional Uses

21 Vernacular Names The vernacular names are as fol-lows English Kamala tree Hindi Kamala Sindur Rohiniand Kambhal Bengali Kamala Kamalagundi GuajaratiKapilo Kannad Kampillaka Kunkumadamara MalayalamSinduri Manjana Kuramatakku Kampipala and PonnagamMarathi Shindur Shendri and Kapila Punjabi KumilaKamal Kambal and Kamela Tamil Kapli KungumamKurangumanjanatti Kamala Manjanai Kunkumam andKamala Telugu Kunkuma Chendra-sinduri Kapila Vassun-tagunda Sundari Vasanta and Kumkumamu ArabicKinbilAssam Gangai Puddum and Lochan Oriya Bosonto-gundiKumala Sundragundi and Kamalagundi Pers Kanbela San-thal Rora

22 Traditional Uses According to Ayurveda leaves arebitter cooling and appetizer All parts of plant like glandsand hairs from the capsules or fruits are used as heat-ing purgative anthelmintic vulnerary detergent maturantcarminative and alexiteric and are useful in treatment ofbronchitis abdominal diseases and spleen enlargement andif taken with milk or curd (yoghurt) it can be quite useful forexpelling tapeworms [6] Kamala or Kampillakah is also usedas an oral contraceptive The powder and a few other parts of

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Table 2 Cardenolide and its derivatives

O

O

O

Me

OH

H

H

HR1

R2

No Name R1 R2 References1 Coroglaucigenin CH2OH H [8]2 Coroglaucigenin L-rhamnoside CH2OH L-rham [8]3 Corotoxigenin CHO H [8]4 Corotoxigenin L-rhamnoside CHO L-rham [8]

Kamala are also used in external applications to promote thehealing of ulcers and woundsThey are used to treat parasiticaffections of the skin like scabies ringworm and herpes

23 Common Adulterants Glandular hair powder of Mphilippinensis is commonly adulterated with Annato dye(Bixa orellana Linn) ferric oxide brick dust and ferruginoussand Casearia tomentosa (stem bark powder) Carthamustinctorius (flower powder) Ficus benghalensis (fruit powder)and Flemingia macrophylla (hairs of fruits) are also reportedto be used as adulterant or substitute of Kampillaka [7]

3 Chemical Constituents

Major phytochemicals present in this genus contain dif-ferent natural compounds mainly phenols diterpenoidssteroids flavonoids cardenolides triterpenoids coumarinisocoumarins and many more to discover Present knowl-edge about this endangered species of medicinal plant isstill limited with respect to its phytochemistry and biologicalactivity However some researchers have contributed towardsisolation of some novel constituents and their activity One ofthe major chemical constituent that is rottlerin ofM philip-pinensis is listed below with its chemical structure and itsmajor biological activities along with other phytochemicals(Figure 18)

31 Cardenolides M philippinensis seeds contain cardeno-lides The seeds of M philippinensis were found to containafter fermentation four cardenolides (Table 2) of whichtwo were newly reported corotoxigenin L-rhamnoside andcorogl-aucigenin L-rhamnoside [8]

32 Triterpenoids Some Mallotus species were found tohave a characteristic feature of pentacyclic triterpenoids witha 66665 ring system The petroleum ether extract of

Table 3 Lupeol and its derivatives

H

H

H

H

CH3

CH3

CH3CH3

CH3

CH2

OR

H3C

H3C

No Name R1 References6 Lupeol-3-acetate Ac [9]7 Lupeol H [9]

AcO

OHH

H

H

HCH3

CH3

CH3CH3

CH2

H3C

H3C

Figure 1 Betulin-3-acetate

HHH

O

CH3

CH3

CH3

CH3

CH3

CH3

CH3

H3C

Figure 2 Friedelin

the heartwood of M philippinensis yielded triterpenoidsbetulin-3-acetate (Figure 1) as a major compound lupeolacetate (Table 3) and lupeol (Table 3) [9] Friedelane-typetriterpenoids are very common inMallotus species Friedelin(Figure 2) was obtained from the stem bark of M philip-pinensis [10] Most of the genera of family Euphorbiaceaesuch as Drypetes [11] or Celaenodendron [12] also containfriedelin in rich amount Friedelin is common and is alsofound in plants from other orders Other known pentacyclicterpenoids that is acetylaleuritolic acid (Figure 3) found tobe reported in the petroleum and ether extracts from barkof M philippinensis [9] The first olean-18-ene triterpeneoxidized at C-22 (Figure 4) was isolated from the stem bark

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AcOH

H

H

CH3

CO2H

H3C

H3C

CH3 CH3

CH3

CH3

Figure 3 Acetylaleuritolic acid or aleuritic acid acetate

H

H

H

O

O

OH

CH3

CH3

CH3 CH3

CH3

CH3

H3C

H3C

H3C

Figure 4 3b-Acetoxy-22b-hydroxyolean-18-ene

of M Philippinensis [10] Apart from above triterpeniodsursane-type triterpenoid a-amyrin (Figure 5) reported fromthe petroleum ether and ethereal extracts ofM philippinensisbark [9]

33 Steroids Common steroid b-sitosterol (Figure 6) wasisolated from petroleum ether extracts of the heartwood andbark ofM philippinensis [9] Daucosterol was obtained fromether extract from bark ofM philippinensis [9]

34 Phenolic Compounds Isocoumarins Bergenin(Figure 7) an isocoumarin was isolated in 1972 fromthe heartwood ofM philippinensis This compound was alsoobtained from the bark and the leaves of M philippinensis[9]

Two new chalcone derivatives (flavonoids) kamalachal-cones A and B (Figures 8-9) with a unique ring systemcaused by dimerization between a dimethylchromene ringand a phenoxyl group were isolated from kamala (Mphilippinensis) [13] Three other novel chalcone derivativesmallotophilippens C D and E (Figures 10 11 12 13 and 14)were isolated from the fruits ofM philippinensis [14] lignanschalcones and dimeric chalcone derivatives [15]

Four phloroglucinol derivatives (kamalins) rottlerin andisorallorottlerin (Figures 15 and 16) were isolated from Mphilippinensis [16] Isorottlerin (Figure 17) was also men-tioned inM philippinensis [17]

Fruit and bark of plant contain condensed tanninsresponsible for antioxidant activity Methanolic bark extract

H

H

H

HO

CH3

CH3

CH3

CH3

CH3CH3

H3C

H3C

Figure 5 120572-Amyrin

H

H

H

H

OR

CH3

CH3

H3Ci-Pr

Et

Figure 6 120573-Sitosterol

OH

OHOH

OH

HO

MeO

O

O

O

Figure 7 Bergenin

O

O

O

O O

CH3

CH3

CH3

CH3

H3C

H3C

H

H

HHO

HO OH

Figure 8 Kamalachalcone A

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O

O

O

O

O O

CH2

CH3

CH3

CH3

CH3

H3C

H3C

H3C

H

H

H

HO

HO

HO

HO OH

OH

Figure 9 Kamalachalcone B

O O

OOH

OHOH

HO HO 2

3

45

6

78

9

10

1112

1314

15

1998400

2998400

3998400

4998400

5998400

6998400

7998400

8998400

Figure 10 Mallotophilippen A or 1-[57-dihydroxy-22-dimethyl-6-(246-trihydroxy-3-isobutyryl-5-methyl-benzyl)-2H-chromen-8-yl]-2-methyl-butan-1-one

of M philippinensis subjected to characterization throughcolumn chromatography on a Sephadex LH-20 column usingethanol and acetone-water as the mobile phases tanninsand phenols were quantified Bark extract contains 541mggof total phenolics and infractions ranging from 54mgg(fraction I) to 927mgg (fraction VI) and condensed tanninswere detected in fractions IIndashVI [18 19] In 1989 leaves ofM philippinensis were reported for tannins and other relatedcompounds by Saijo et al [20]

35 Other Compounds Unsaturated fatty acids that is triply-unsatured hydroxy acid kamlolenic acid different fatty acidsand glyceride [21] have been reported from Kamala (Mphilippinensis) seed oil

Resinous coloured material contains active parts of rott-lerin and isorottlerin It also contains homorottlerine red role50 yellow role 5 manure 2 volatile oils tannin gumcitric acid and oxalic acid

4 Pharmacological Activities

41 Antifilarial Activity The effect of aqueous and alcoholicleave extracts of M philippinensis (Lam) Muell was studiedon the spontaneous movements of the whole worm and

O O

OOH

OHOH

HO HO 2

3

45

6

78

9

10

1112

1314

15

1998400

2998400

3998400

4998400

5998400

6998400

7998400

Figure 11 Mallotophilippen B or 1-[6-(3-acetyl-246-trihydroxy-5-methyl-benzyl)-57-dihydroxy-22-dimethyl-2H-chromen-8-yl]-2-methyl-butan-1-one

OH

OH

HO

OHO

Figure 12 Mallotophilippen C or (1-[6-(37-dimethyl-octa-26-dienyl)-57-dihydroxy-22-dimoethyl-2H-chromen-8-yl]-3-(4-hy-droxy-phenyl)-propenone) R = H

OH

OH

OHO

OHO

Figure 13 Mallotophilippen D or 3-(34-dihydroxy-phenyl)-1-[6-(37-dimethyl-octa-26-dienyl)-57-dihydroxy-22-dimethyl-2H-chromen-8-yl]-propenone R = OH

nerve-muscle (nm) preparation of Setaria cervi and on thesurvival of microfilariae in vitro Both the extracts result ininhibition of spontaneous motility of whole worm and thenm preparation of S cervi characterized by initial stimula-tion followed by depression in amplitude The tone and rateof contractions remained visibly unaffected Aqueous extractat higher concentration showed immediate reduction in toneThe concentration required to inhibit the movements of nmpreparation was 15th for aqueous and 111th for alcoholicextract compared to that for the whole worm suggesting acuticular permeability barrier The stimulatory response ofacetylcholine was blocked by aqueous extract onwhole worm

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OH

OH

OH

O

OHO

Figure 14 Mallotophilippen E or 1-[57-dihydroxy-2-methyl-6-(3-methyl-but-2-enyl)-2-(4-methyl-pent-3-enyl)-2H-chromen-8-yl]-3-(34-dihydroxy-phenyl)-propenone

OH

OH

OHOH

O

O

O

HO

Figure 15 Rottlerin

movements On the microfilariae the LC50and LC

90were 18

and 20 ngmL for aqueous and 12 and 15 ngmL for alcoholicextracts respectively [2] Further study will be required toevaluate the same activity with its phytochemicals

42 Antifertility Activity Seeds extract of M philippinensisexhibits adverse effects on different reproductive parametersof female rats According to the study extract reducesserum FSH and LH levels probably by affecting hypotha-lamicpituitary axis in experimental animals This reducedlevel may affect follicular development quality of ovulatedeggs corpus luteum formation estrus cycle andmaintenanceof pregnancy in rats [22] This antifertility effect of plantextract is supposed to be caused by rottlerin (Figure 15) aphloroglucinol derivative Acetyl rottlerin may be active butisorottlerin (Figure 17) is either inactive or slightly active [23]Effect of pure rottlerin can be further studied so as to clarifythe potential of phloroglucinol derivatives

43 Antibacterial and Antifungal Activity A series of 61Indian medicinal plants belonging to 33 different familiesused in various infectious disorders were screened for theirantimicrobial properties Screening was carried out at 1000and 500 120583gmL concentrations by agar dilution methodagainst Bacillus cereus varmycoides Bacillus pumilus Bacillussubtilis Bordetella bronchisepticaMicrococcus Luteus Staphy-lococcus aureus Staphylococcus epidermidis Escherichia coli

OH

OH

O

O

O

HO

HO

HO

Figure 16 Isoallorottlerin

OH

OH

O

O

O

OHO

HO

Figure 17 Isorottlerin

Klebsiella pneumonia Candida albicans and Saccharomycescerevisiae Twenty-eight plant extracts showed activity againstat least one of the test organisms used in the screeningOn the basis of the results obtained study concludes thatthe crude extracts of M philippinensis exhibited significantantimicrobial activity [3] and properties that support folk-loric use in the treatment of some diseases as broad-spectrumantimicrobial agents Steam bark of plant and its chloroformfractions and the methanolic extract significantly inhibitthe pathogenic bacteria with significant zones of inhibitioncomparable to the standard drug used However the hexanicextract did not show any significant activity [24] Glandularhair of fruits of Mallotus exhibits significant antibacterialactivity against human pathogenic bacteria withMIC ranging15ndash20mgmL This extract does not show any inhibitionagainst different species of candida This shows that fruitextract possesses antibacterial activity without any antifungalpotential The results of the study may justify the use of theplant against bacterial pathogens This probably explains theuse of these plants by the indigenous people against a numberof infections [25]

However ethanolic extract shows potent anti-Heli-cobacter pylori activity at the concentration of 156ndash312mgLagainst eight H pylori strains Further purification of extractrevealed that rottlerin exhibits potent bactericidal effectwith minimal bactericidal concentration (MBC) of 312ndash625mgL against different resistant strains of clarithromycin

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M philippinensis

Rottlerin

Fruit

H3C

HO

HO

OH OH

OH

O

O

O

CH3

CH3

CH3

Antifertility

Antimicrobial

Protein inhibition

Antituberculosis activity

Antiallergic activity

Antiproliferative activity

Antiparasitic (cestodal)

Figure 18 Rottlerin and its major biological activities

and metronidazole including Japanese and Pakistani strains[17]

44 Anti-Inflammatory and Immunoregulatory ActivityChalcones derivatives from the fruits of M philippinensisand mallotophilippens C D and E (Figures 12 13 and14) inhibit nitric oxide (NO) production and inducibleNO synthase (iNOS) gene expression by a murinemacrophage-like cell line (RAW 2647) which was activatedby lipopolysaccharide (LPS) and recombinant mouseinterferon-gamma (IFN-gamma) Further investigationssuggest the downregulation of cyclooxygenase-2 geneinterleukin-6 gene and interleukin-1b gene expressionThe above results show that these chalcones have goodanti-inflammatory and immunoregulatory effects [26]

45 Antioxidant Activity and Antiradical Activity Differentfractions of bark and fruit of Mallotus were studied forits total antioxidant activity (TAA) and antiradical activityagainst DPPH on a Sephadex LH-20 column using ethanoland acetone-water asmobile phase Among different extractsbark fraction showed the strongest antiradical activity (TAAvaluemdash527 mmol Trolox equivg) and reducing powerAnother extract that is phenolic fraction shows TAAranging from 058mmol Troloxg (fraction I) to 682mmolTroloxg (fraction IV) this is the strongest fraction showingantiradical activity against DPPH and reducing power TAAof other extracts ranged from 005 to 179mmol Troloxequivg [18 19]

46 Protein Inhibition Implicated in Cancer Processes Proteinkinase is inhibited with some specificity for PKC by rottlerina compound isolated from Mallotus Inhibition of PKCappears due to a strong competition between rottlerin andATP CaM-kinase III is suppressed by rottlerin as effectivelyas PKC 120575 among different protein kinases tested Novelinhibition property and improved selectivity for a distinctPKC isoenzyme of rottlerin are suggestive from its chemicalstructure [27 28] Rottlerin is also very potent in blockingother kinases including AktPKB and p38 MAPK [29ndash31] Italso inhibits human T cell responses [32] reduces MUC5ACexpression in human epithelial cells [33] abrogates reactiveoxygen species production in hepatic stellate cells [34] andprevents histamine-induced H1-receptor gene expression inHeLa cells [35] However still very limited information isavailable of rottlerin towards cancer disease and its mecha-nism of action

47 Hepatoprotective Activity Methanolic extract of Mphilippinensis leaves decreases the CCl

4-induced elevation in

biochemical parameters (SGOT SGPT SALP direct biliru-bin total bilirubin andMDA) on pretreatment at doses 100ndash200mgkg and also reversed the functional and antioxidantparameters This study suggests that leave extract was effec-tive in functional improvement of hepatocytes Histopatho-logical studies also suggest the hepatoprotective activity ofplant [36]

48 In Vitro Cytotoxicity against Human Cancel Cell Glan-dular hair extract of Mallotus fruit powder was assayed

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(a) (b)

(c) (d)

(e)

Figure 19 Mallotus philippinensis (a) Mature plant (b) leaf (c) initial inflorescence of seed setting (d) mature fruits twig (e) mature fruitwith seed

against 14 human cancer cell lines among different fractions95 ethanolic extract showed the highest cytotoxic effect ascompared to 50 ethanolic and aqueous portion Furtherthe chromatographic analysis of the said fraction afforded apolyphenolic molecule rottlerin inMallotus plant [37]

49 Anticestodal ActivityVeterinary Applications M philip-pinensis fruit was found to be very effective against gas-trointestinal cestodes in Beetal goats and other ruminantsComparative anticestodal efficacies of single oral dose treat-ments with the powdered fruit ofM philippinensis (125 250and 375mgkg) its water or methanol extracts (equivalent to375mgkg) and the total glycosides (25 50 and 100mgkg)were determined in naturally cestode-infected Beetal goats[38] An ethnobotanical survey has been conducted foranthelmintics in ruminants so as to document the plantsused to treat and control helminthes Mallotus has beenfrequently used to treat helminthosis in ruminants [39] M

philippinensis fruit extract of 800mgkg twice daily for 3days was observed to have curative efficacy against matureadult worms of Hymenolepis diminuta The total follow-upperiod of 90 days did not show any further excretion of eggsin the faeces of treated rats Praziquantel at the dosage of5mgkg also produced a similar effect [40] In vitro scolicidalactivity ofM philippinensis (Lam)Muell Arg fruit glandularhair extract against hydatid cyst Echinococcus granulosusprotoscoleces at concentrations 10 and 20mgmL shows themortality rate 97 to 99 respectively for 60min treatmentwhile up to 93 mortality was observed with 20mgmLfor only 10min treatment This proves that the extract hassignificant scolicidal activity with almost no associated sideeffects [41] In vivo animal model experiment will be furtherrequired to prove its effect against Hydatid cyst

410 Purgative Activity and Anthelmintic Activity A signifi-cant purgative effect after an oral dose (120mgkg) in rats was

BioMed Research International 9

assessed from resins isolated from plant Its effect was evalu-ated from the weight of faeces as well as from surface areaof blotting paper soaked by liquid faeces The anthelminticeffect on tape worm was evaluated in albino rates fromthe resin of the plant showed lethal effect of 3569 and7821 respectively in small intestine in concentrations 60and 120mgkg respectively [42 43]

411 Antituberculosis Activity Organic extract of plant afterbioassay-directed fractionation yields five compounds themost active of which againstMycobacterium tuberculosis wasa new compound 8-cinnamoyl-57-dihydroxy-22-dimethyl-6-geranylchromene for which the name mallotophilippenF is suggested The second compound 8-cinnamoyl-22-dimethyl-7-hydroxy-5-methoxychromene was isolated froma natural source for the first time while the remaining threecompounds rottlerin isoallorottlerin or isorottlerin andthe so-called ldquored compoundrdquo 8-cinnamoyl-57-dihydroxy-226-trimethylchromene had been already isolated fromthis plant Isolated compounds were identified by 2D-NMRand C-13 NMR [44] Ethanolic extract of plant was assayedfor antimycobacterial activity against M smegmatis by discdiffusion assay Further antituberculosis potential of leavesextract was identified by radiometric BACTEC assay resultrevealed that ethanolic extract ofM philippensis showed anti-tuberculosis activity against virulent and avirulent strains ofM tuberculosis H37Rv andM tuberculosis H37Ra with min-imum inhibitory concentrations of 025 and 0125mgmLminus1respectively The inhibition in growth index values of Mtuberculosis was observed in the presence of ethyl acetatefraction at a minimum concentration of 005mgmLminus1 Itsuggests that ethanolic and ethyl acetate fraction of plantpossesses significant antimycobacterial activity [45] Steambark of M philippinensis has also been reported for itsantitumor promoting effect which was due to the presenceof 3120572-Hydroxy-DA-friedooleanan-2-one [46]

412 Antiallergic Activity M philippinensis fruit containstwo new phloroglucinol derivatives mallotophilippensA and B (Figures 10 and 11) which were identified usingchemical and spectral data as 1-[57-dihydroxy-22-di-methyl-6-(246-trihydroxy-3-isobutyryl-5-methyl-benzyl)-2H-chromen-8-yl]-2-methyl-butan-1-one and 1-[6-(3-Acetyl-246-trihydroxy-5-methyl-benzyl)-57-dihydroxy-22-dim-ethyl-2H-chromen-8-yl]-2-methyl-butan-1-one respe-ctively These compounds inhibited the production ofnitric oxide (NO) and inducible NO synthase (iNOS) geneexpression by a murine macrophage-like cell line (RAW2647) which was activated by lipopolysaccharide (LPS)and recombinant mouse interferon-g (IFN-g) Furtherphloroglucinol derivatives inhibit histamine release from ratperitoneal mast cells induced by compound 4880This studysuggests its anti-inflammatory activity [47] Rottlerin hasbeen tested in animal models of IgE-dependent anaphylaxisand the antiallergic mechanisms of action in mast cellsAntiallergic action of rottlerin has been tested in passivecutaneous anaphylaxis and passive systemic anaphylaxismouse models and in anaphylactic contraction of bronchial

rings isolated from sensitized guinea pigs This experimentsproves antiallergic effect of rottlerin by blocking IgE-inducedmast cell degranulation This report suggests the use ofrottlerin in mast cell-mediated allergic disorders includingurticaria and allergic asthma [48]

413 Anti-Leukaemic Activity Root extract ofM philippinen-sis was tested on human promyelocytic leukemia HL-60 cellproliferation cell cycle regulators and apoptosis in order toinvestigate its antileukemic effect Hexane fraction showedpromising toxicity against p53-deficient HL-60 cells (IC

50

15mg dry roots equivalentmL medium) after 72 h andinterestingly inhibition of cell proliferation was preceded bythe upregulation of the protooncogenes Cdc25A and cyclinD1 within 24 hours suggesting its antileukemic effect inHL-60 cells After isolation and identification by GC-MSpolyphenols were the main compounds of the hexane extractthat inhibited proliferation and induced apoptosis [49]

414 Antiproliferative Activity Antiproliferative effect wasevaluated against Thp-1 cell lines from the isolated com-pounds of M philippinensis fruit extract in which 41015840-hydroxyrottlerin showed 54 growth inhibition ofThp-1 cellline [50] Other isolated compounds were also tested againstdifferent fungi andwere found to be very effective IC

50values

415 Anti-HIV Activity Four phloroglucinol derivativesnamed mallotophenone (5-methylene-bis-26-dihydroxy-3-methyl-4-methoxyacetophenone) mallotochromene (8-acetyl-57-dihydroxy-6-(3-acetyl-24-dihydroxy-5-methyl-6-methoxybenzyl)-22-dimethylchromene) mallotojaponin(3-(33(dimethylallyl) S-(3(acetyl-24-dihydroxy-5-methyl-6-methoxybenzyl)-phloracetophenone) andmallotolerin (3-(3-methyl-2-hydroxybut-3-enyl)-5-(3-acetyl-24-dihydroxy-5-methyl-6-methoxybenzyl)-phloracetophenone) weretested for their ability to inhibit the activity of humanimmunodeficiency virus- (HIV-) reverse transcriptaseThe mode of inhibition of mallotojaponin was foundto be competitive with respect to the template primer(rA)n (dT)12ndash18 and noncompetitive with respect to thetriphosphate substrate dTTPThe Ki value of mallotojaponinfor HIV-reverse transcriptase was determined to be 61 120583M[51]

416 Antitumor Activity Four known friedelane-type trit-erpenoids friedelin 3-hydroxy-DA-friedoolean-3-en-2-one 2120573-hydroxy-DA-friedooleanan-3-one and 3120572-hy-droxy-DA-friedooleanan-2-one and two known lupane-type triterpenoids lupeol and betulin were isolated fromthe stem bark of M philippinensis and were tested fortheir inhibitory effects on Epstein-Barr virus early antigen(EBV-EA) activation induced by 12-O-tetradecanoylphorbol13-acetate (TPA) The inhibitory effect of compounds 2(IC50

= 292mol ratio32 pmolTPA) and 4 (IC50

= 288) wasstronger than those of the other compounds tested and thepositive control curcumin (IC

50= 343) Compound 3120572-

hydroxy-DA-friedooleanan-2-one strongly inhibited mouse

10 BioMed Research International

skin tumor promotion in an in vivo two-stage carcinogenesismodel [46]

417 Wound Healing and Mesenchymal Stem Cell (MSC)Proliferation Bark extract ofMallotus philippinensis has beentested in vitro for wound healing activity by examining theproliferation and migration of MSCs KUM6 cells prolifer-ation and migration have been enhanced at 016ndash4 120583gmLand unregulated the activity of MSCs by secreting variouscytokines to wounded site from bone marrow to systemiccirculation and finally remodel wounded tissues [52]

418 Toxicities Seeds of M philippinensis ethereal extracthave adverse effect on various parameters of female rats Eventhe extract reduces serum levels of gonadotropins in treatedanimals at high dose of 100mgkg body weight Reducedweights of ovary and uterus follicular development andincreased atretic follicular in the ovary are due to subnormallevels of steroid hormones Thus pregnancy is very difficultin female rats treated with kamala seed extract [22]

419 Colouring Agent-Dye Glandular hairs of fruit aremostly used as an orange dye for silk [53 54]

5 Pharmacognostic Evaluation ofMallotus philippinensis

Morphological study shows that fruit depresses globoseand is three-lobed capsule 5ndash7mm times 8ndash10ndash12mm stellate-puberulose and with abundant orange or reddish glan-dular granules Seeds are subglobose and black in colorOrganoleptic property of the red fruit shows that it is tastelessand odourless Microscopic description showed the presenceof epicarp which contained a compactly packed layer ofmucilaginous cells and mesocarp composed of columnarcells which are closely arranged Its polygonal cells are com-pactly arranged in 2-3 layers Presence of lignified vasculararrangement has been observed in the transverse section [55]

6 Conclusion and Future Perspective

Medicinal plants have been clinically used and its interest hasbeen dramatically increased over the past decades throughoutthe world and its formulations are increasingly cited inmedia Daily consumption of the natural products and theirformulations by an extensive number of patients lead toserious concern for scientist to study its efficacy and safetyBecause of extensive use and its benefits natural productsin many countries are regulated both as medicinal productsand as food supplements often labeled as natural foodsupplements

Traditional use and its growing demand for Mallotusphilippinensis and its other species lead to compile this reviewand commented on the current knowledge provided byclinical and preclinical research on the effect of this plant

Mallotus philippinensis has been widely used as tradi-tional medicine in several parts of countries including IndiaEvery part of this plant possesses its specific medicinal prop-erties and is usedmainly in ayurveda to fight against intestinalworms in domestic and grazing animals when administeredwith jaggeryHowever only a few reports are attributed to thisplant and its different parts and there is a large scope for inves-tigation Hence it is required to explore more of its potentialwithin the field of medicinal and pharmaceutical sciences fornovel and fruitful application of this plant in form of naturalformulation Along with this medicinal importance thisplant is used against human pathogens including H pylorianti-inflammatory activity antioxidant antiradical proteininhibition hepatoprotective antiallergic anti-HIV activityand many more Phytochemical investigation revealed that alarge number phenol derivatives and several miscellaneouscompounds from different classes have been isolated fromthis species The phenols diterpenoids steroids flavonoidscardenolides triterpenoids coumarins and isocoumarinsare mostly distributed in all parts of the plant The othermajor isolated pure compounds from this species mostlybelong to phenolic group exhibiting most of the biologicalactivity Various types of extracts from different parts andsingle compounds derived from this species have beenfound to possess biological activities including antioxidantantimicrobial anti-inflammatory cytotoxicity and immunemodulatory Fruit and bark of plant contain condensed tan-nins responsible for antioxidant activity Somenovel chalconederivatives mallotophilippens C D and E were isolatedfrom the fruits of M philippinensis Mallotoxin or rottlerinhas great anticancerous potential Among the ever-anticanceragents rottlerin appears to have great potentiality for beingused in chemotherapy Rottlerin will become a potentialmolecule for research in future to treat cancerous cell as itwill affect cell machineries involved in apoptosis survivaland autophage This suggests the view that this species haspotential to be a beneficial chemotherapeutic remedy

Although the data and other reports provided that thismedicinal plant is of great biological use in different phar-macological activities including anticancer further researchis needed in different areas regarding the toxicity and efficacyof pure phytochemicals isolated from different parts of thisplant More data will be needed from preclinical and clinicalstudies on humans to clarify its potency and safety aslack of knowledge with respect to its adverse effects andmethodological accuracy in the literature limits towardsits standardized formulation Furthermore the mechanismof action of the phytochemicals and extract of Mallotusphilippinensis is unclear more exhaustive studies will beperformed to explore its mechanism and structure activityrelationship among various constituents

In conclusion this review confirms the great potential ofMallotus philippinensis As very limited information is stillknown for this species it leads us to continue the study ondifferent species of Mallotus plant and its interesting phar-macological properties Further natural product chemistryof isolated moiety and its structural analysis of compounds

BioMed Research International 11

responsible for these activities will be an interesting field ofresearch

Conflict of Interests

The authors declare that there is no conflict of interests re-garding the publication of this paper

Acknowledgment

The authors gratefully acknowledge the financial supportprovided by CSIR Government of India New Delhi forawarding SRF in the form of research fellowship

References

[1] C-J Widen and H S Puri ldquoNatural occurrence and chemicalvariability of phloroglucinols inKamalardquoPlantaMedica vol 40no 3 pp 284ndash287 1980

[2] R Singh K C Singhal and N U Khan ldquoAntifilarial activity ofMallotus philippinensisLam on Setaria cervie (Nematoda Filar-ioidea) in-vitrordquo Indian Journal of Physiology andPharmacologyvol 41 no 4 pp 397ndash403 1997

[3] V P Kumar N S Chauhan H Padh and M Rajani ldquoSearchfor antibacterial and antifungal agents from selected Indianmedicinal plantsrdquo Journal of Ethnopharmacology vol 107 no2 pp 182ndash188 2006

[4] S Shrikumar and T K Ravi ldquoApproaches towards developmentand promotion of herbal drugsrdquo Pharmaceutical Reviews vol 1no 1 pp 180ndash183 2007

[5] C Orwa A Mutua and R Kindt ldquoAgroforestree Database atree reference and selection guiderdquo Version 4 0 2009

[6] K Usmanghani A Saeed and M T Alam ldquoIndusynicMedicine Karachirdquo Research Institute of Indusyunic Medicinevol 1997 pp 285ndash287 1997

[7] F Ahmad and S Hashmi ldquoAdulteration in commercial Kamila(Mallotus philippinensisMuell) an anthelmintic drug of reputerdquoHamdard Medicus vol 38 pp 62ndash67 1995

[8] K D Roberts E Weiss and T Reichstein ldquoGlycosides andaglycons CCLII Cardenolides of the seed of Mallotus philip-pinensisrdquo Helvetica Chimica Acta vol 46 pp 2886ndash2893 1963

[9] M Bandopadhyay V K Dhingra and S K Mukerjee ldquoTriter-penoid and other components of Mallotus philippinensisrdquo Phy-tochemistry vol 11 no 4 p 1511 1972

[10] S P Nair and J Madhusudana Rao ldquoKamaladiol-3-acetate fromthe stem bark of Mallotus philippinensisrdquo Phytochemistry vol32 pp 407ndash409 1993

[11] J DWansi JWandjiW A Kamdem et al ldquoTriterpenoids fromDrypetes chevalieri Beille (Euphorbiaceae)rdquo Natural ProductResearch vol 20 no 6 pp 586ndash592 2006

[12] P Castenada A Bahena and E Garcia ldquoChemical studieson Mexican plants used in traditional medicine XXIX Sec-ondary metabolites from the stem bark of Celaeno-dendronmexicanumrdquo Journal of Natural Products vol 56 pp 1575ndash15791993

[13] T Tanaka T Ito M Iinuma Y Takahashi and H NaganawaldquoDimeric chalcone derivatives from Mallotus philippinensisrdquoPhytochemistry vol 48 no 8 pp 1423ndash1427 1998

[14] T M Nguyen V M Chau V K Phan et al ldquoStudy on chemicalconstituents of the leaves of Mallotus philippinensisrdquo Tap ChiHoa Hoc vol 48 pp 352ndash357 2010

[15] M Furusawa Y Ido T Tanaka et al ldquoNovel complex flavonoidsfrom Mallotus philippinensis (Kamala tree)rdquo Helvetica ChimicaActa vol 88 no 5 pp 1048ndash1058 2005

[16] M Lounasmaa C J Widen C M Tuuf and A HuhtikangasldquoOn the phloroglucinol derivatives of Mallotus philippinensisrdquoPlanta Medica vol 28 no 1 pp 16ndash31 1975

[17] S F H Zaidi I Yoshida F Butt et al ldquoPotent bactericidal con-stituents from Mallotus philippinensis against clarithromycinand metronidazole resistant strains of Japanese and Pakistanihelicobacter pylorirdquo Biological and Pharmaceutical Bulletin vol32 no 4 pp 631ndash636 2009

[18] M Arfan H Amin M Karamac et al ldquoAntioxidant activityof extracts of Mallotus philippinensis fruit and barkrdquo Journal ofFood Lipids vol 14 no 3 pp 280ndash297 2007

[19] M Arfan K Hazrat and K Magdalena ldquoAntioxidant activityof phenolic fractions of Mallotus philippinensis bark extractrdquoJournal of Food Science vol 27 no 2 pp 109ndash117 2009

[20] R Saijo G Nonaka and I Nishioka ldquoTannins and related com-pounds LXXXVIII Isolation and characterization of hydrolyz-able tannins fromMallotus japonicus (Thunb)Mueller-Arg andM philippinensis (Lam)Mueller-ArgrdquoChemical amp Pharmaceu-tical Bulletin vol 37 no 11 pp 2940ndash2947 1989

[21] S C Gupta S S Gupta and J S Aggarwal ldquoChemical exami-nation of the seeds of Mallotus philippinensis III Constitutionof kamlolenic acid isolated from the oilrdquo Journal of Scientific ampIndustrial Research vol 12 pp 240ndash242 1953

[22] S C Thakur S S Thakur S K Chaube and S P Singh ldquoAnetheral extract of Kamala (Mallotus philippinensis (Moll Arg)Lam) seed induce adverse effects on reproductive parametersof female ratsrdquo Reproductive Toxicology vol 20 no 1 pp 149ndash156 2005

[23] M L Gujral D R Varma K N Sareen and A K Roy ldquoOralcontraceptives II Antifertility effect ofMallotus philippinensisrdquoIndian Journal of Medical Research vol 48 pp 52ndash58 1960

[24] KMoorthy K Srinivasan C Subramanian CMohanasundariand M Palaniswamy ldquoPhyto-chemical screening and antibac-terial evaluation of stem bark of Mallotus philippinensis varTomentosusrdquoAfrican Journal of Biotechnology vol 6 no 13 pp1521ndash1523 2007

[25] M Gangwar D Kumar R Tilak et al ldquoQualitative phy-tochemical characterization and antibacterial evaluation ofglandular hairs ofMallotus philippinensis fruit extractrdquo Journalof Pharmacy Research vol 4 no 11 pp 4214ndash4216 2011

[26] A Daikonya S Katsuki and S Kitanaka ldquoAntiallergic agentsfrom naturalsources 9 Inhibition of nitric oxide productionby novel chalcone derivatives from Mallotus philippinensis(Euphorbiaceae)rdquo Chemical amp Pharmaceutical Bulletin vol 52no 11 pp 1326ndash1329 2004

[27] M Gschwendt H J Muller K Kielbassa et al ldquoRottlerina novel protein kinase inhibitorrdquo Biochemical and BiophysicalResearch Communications vol 199 no 1 pp 93ndash98 1994

[28] Y F Liao Y C Hung W H Chang et al ldquoThe PKC deltainhibitor rottlerin induces apoptosis of haematopoietic celllines through mitochondrial membrane depolarization andcaspasescascaderdquo Life Sciences vol 77 no 6 pp 707ndash719 2005

[29] H S Kang E K Park K H Kim et al ldquoReceptor activatorof nuclear factor-kappa B is induced by a rottlerin-sensitiveand p38 MAP kinase-dependent pathway during monocytedifferentiationrdquoMolecules and Cells vol 17 no 3 pp 438ndash4452004

12 BioMed Research International

[30] S P Soltoff ldquoRottlerin an inappropriate and ineffectiveinhibitor of PKC120575rdquo Trends in Pharmacological Sciences vol 28no 9 pp 453ndash458 2007

[31] Y Choi D K Kim S S Kang J K Sonn and E J Jin ldquoIntegrinsignaling and cell spreading alterations by rottlerin treatment ofchick limb bud mesenchymal cellsrdquo Biochimie vol 91 no 5 pp624ndash631 2009

[32] C Springael S Thomas S Rahmouni et al ldquoRottlerin inhibitshuman T cell responsesrdquo Biochemical Pharmacology vol 73 no4 pp 515ndash525 2007

[33] J H Choi Y P Hwang E H Han et al ldquoInhibition of acrolein-stimulated MUC5AC expression by Platycodon grandiflorumroot-derived saponin in A549 cellsrdquo Food and Chemical Toxi-cology vol 49 no 9 pp 2157ndash2166 2011

[34] E L M Guimaraes C Empsen A Geerts and L A vanGrunsven ldquoAdvanced glycation end products induce produc-tion of reactive oxygen species via the activation of NADPHoxidase in murine hepatic stellate cellsrdquo Journal of Hepatologyvol 52 no 3 pp 389ndash397 2010

[35] H Mizuguchi T Terao M Kitai et al ldquoInvolvement of pro-tein kinase C120575extracellular signal-regulated kinasepoly(ADP-ribose) polymerase-1 (PARP-1) signaling pathway in histamine-induced up-regulation of histamine H1 receptor gene expres-sion in HeLa cellsrdquo Journal of Biological Chemistry vol 286 no35 pp 30542ndash30551 2011

[36] S Ramakrishna K M Geetha P V V S Bhaskar gopalR P Kumar C P Madav and L Umachandar ldquoEffect ofMallotus PhilippinensisMuell-Arg leaves against hepatotoxicityof Carbon tetrachloride in ratsrdquo International Journal of Phar-maceutical Sciences and Research vol 2 pp 74ndash83 2011

[37] V Sharma ldquoA polyphenolic compound rottlerin demonstratessignificant in vitro cytotoxicity against human cancer celllines isolation and characterization from the fruits ofMallotusphilippinensisrdquo Journal of Plant Biochemistry and Biotechnologyvol 20 no 2 pp 190ndash195 2011

[38] M S Akhtar and I Ahmad ldquoComparative efficacy of Mallotusphilippinensis fruit (Kamala) or Nilzan drug against gastroin-testinal cestodes in Beetal goatsrdquo Small Ruminant Research vol8 no 1-2 pp 121ndash128 1992

[39] A Jabbar M A Raza Z Iqbal and M N Khan ldquoAn inventoryof the ethnobotanicals used as anthelmintics in the southernPunjab (Pakistan)rdquo Journal of Ethnopharmacology vol 108 no1 pp 152ndash154 2006

[40] M Gangwar A Dalai A Chaudhary et al ldquoStudy on activityof alcoholic extract of glands and hairs of fruits of Mallotusphilippinensis in murine cestodal infection modelrdquo Interna-tional Journal of Pharmacy amp Pharmaceutical Sciences vol 4no 1 pp 643ndash645 2012

[41] M Gangwar V C Verma T D Singh S K Singh R KGoel and G Nath ldquoIn-vitro scolicidal activity of Mallotusphilippinensis (Lam) Muell Arg fruit glandular hair extractagainst hydatid cyst Echinococcus granulosusrdquo Asian PacificJournal of Tropical Medicine vol 6 no 8 pp 595ndash601 2013

[42] S S Gupta P Verma and K Hishikar ldquoPurgative andanthelmintic effects of Mallotus philippinensis in rats againsttape wormrdquo Indian Journal of Physiology amp Pharmacology vol28 no 1 pp 63ndash66 1984

[43] A Hussain M N Khan Z Iqbal and M S Sajid ldquoAn accountof the botanical anthelmintics used in traditional veterinarypractices in Sahiwal district of Punjab Pakistanrdquo Journal ofEthnopharmacology vol 119 no 1 pp 185ndash190 2008

[44] Q Hong D E Minter S G Franzblau M Arfan H Amin andM G Reinecke ldquoAnti-tuberculosis compounds from Mallotusphilippinensisrdquo Natural Product Communications vol 5 no 2pp 211ndash217 2010

[45] V K Gupta C Shukla G R S Bisht D Saikia S Kumarand R L Thakur ldquoDetection of anti-tuberculosis activity insome folklore plants by radiometric BACTEC assayrdquo Letters inApplied Microbiology vol 52 no 1 pp 33ndash40 2011

[46] R Tanaka T Nakata C Yamaguchi S Wada T Yamadaand H Tokuda ldquoPotential anti-tumor-promoting activity of3120572-Hydroxy-D a-friedooleanan-2-one from the stem bark ofMallotus philippinensisrdquo Planta Medica vol 74 no 4 pp 413ndash416 2008

[47] A Daikonya S Katsuki J B Wu and S Kitanaka ldquoAnti-allergic agents from natural sources (4) anti-allergic activityof new phloroglucinol derivatives from Mallotus philippinensis(Euphorbiaceae)rdquo Chemical and Pharmaceutical Bulletin vol50 no 12 pp 1566ndash1569 2002

[48] T K Chan S W David C Cheng S P Guan H MKoh and W S Wong ldquoAnti-allergic actions of rottlerin fromMallotus philippinensisis in experimental mast cell-mediatedanaphylactic modelsrdquo Phytomedicine vol 20 no 10 pp 853ndash860 2013

[49] M Khan R A Qureshi M Hussain K Mehmood and R AKhan ldquoHexane soluble extract ofMallotus philippinensis (Lam)Muell Arg root possesses anti-leukaemic activityrdquo ChemistryCentral Journal vol 7 no 1 article 157 2013

[50] R Roshan S G Kulkarni S P Tupe et al ldquoAntifungal dimericchalcone derivative kamalachalcone E from Mallotus philip-pinensisrdquo Natural Product Research Formerly Natural ProductLetters vol 28 no 4 pp 245ndash250 2014

[51] H Nakane M Arisawa A Fujita S Koshimura and KOno ldquoInhibition of HIV-reverse transcriptase activity by somephloroglucinol derivativesrdquo FEBS Letters vol 286 no 1-2 pp83ndash85 1991

[52] T Furumoto N Ozawa Y Inami et al ldquoMallotus philippinensisbark extracts promote preferential migration of mesenchymalstem cells and improve wound healing in micerdquo Phytomedicinevol 21 no 3 pp 247ndash253 2014

[53] Maeda ldquoMethod for producing Mallotus philippinensis dyecomposition and the compositionrdquo US7556829 B2 2009

[54] C Wiart Medicinal Plants of the Asia-Pacific Drugs for theFutureWorld Scientific Singapore 2006

[55] V R Sharma ldquoA review on endangered plant of Mallotusphilippinensis (Lam) MArgrdquo Pharmacologyonline vol 3 pp1256ndash1265 2011

[56] V Tangpu T Temjenmongla and A K Yadav ldquoAnticestodalproperty of Strobilanthes discolor an experimental study inHymenolepis diminutamdashratmodelrdquo Journal of Ethnopharmacol-ogy vol 105 no 3 pp 459ndash463 2006

[57] V Tangpu K Temjenmongla and A K Yadav ldquoAnticestodalactivity ofTrifolium repens extractrdquo Pharmaceutical Biology vol42 no 8 pp 656ndash658 2004

[58] A K Yadav and T Temjenmongla ldquoAnticestodal activity ofHouttuynia cordata leaf extract againstHymenolepis diminuta inexperimentally infected ratsrdquo Journal of Parasitic Diseases vol35 no 2 pp 190ndash194 2011

[59] T Temjenmongla and A K Yadav ldquoAnticestodal efficacy ofLasia spinosa extract against experimental Hymenolepis dimin-uta infections in ratsrdquo Pharmaceutical Biology vol 44 no 7 pp499ndash502 2006

BioMed Research International 13

[60] M L Dhar M M Dhar B N Dhawan B N Mehrotra and CRay ldquoScreening of Indian plants for biological activityrdquo IndianJournal of Experimental Biology vol 6 no 4 pp 232ndash247 1968

[61] Temjenmongla and A K Yadav ldquoAnticestodal efficacy offolklore medicinal plants of Naga tribes in north-east IndiardquoAfrican Journal of Traditional Complementary and AlternativeMedicines vol 2 pp 129ndash133 2005

[62] T V Tangpu and A K Yadav ldquoAnticestodal efficacy of Psidiumguajava against experimental Hymenolepis diminuta infectionin ratsrdquo Indian Journal of Pharmacology vol 38 no 1 pp 29ndash32 2006

[63] R Singh A Mehta P Mehta and K Shukla ldquoAnthelminticactivity of Rhizome extracts of Curcuma longa and Zingiberofficinalerdquo International Journal of Pharmacy and Pharmaceu-tical Sciences vol 3 no 2 pp 236ndash237 2011

[64] M K Asha D Prashanth B Murali R Padmaja and A AmitldquoAnthelmintic activity of essential oil of Ocimum sanctum andeugenolrdquo Fitoterapia vol 72 no 6 pp 669ndash670 2001

[65] J B Githiori J Hoglund P J Waller and R L Baker ldquoTheanthelmintic efficacy of the plantAlbizia anthelmintica againstthe nematode parasites Haemonchus contortus of sheep andHeligmosomoides polygyrus of micerdquo Veterinary Parasitologyvol 116 no 1 pp 23ndash34 2003

[66] N M Enwerema J I Okoguna C O Wambebea D A Oko-rieb and P A Akahc ldquoAnthelmintic activity of the stem barkextracts of Berlina grandiflora and one of its active principlesBetulinic acidrdquo Phytomedicine vol 8 pp 112ndash114 2001

[67] Z Iqbal M Lateef A Jabber M N Ghayur and A HGilani ldquoIn vitro and in vivo anthelmintic activity of Nicotianatabacum L leaves against gastrointestinal nematodes of sheeprdquoPhytotherapy Research vol 20 no 1 pp 46ndash48 2006

[68] Z Iqbal M Lateef A Jabbar G Muhammad and M N KhanldquoAnthelmintic activity of Calotropis procera (Ait) Ait F flowersin sheeprdquo Journal of Ethnopharmacology vol 102 no 2 pp 256ndash261 2005

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MEDIATORSINFLAMMATION

of

Page 2: Mallotus philippinensis Muell. Arg (Euphorbiaceae ...

2 BioMed Research International

Table 1 Some medicinal plants reported for the antihelmintic activity

S no Sources Part used Family Reference1 Strobilanthes discolor Leaves Acanthaceae [56]2 Trifolium repens Aerial shoot Fabaceae [57]3 Houttuynia cordataThumb Leaves Piperaceae [58]4 Lasia spinosa Linn Leaves stalk stem Araceae [59]5 Centella asiatica Linn Leaves Apiaceae [60]6 Clerodendrum colebrookianumWalp Leaves Verbenaceae [61]7 Gynura angulosa DC Leaves Asteraceae [61]8 Aloe vera Linn Leaves Liliaceae [61]9 Psidium guajava Linn Leaves Myrtaceae [62]10 Curcuma longa Linn Rhizomes Zingiberaceae [63]11 Ocimum sanctum Linn Oileugenol Lamiaceae [64]12 Albizia anthelmintica Steam bark Mimosaceae [65]13 Berlinia grandiflora Steam bark Leguminosae [66]14 Nicotiana tabacum L leaves Solanaceae [67]15 Calotropis procera (Ait) Ait Flowers Asclepiadaceae [68]

class Magnoliopsidasubclass Rosidaeorder Euphorbialesfamily EuphorbiaceaegenusMallotusspeciesMallotus philippinensis

12 Botanic Description Trees are small to medium-sizedmonoecious in nature up to 25m tall and with a bole upto 50 cm in diameter but usually much less in number(Figure 19(a)) Slash turning deep red Branchlets are reddish-brown glandular

Leaves are alternate and simple more or less leatheryovate to lanceolate cuneate to rounded with two glands atbase Leaves are mostly acute or acuminate at apex conspicu-ously 3-nerved hairy and reddish glandular beneath petiolesize 1ndash4 cm long puberulous and reddish-brown in color(Figure 19(b))Male flowers in terminal and axillary position2ndash10 cm long solitary or fascicled paniculates spikes eachflowers are with numerous stamens small female flowershave spikes or slender racemes each flower with a stellatehairy 3 celled ovary with 3 papillose stigmas Fruit is adepressed-globose 3-lobed capsule 5 7mm and 10mm stel-late puberulous with abundant orange or reddish glandulargranules 3-seeded (Figure 19(d)) Seeds are subglobose andblack in color and 4mm across (Figure 19(e)) [5]

13 Biology In this genusMallotus philippinensis (M philip-pinensis) flowers mature from March to April and fruitsmature in July-August M philippinensis has extra floralnectaries attracting ants

14 Ecology M philippinensis has a widespread natural dis-tribution from the western Himalayas through India SriLanka to southern China and throughout Malesia to Aus-tralia Sometimes it is gregarious butmore usuallymixedwith

other species both in forests and open scrubland Kamalatree is common in evergreen forest especially in secondaryforest and sometimes even dominant in the undergrowthKamala tree withstands considerable shade it is frost-hardyand resistant to drought

15 Biophysical Limits Kamala tree is mostly grown at analtitude of 0ndash1600mat amean annual temperature of 16ndash28∘Cwith mean annual rainfall of 800ndash2000mm Plants will growmostly in a wide range of soil types including infertile soilslimestone acid and rocky land

2 Vernacular Names and Traditional Uses

21 Vernacular Names The vernacular names are as fol-lows English Kamala tree Hindi Kamala Sindur Rohiniand Kambhal Bengali Kamala Kamalagundi GuajaratiKapilo Kannad Kampillaka Kunkumadamara MalayalamSinduri Manjana Kuramatakku Kampipala and PonnagamMarathi Shindur Shendri and Kapila Punjabi KumilaKamal Kambal and Kamela Tamil Kapli KungumamKurangumanjanatti Kamala Manjanai Kunkumam andKamala Telugu Kunkuma Chendra-sinduri Kapila Vassun-tagunda Sundari Vasanta and Kumkumamu ArabicKinbilAssam Gangai Puddum and Lochan Oriya Bosonto-gundiKumala Sundragundi and Kamalagundi Pers Kanbela San-thal Rora

22 Traditional Uses According to Ayurveda leaves arebitter cooling and appetizer All parts of plant like glandsand hairs from the capsules or fruits are used as heat-ing purgative anthelmintic vulnerary detergent maturantcarminative and alexiteric and are useful in treatment ofbronchitis abdominal diseases and spleen enlargement andif taken with milk or curd (yoghurt) it can be quite useful forexpelling tapeworms [6] Kamala or Kampillakah is also usedas an oral contraceptive The powder and a few other parts of

BioMed Research International 3

Table 2 Cardenolide and its derivatives

O

O

O

Me

OH

H

H

HR1

R2

No Name R1 R2 References1 Coroglaucigenin CH2OH H [8]2 Coroglaucigenin L-rhamnoside CH2OH L-rham [8]3 Corotoxigenin CHO H [8]4 Corotoxigenin L-rhamnoside CHO L-rham [8]

Kamala are also used in external applications to promote thehealing of ulcers and woundsThey are used to treat parasiticaffections of the skin like scabies ringworm and herpes

23 Common Adulterants Glandular hair powder of Mphilippinensis is commonly adulterated with Annato dye(Bixa orellana Linn) ferric oxide brick dust and ferruginoussand Casearia tomentosa (stem bark powder) Carthamustinctorius (flower powder) Ficus benghalensis (fruit powder)and Flemingia macrophylla (hairs of fruits) are also reportedto be used as adulterant or substitute of Kampillaka [7]

3 Chemical Constituents

Major phytochemicals present in this genus contain dif-ferent natural compounds mainly phenols diterpenoidssteroids flavonoids cardenolides triterpenoids coumarinisocoumarins and many more to discover Present knowl-edge about this endangered species of medicinal plant isstill limited with respect to its phytochemistry and biologicalactivity However some researchers have contributed towardsisolation of some novel constituents and their activity One ofthe major chemical constituent that is rottlerin ofM philip-pinensis is listed below with its chemical structure and itsmajor biological activities along with other phytochemicals(Figure 18)

31 Cardenolides M philippinensis seeds contain cardeno-lides The seeds of M philippinensis were found to containafter fermentation four cardenolides (Table 2) of whichtwo were newly reported corotoxigenin L-rhamnoside andcorogl-aucigenin L-rhamnoside [8]

32 Triterpenoids Some Mallotus species were found tohave a characteristic feature of pentacyclic triterpenoids witha 66665 ring system The petroleum ether extract of

Table 3 Lupeol and its derivatives

H

H

H

H

CH3

CH3

CH3CH3

CH3

CH2

OR

H3C

H3C

No Name R1 References6 Lupeol-3-acetate Ac [9]7 Lupeol H [9]

AcO

OHH

H

H

HCH3

CH3

CH3CH3

CH2

H3C

H3C

Figure 1 Betulin-3-acetate

HHH

O

CH3

CH3

CH3

CH3

CH3

CH3

CH3

H3C

Figure 2 Friedelin

the heartwood of M philippinensis yielded triterpenoidsbetulin-3-acetate (Figure 1) as a major compound lupeolacetate (Table 3) and lupeol (Table 3) [9] Friedelane-typetriterpenoids are very common inMallotus species Friedelin(Figure 2) was obtained from the stem bark of M philip-pinensis [10] Most of the genera of family Euphorbiaceaesuch as Drypetes [11] or Celaenodendron [12] also containfriedelin in rich amount Friedelin is common and is alsofound in plants from other orders Other known pentacyclicterpenoids that is acetylaleuritolic acid (Figure 3) found tobe reported in the petroleum and ether extracts from barkof M philippinensis [9] The first olean-18-ene triterpeneoxidized at C-22 (Figure 4) was isolated from the stem bark

4 BioMed Research International

AcOH

H

H

CH3

CO2H

H3C

H3C

CH3 CH3

CH3

CH3

Figure 3 Acetylaleuritolic acid or aleuritic acid acetate

H

H

H

O

O

OH

CH3

CH3

CH3 CH3

CH3

CH3

H3C

H3C

H3C

Figure 4 3b-Acetoxy-22b-hydroxyolean-18-ene

of M Philippinensis [10] Apart from above triterpeniodsursane-type triterpenoid a-amyrin (Figure 5) reported fromthe petroleum ether and ethereal extracts ofM philippinensisbark [9]

33 Steroids Common steroid b-sitosterol (Figure 6) wasisolated from petroleum ether extracts of the heartwood andbark ofM philippinensis [9] Daucosterol was obtained fromether extract from bark ofM philippinensis [9]

34 Phenolic Compounds Isocoumarins Bergenin(Figure 7) an isocoumarin was isolated in 1972 fromthe heartwood ofM philippinensis This compound was alsoobtained from the bark and the leaves of M philippinensis[9]

Two new chalcone derivatives (flavonoids) kamalachal-cones A and B (Figures 8-9) with a unique ring systemcaused by dimerization between a dimethylchromene ringand a phenoxyl group were isolated from kamala (Mphilippinensis) [13] Three other novel chalcone derivativesmallotophilippens C D and E (Figures 10 11 12 13 and 14)were isolated from the fruits ofM philippinensis [14] lignanschalcones and dimeric chalcone derivatives [15]

Four phloroglucinol derivatives (kamalins) rottlerin andisorallorottlerin (Figures 15 and 16) were isolated from Mphilippinensis [16] Isorottlerin (Figure 17) was also men-tioned inM philippinensis [17]

Fruit and bark of plant contain condensed tanninsresponsible for antioxidant activity Methanolic bark extract

H

H

H

HO

CH3

CH3

CH3

CH3

CH3CH3

H3C

H3C

Figure 5 120572-Amyrin

H

H

H

H

OR

CH3

CH3

H3Ci-Pr

Et

Figure 6 120573-Sitosterol

OH

OHOH

OH

HO

MeO

O

O

O

Figure 7 Bergenin

O

O

O

O O

CH3

CH3

CH3

CH3

H3C

H3C

H

H

HHO

HO OH

Figure 8 Kamalachalcone A

BioMed Research International 5

O

O

O

O

O O

CH2

CH3

CH3

CH3

CH3

H3C

H3C

H3C

H

H

H

HO

HO

HO

HO OH

OH

Figure 9 Kamalachalcone B

O O

OOH

OHOH

HO HO 2

3

45

6

78

9

10

1112

1314

15

1998400

2998400

3998400

4998400

5998400

6998400

7998400

8998400

Figure 10 Mallotophilippen A or 1-[57-dihydroxy-22-dimethyl-6-(246-trihydroxy-3-isobutyryl-5-methyl-benzyl)-2H-chromen-8-yl]-2-methyl-butan-1-one

of M philippinensis subjected to characterization throughcolumn chromatography on a Sephadex LH-20 column usingethanol and acetone-water as the mobile phases tanninsand phenols were quantified Bark extract contains 541mggof total phenolics and infractions ranging from 54mgg(fraction I) to 927mgg (fraction VI) and condensed tanninswere detected in fractions IIndashVI [18 19] In 1989 leaves ofM philippinensis were reported for tannins and other relatedcompounds by Saijo et al [20]

35 Other Compounds Unsaturated fatty acids that is triply-unsatured hydroxy acid kamlolenic acid different fatty acidsand glyceride [21] have been reported from Kamala (Mphilippinensis) seed oil

Resinous coloured material contains active parts of rott-lerin and isorottlerin It also contains homorottlerine red role50 yellow role 5 manure 2 volatile oils tannin gumcitric acid and oxalic acid

4 Pharmacological Activities

41 Antifilarial Activity The effect of aqueous and alcoholicleave extracts of M philippinensis (Lam) Muell was studiedon the spontaneous movements of the whole worm and

O O

OOH

OHOH

HO HO 2

3

45

6

78

9

10

1112

1314

15

1998400

2998400

3998400

4998400

5998400

6998400

7998400

Figure 11 Mallotophilippen B or 1-[6-(3-acetyl-246-trihydroxy-5-methyl-benzyl)-57-dihydroxy-22-dimethyl-2H-chromen-8-yl]-2-methyl-butan-1-one

OH

OH

HO

OHO

Figure 12 Mallotophilippen C or (1-[6-(37-dimethyl-octa-26-dienyl)-57-dihydroxy-22-dimoethyl-2H-chromen-8-yl]-3-(4-hy-droxy-phenyl)-propenone) R = H

OH

OH

OHO

OHO

Figure 13 Mallotophilippen D or 3-(34-dihydroxy-phenyl)-1-[6-(37-dimethyl-octa-26-dienyl)-57-dihydroxy-22-dimethyl-2H-chromen-8-yl]-propenone R = OH

nerve-muscle (nm) preparation of Setaria cervi and on thesurvival of microfilariae in vitro Both the extracts result ininhibition of spontaneous motility of whole worm and thenm preparation of S cervi characterized by initial stimula-tion followed by depression in amplitude The tone and rateof contractions remained visibly unaffected Aqueous extractat higher concentration showed immediate reduction in toneThe concentration required to inhibit the movements of nmpreparation was 15th for aqueous and 111th for alcoholicextract compared to that for the whole worm suggesting acuticular permeability barrier The stimulatory response ofacetylcholine was blocked by aqueous extract onwhole worm

6 BioMed Research International

OH

OH

OH

O

OHO

Figure 14 Mallotophilippen E or 1-[57-dihydroxy-2-methyl-6-(3-methyl-but-2-enyl)-2-(4-methyl-pent-3-enyl)-2H-chromen-8-yl]-3-(34-dihydroxy-phenyl)-propenone

OH

OH

OHOH

O

O

O

HO

Figure 15 Rottlerin

movements On the microfilariae the LC50and LC

90were 18

and 20 ngmL for aqueous and 12 and 15 ngmL for alcoholicextracts respectively [2] Further study will be required toevaluate the same activity with its phytochemicals

42 Antifertility Activity Seeds extract of M philippinensisexhibits adverse effects on different reproductive parametersof female rats According to the study extract reducesserum FSH and LH levels probably by affecting hypotha-lamicpituitary axis in experimental animals This reducedlevel may affect follicular development quality of ovulatedeggs corpus luteum formation estrus cycle andmaintenanceof pregnancy in rats [22] This antifertility effect of plantextract is supposed to be caused by rottlerin (Figure 15) aphloroglucinol derivative Acetyl rottlerin may be active butisorottlerin (Figure 17) is either inactive or slightly active [23]Effect of pure rottlerin can be further studied so as to clarifythe potential of phloroglucinol derivatives

43 Antibacterial and Antifungal Activity A series of 61Indian medicinal plants belonging to 33 different familiesused in various infectious disorders were screened for theirantimicrobial properties Screening was carried out at 1000and 500 120583gmL concentrations by agar dilution methodagainst Bacillus cereus varmycoides Bacillus pumilus Bacillussubtilis Bordetella bronchisepticaMicrococcus Luteus Staphy-lococcus aureus Staphylococcus epidermidis Escherichia coli

OH

OH

O

O

O

HO

HO

HO

Figure 16 Isoallorottlerin

OH

OH

O

O

O

OHO

HO

Figure 17 Isorottlerin

Klebsiella pneumonia Candida albicans and Saccharomycescerevisiae Twenty-eight plant extracts showed activity againstat least one of the test organisms used in the screeningOn the basis of the results obtained study concludes thatthe crude extracts of M philippinensis exhibited significantantimicrobial activity [3] and properties that support folk-loric use in the treatment of some diseases as broad-spectrumantimicrobial agents Steam bark of plant and its chloroformfractions and the methanolic extract significantly inhibitthe pathogenic bacteria with significant zones of inhibitioncomparable to the standard drug used However the hexanicextract did not show any significant activity [24] Glandularhair of fruits of Mallotus exhibits significant antibacterialactivity against human pathogenic bacteria withMIC ranging15ndash20mgmL This extract does not show any inhibitionagainst different species of candida This shows that fruitextract possesses antibacterial activity without any antifungalpotential The results of the study may justify the use of theplant against bacterial pathogens This probably explains theuse of these plants by the indigenous people against a numberof infections [25]

However ethanolic extract shows potent anti-Heli-cobacter pylori activity at the concentration of 156ndash312mgLagainst eight H pylori strains Further purification of extractrevealed that rottlerin exhibits potent bactericidal effectwith minimal bactericidal concentration (MBC) of 312ndash625mgL against different resistant strains of clarithromycin

BioMed Research International 7

M philippinensis

Rottlerin

Fruit

H3C

HO

HO

OH OH

OH

O

O

O

CH3

CH3

CH3

Antifertility

Antimicrobial

Protein inhibition

Antituberculosis activity

Antiallergic activity

Antiproliferative activity

Antiparasitic (cestodal)

Figure 18 Rottlerin and its major biological activities

and metronidazole including Japanese and Pakistani strains[17]

44 Anti-Inflammatory and Immunoregulatory ActivityChalcones derivatives from the fruits of M philippinensisand mallotophilippens C D and E (Figures 12 13 and14) inhibit nitric oxide (NO) production and inducibleNO synthase (iNOS) gene expression by a murinemacrophage-like cell line (RAW 2647) which was activatedby lipopolysaccharide (LPS) and recombinant mouseinterferon-gamma (IFN-gamma) Further investigationssuggest the downregulation of cyclooxygenase-2 geneinterleukin-6 gene and interleukin-1b gene expressionThe above results show that these chalcones have goodanti-inflammatory and immunoregulatory effects [26]

45 Antioxidant Activity and Antiradical Activity Differentfractions of bark and fruit of Mallotus were studied forits total antioxidant activity (TAA) and antiradical activityagainst DPPH on a Sephadex LH-20 column using ethanoland acetone-water asmobile phase Among different extractsbark fraction showed the strongest antiradical activity (TAAvaluemdash527 mmol Trolox equivg) and reducing powerAnother extract that is phenolic fraction shows TAAranging from 058mmol Troloxg (fraction I) to 682mmolTroloxg (fraction IV) this is the strongest fraction showingantiradical activity against DPPH and reducing power TAAof other extracts ranged from 005 to 179mmol Troloxequivg [18 19]

46 Protein Inhibition Implicated in Cancer Processes Proteinkinase is inhibited with some specificity for PKC by rottlerina compound isolated from Mallotus Inhibition of PKCappears due to a strong competition between rottlerin andATP CaM-kinase III is suppressed by rottlerin as effectivelyas PKC 120575 among different protein kinases tested Novelinhibition property and improved selectivity for a distinctPKC isoenzyme of rottlerin are suggestive from its chemicalstructure [27 28] Rottlerin is also very potent in blockingother kinases including AktPKB and p38 MAPK [29ndash31] Italso inhibits human T cell responses [32] reduces MUC5ACexpression in human epithelial cells [33] abrogates reactiveoxygen species production in hepatic stellate cells [34] andprevents histamine-induced H1-receptor gene expression inHeLa cells [35] However still very limited information isavailable of rottlerin towards cancer disease and its mecha-nism of action

47 Hepatoprotective Activity Methanolic extract of Mphilippinensis leaves decreases the CCl

4-induced elevation in

biochemical parameters (SGOT SGPT SALP direct biliru-bin total bilirubin andMDA) on pretreatment at doses 100ndash200mgkg and also reversed the functional and antioxidantparameters This study suggests that leave extract was effec-tive in functional improvement of hepatocytes Histopatho-logical studies also suggest the hepatoprotective activity ofplant [36]

48 In Vitro Cytotoxicity against Human Cancel Cell Glan-dular hair extract of Mallotus fruit powder was assayed

8 BioMed Research International

(a) (b)

(c) (d)

(e)

Figure 19 Mallotus philippinensis (a) Mature plant (b) leaf (c) initial inflorescence of seed setting (d) mature fruits twig (e) mature fruitwith seed

against 14 human cancer cell lines among different fractions95 ethanolic extract showed the highest cytotoxic effect ascompared to 50 ethanolic and aqueous portion Furtherthe chromatographic analysis of the said fraction afforded apolyphenolic molecule rottlerin inMallotus plant [37]

49 Anticestodal ActivityVeterinary Applications M philip-pinensis fruit was found to be very effective against gas-trointestinal cestodes in Beetal goats and other ruminantsComparative anticestodal efficacies of single oral dose treat-ments with the powdered fruit ofM philippinensis (125 250and 375mgkg) its water or methanol extracts (equivalent to375mgkg) and the total glycosides (25 50 and 100mgkg)were determined in naturally cestode-infected Beetal goats[38] An ethnobotanical survey has been conducted foranthelmintics in ruminants so as to document the plantsused to treat and control helminthes Mallotus has beenfrequently used to treat helminthosis in ruminants [39] M

philippinensis fruit extract of 800mgkg twice daily for 3days was observed to have curative efficacy against matureadult worms of Hymenolepis diminuta The total follow-upperiod of 90 days did not show any further excretion of eggsin the faeces of treated rats Praziquantel at the dosage of5mgkg also produced a similar effect [40] In vitro scolicidalactivity ofM philippinensis (Lam)Muell Arg fruit glandularhair extract against hydatid cyst Echinococcus granulosusprotoscoleces at concentrations 10 and 20mgmL shows themortality rate 97 to 99 respectively for 60min treatmentwhile up to 93 mortality was observed with 20mgmLfor only 10min treatment This proves that the extract hassignificant scolicidal activity with almost no associated sideeffects [41] In vivo animal model experiment will be furtherrequired to prove its effect against Hydatid cyst

410 Purgative Activity and Anthelmintic Activity A signifi-cant purgative effect after an oral dose (120mgkg) in rats was

BioMed Research International 9

assessed from resins isolated from plant Its effect was evalu-ated from the weight of faeces as well as from surface areaof blotting paper soaked by liquid faeces The anthelminticeffect on tape worm was evaluated in albino rates fromthe resin of the plant showed lethal effect of 3569 and7821 respectively in small intestine in concentrations 60and 120mgkg respectively [42 43]

411 Antituberculosis Activity Organic extract of plant afterbioassay-directed fractionation yields five compounds themost active of which againstMycobacterium tuberculosis wasa new compound 8-cinnamoyl-57-dihydroxy-22-dimethyl-6-geranylchromene for which the name mallotophilippenF is suggested The second compound 8-cinnamoyl-22-dimethyl-7-hydroxy-5-methoxychromene was isolated froma natural source for the first time while the remaining threecompounds rottlerin isoallorottlerin or isorottlerin andthe so-called ldquored compoundrdquo 8-cinnamoyl-57-dihydroxy-226-trimethylchromene had been already isolated fromthis plant Isolated compounds were identified by 2D-NMRand C-13 NMR [44] Ethanolic extract of plant was assayedfor antimycobacterial activity against M smegmatis by discdiffusion assay Further antituberculosis potential of leavesextract was identified by radiometric BACTEC assay resultrevealed that ethanolic extract ofM philippensis showed anti-tuberculosis activity against virulent and avirulent strains ofM tuberculosis H37Rv andM tuberculosis H37Ra with min-imum inhibitory concentrations of 025 and 0125mgmLminus1respectively The inhibition in growth index values of Mtuberculosis was observed in the presence of ethyl acetatefraction at a minimum concentration of 005mgmLminus1 Itsuggests that ethanolic and ethyl acetate fraction of plantpossesses significant antimycobacterial activity [45] Steambark of M philippinensis has also been reported for itsantitumor promoting effect which was due to the presenceof 3120572-Hydroxy-DA-friedooleanan-2-one [46]

412 Antiallergic Activity M philippinensis fruit containstwo new phloroglucinol derivatives mallotophilippensA and B (Figures 10 and 11) which were identified usingchemical and spectral data as 1-[57-dihydroxy-22-di-methyl-6-(246-trihydroxy-3-isobutyryl-5-methyl-benzyl)-2H-chromen-8-yl]-2-methyl-butan-1-one and 1-[6-(3-Acetyl-246-trihydroxy-5-methyl-benzyl)-57-dihydroxy-22-dim-ethyl-2H-chromen-8-yl]-2-methyl-butan-1-one respe-ctively These compounds inhibited the production ofnitric oxide (NO) and inducible NO synthase (iNOS) geneexpression by a murine macrophage-like cell line (RAW2647) which was activated by lipopolysaccharide (LPS)and recombinant mouse interferon-g (IFN-g) Furtherphloroglucinol derivatives inhibit histamine release from ratperitoneal mast cells induced by compound 4880This studysuggests its anti-inflammatory activity [47] Rottlerin hasbeen tested in animal models of IgE-dependent anaphylaxisand the antiallergic mechanisms of action in mast cellsAntiallergic action of rottlerin has been tested in passivecutaneous anaphylaxis and passive systemic anaphylaxismouse models and in anaphylactic contraction of bronchial

rings isolated from sensitized guinea pigs This experimentsproves antiallergic effect of rottlerin by blocking IgE-inducedmast cell degranulation This report suggests the use ofrottlerin in mast cell-mediated allergic disorders includingurticaria and allergic asthma [48]

413 Anti-Leukaemic Activity Root extract ofM philippinen-sis was tested on human promyelocytic leukemia HL-60 cellproliferation cell cycle regulators and apoptosis in order toinvestigate its antileukemic effect Hexane fraction showedpromising toxicity against p53-deficient HL-60 cells (IC

50

15mg dry roots equivalentmL medium) after 72 h andinterestingly inhibition of cell proliferation was preceded bythe upregulation of the protooncogenes Cdc25A and cyclinD1 within 24 hours suggesting its antileukemic effect inHL-60 cells After isolation and identification by GC-MSpolyphenols were the main compounds of the hexane extractthat inhibited proliferation and induced apoptosis [49]

414 Antiproliferative Activity Antiproliferative effect wasevaluated against Thp-1 cell lines from the isolated com-pounds of M philippinensis fruit extract in which 41015840-hydroxyrottlerin showed 54 growth inhibition ofThp-1 cellline [50] Other isolated compounds were also tested againstdifferent fungi andwere found to be very effective IC

50values

415 Anti-HIV Activity Four phloroglucinol derivativesnamed mallotophenone (5-methylene-bis-26-dihydroxy-3-methyl-4-methoxyacetophenone) mallotochromene (8-acetyl-57-dihydroxy-6-(3-acetyl-24-dihydroxy-5-methyl-6-methoxybenzyl)-22-dimethylchromene) mallotojaponin(3-(33(dimethylallyl) S-(3(acetyl-24-dihydroxy-5-methyl-6-methoxybenzyl)-phloracetophenone) andmallotolerin (3-(3-methyl-2-hydroxybut-3-enyl)-5-(3-acetyl-24-dihydroxy-5-methyl-6-methoxybenzyl)-phloracetophenone) weretested for their ability to inhibit the activity of humanimmunodeficiency virus- (HIV-) reverse transcriptaseThe mode of inhibition of mallotojaponin was foundto be competitive with respect to the template primer(rA)n (dT)12ndash18 and noncompetitive with respect to thetriphosphate substrate dTTPThe Ki value of mallotojaponinfor HIV-reverse transcriptase was determined to be 61 120583M[51]

416 Antitumor Activity Four known friedelane-type trit-erpenoids friedelin 3-hydroxy-DA-friedoolean-3-en-2-one 2120573-hydroxy-DA-friedooleanan-3-one and 3120572-hy-droxy-DA-friedooleanan-2-one and two known lupane-type triterpenoids lupeol and betulin were isolated fromthe stem bark of M philippinensis and were tested fortheir inhibitory effects on Epstein-Barr virus early antigen(EBV-EA) activation induced by 12-O-tetradecanoylphorbol13-acetate (TPA) The inhibitory effect of compounds 2(IC50

= 292mol ratio32 pmolTPA) and 4 (IC50

= 288) wasstronger than those of the other compounds tested and thepositive control curcumin (IC

50= 343) Compound 3120572-

hydroxy-DA-friedooleanan-2-one strongly inhibited mouse

10 BioMed Research International

skin tumor promotion in an in vivo two-stage carcinogenesismodel [46]

417 Wound Healing and Mesenchymal Stem Cell (MSC)Proliferation Bark extract ofMallotus philippinensis has beentested in vitro for wound healing activity by examining theproliferation and migration of MSCs KUM6 cells prolifer-ation and migration have been enhanced at 016ndash4 120583gmLand unregulated the activity of MSCs by secreting variouscytokines to wounded site from bone marrow to systemiccirculation and finally remodel wounded tissues [52]

418 Toxicities Seeds of M philippinensis ethereal extracthave adverse effect on various parameters of female rats Eventhe extract reduces serum levels of gonadotropins in treatedanimals at high dose of 100mgkg body weight Reducedweights of ovary and uterus follicular development andincreased atretic follicular in the ovary are due to subnormallevels of steroid hormones Thus pregnancy is very difficultin female rats treated with kamala seed extract [22]

419 Colouring Agent-Dye Glandular hairs of fruit aremostly used as an orange dye for silk [53 54]

5 Pharmacognostic Evaluation ofMallotus philippinensis

Morphological study shows that fruit depresses globoseand is three-lobed capsule 5ndash7mm times 8ndash10ndash12mm stellate-puberulose and with abundant orange or reddish glan-dular granules Seeds are subglobose and black in colorOrganoleptic property of the red fruit shows that it is tastelessand odourless Microscopic description showed the presenceof epicarp which contained a compactly packed layer ofmucilaginous cells and mesocarp composed of columnarcells which are closely arranged Its polygonal cells are com-pactly arranged in 2-3 layers Presence of lignified vasculararrangement has been observed in the transverse section [55]

6 Conclusion and Future Perspective

Medicinal plants have been clinically used and its interest hasbeen dramatically increased over the past decades throughoutthe world and its formulations are increasingly cited inmedia Daily consumption of the natural products and theirformulations by an extensive number of patients lead toserious concern for scientist to study its efficacy and safetyBecause of extensive use and its benefits natural productsin many countries are regulated both as medicinal productsand as food supplements often labeled as natural foodsupplements

Traditional use and its growing demand for Mallotusphilippinensis and its other species lead to compile this reviewand commented on the current knowledge provided byclinical and preclinical research on the effect of this plant

Mallotus philippinensis has been widely used as tradi-tional medicine in several parts of countries including IndiaEvery part of this plant possesses its specific medicinal prop-erties and is usedmainly in ayurveda to fight against intestinalworms in domestic and grazing animals when administeredwith jaggeryHowever only a few reports are attributed to thisplant and its different parts and there is a large scope for inves-tigation Hence it is required to explore more of its potentialwithin the field of medicinal and pharmaceutical sciences fornovel and fruitful application of this plant in form of naturalformulation Along with this medicinal importance thisplant is used against human pathogens including H pylorianti-inflammatory activity antioxidant antiradical proteininhibition hepatoprotective antiallergic anti-HIV activityand many more Phytochemical investigation revealed that alarge number phenol derivatives and several miscellaneouscompounds from different classes have been isolated fromthis species The phenols diterpenoids steroids flavonoidscardenolides triterpenoids coumarins and isocoumarinsare mostly distributed in all parts of the plant The othermajor isolated pure compounds from this species mostlybelong to phenolic group exhibiting most of the biologicalactivity Various types of extracts from different parts andsingle compounds derived from this species have beenfound to possess biological activities including antioxidantantimicrobial anti-inflammatory cytotoxicity and immunemodulatory Fruit and bark of plant contain condensed tan-nins responsible for antioxidant activity Somenovel chalconederivatives mallotophilippens C D and E were isolatedfrom the fruits of M philippinensis Mallotoxin or rottlerinhas great anticancerous potential Among the ever-anticanceragents rottlerin appears to have great potentiality for beingused in chemotherapy Rottlerin will become a potentialmolecule for research in future to treat cancerous cell as itwill affect cell machineries involved in apoptosis survivaland autophage This suggests the view that this species haspotential to be a beneficial chemotherapeutic remedy

Although the data and other reports provided that thismedicinal plant is of great biological use in different phar-macological activities including anticancer further researchis needed in different areas regarding the toxicity and efficacyof pure phytochemicals isolated from different parts of thisplant More data will be needed from preclinical and clinicalstudies on humans to clarify its potency and safety aslack of knowledge with respect to its adverse effects andmethodological accuracy in the literature limits towardsits standardized formulation Furthermore the mechanismof action of the phytochemicals and extract of Mallotusphilippinensis is unclear more exhaustive studies will beperformed to explore its mechanism and structure activityrelationship among various constituents

In conclusion this review confirms the great potential ofMallotus philippinensis As very limited information is stillknown for this species it leads us to continue the study ondifferent species of Mallotus plant and its interesting phar-macological properties Further natural product chemistryof isolated moiety and its structural analysis of compounds

BioMed Research International 11

responsible for these activities will be an interesting field ofresearch

Conflict of Interests

The authors declare that there is no conflict of interests re-garding the publication of this paper

Acknowledgment

The authors gratefully acknowledge the financial supportprovided by CSIR Government of India New Delhi forawarding SRF in the form of research fellowship

References

[1] C-J Widen and H S Puri ldquoNatural occurrence and chemicalvariability of phloroglucinols inKamalardquoPlantaMedica vol 40no 3 pp 284ndash287 1980

[2] R Singh K C Singhal and N U Khan ldquoAntifilarial activity ofMallotus philippinensisLam on Setaria cervie (Nematoda Filar-ioidea) in-vitrordquo Indian Journal of Physiology andPharmacologyvol 41 no 4 pp 397ndash403 1997

[3] V P Kumar N S Chauhan H Padh and M Rajani ldquoSearchfor antibacterial and antifungal agents from selected Indianmedicinal plantsrdquo Journal of Ethnopharmacology vol 107 no2 pp 182ndash188 2006

[4] S Shrikumar and T K Ravi ldquoApproaches towards developmentand promotion of herbal drugsrdquo Pharmaceutical Reviews vol 1no 1 pp 180ndash183 2007

[5] C Orwa A Mutua and R Kindt ldquoAgroforestree Database atree reference and selection guiderdquo Version 4 0 2009

[6] K Usmanghani A Saeed and M T Alam ldquoIndusynicMedicine Karachirdquo Research Institute of Indusyunic Medicinevol 1997 pp 285ndash287 1997

[7] F Ahmad and S Hashmi ldquoAdulteration in commercial Kamila(Mallotus philippinensisMuell) an anthelmintic drug of reputerdquoHamdard Medicus vol 38 pp 62ndash67 1995

[8] K D Roberts E Weiss and T Reichstein ldquoGlycosides andaglycons CCLII Cardenolides of the seed of Mallotus philip-pinensisrdquo Helvetica Chimica Acta vol 46 pp 2886ndash2893 1963

[9] M Bandopadhyay V K Dhingra and S K Mukerjee ldquoTriter-penoid and other components of Mallotus philippinensisrdquo Phy-tochemistry vol 11 no 4 p 1511 1972

[10] S P Nair and J Madhusudana Rao ldquoKamaladiol-3-acetate fromthe stem bark of Mallotus philippinensisrdquo Phytochemistry vol32 pp 407ndash409 1993

[11] J DWansi JWandjiW A Kamdem et al ldquoTriterpenoids fromDrypetes chevalieri Beille (Euphorbiaceae)rdquo Natural ProductResearch vol 20 no 6 pp 586ndash592 2006

[12] P Castenada A Bahena and E Garcia ldquoChemical studieson Mexican plants used in traditional medicine XXIX Sec-ondary metabolites from the stem bark of Celaeno-dendronmexicanumrdquo Journal of Natural Products vol 56 pp 1575ndash15791993

[13] T Tanaka T Ito M Iinuma Y Takahashi and H NaganawaldquoDimeric chalcone derivatives from Mallotus philippinensisrdquoPhytochemistry vol 48 no 8 pp 1423ndash1427 1998

[14] T M Nguyen V M Chau V K Phan et al ldquoStudy on chemicalconstituents of the leaves of Mallotus philippinensisrdquo Tap ChiHoa Hoc vol 48 pp 352ndash357 2010

[15] M Furusawa Y Ido T Tanaka et al ldquoNovel complex flavonoidsfrom Mallotus philippinensis (Kamala tree)rdquo Helvetica ChimicaActa vol 88 no 5 pp 1048ndash1058 2005

[16] M Lounasmaa C J Widen C M Tuuf and A HuhtikangasldquoOn the phloroglucinol derivatives of Mallotus philippinensisrdquoPlanta Medica vol 28 no 1 pp 16ndash31 1975

[17] S F H Zaidi I Yoshida F Butt et al ldquoPotent bactericidal con-stituents from Mallotus philippinensis against clarithromycinand metronidazole resistant strains of Japanese and Pakistanihelicobacter pylorirdquo Biological and Pharmaceutical Bulletin vol32 no 4 pp 631ndash636 2009

[18] M Arfan H Amin M Karamac et al ldquoAntioxidant activityof extracts of Mallotus philippinensis fruit and barkrdquo Journal ofFood Lipids vol 14 no 3 pp 280ndash297 2007

[19] M Arfan K Hazrat and K Magdalena ldquoAntioxidant activityof phenolic fractions of Mallotus philippinensis bark extractrdquoJournal of Food Science vol 27 no 2 pp 109ndash117 2009

[20] R Saijo G Nonaka and I Nishioka ldquoTannins and related com-pounds LXXXVIII Isolation and characterization of hydrolyz-able tannins fromMallotus japonicus (Thunb)Mueller-Arg andM philippinensis (Lam)Mueller-ArgrdquoChemical amp Pharmaceu-tical Bulletin vol 37 no 11 pp 2940ndash2947 1989

[21] S C Gupta S S Gupta and J S Aggarwal ldquoChemical exami-nation of the seeds of Mallotus philippinensis III Constitutionof kamlolenic acid isolated from the oilrdquo Journal of Scientific ampIndustrial Research vol 12 pp 240ndash242 1953

[22] S C Thakur S S Thakur S K Chaube and S P Singh ldquoAnetheral extract of Kamala (Mallotus philippinensis (Moll Arg)Lam) seed induce adverse effects on reproductive parametersof female ratsrdquo Reproductive Toxicology vol 20 no 1 pp 149ndash156 2005

[23] M L Gujral D R Varma K N Sareen and A K Roy ldquoOralcontraceptives II Antifertility effect ofMallotus philippinensisrdquoIndian Journal of Medical Research vol 48 pp 52ndash58 1960

[24] KMoorthy K Srinivasan C Subramanian CMohanasundariand M Palaniswamy ldquoPhyto-chemical screening and antibac-terial evaluation of stem bark of Mallotus philippinensis varTomentosusrdquoAfrican Journal of Biotechnology vol 6 no 13 pp1521ndash1523 2007

[25] M Gangwar D Kumar R Tilak et al ldquoQualitative phy-tochemical characterization and antibacterial evaluation ofglandular hairs ofMallotus philippinensis fruit extractrdquo Journalof Pharmacy Research vol 4 no 11 pp 4214ndash4216 2011

[26] A Daikonya S Katsuki and S Kitanaka ldquoAntiallergic agentsfrom naturalsources 9 Inhibition of nitric oxide productionby novel chalcone derivatives from Mallotus philippinensis(Euphorbiaceae)rdquo Chemical amp Pharmaceutical Bulletin vol 52no 11 pp 1326ndash1329 2004

[27] M Gschwendt H J Muller K Kielbassa et al ldquoRottlerina novel protein kinase inhibitorrdquo Biochemical and BiophysicalResearch Communications vol 199 no 1 pp 93ndash98 1994

[28] Y F Liao Y C Hung W H Chang et al ldquoThe PKC deltainhibitor rottlerin induces apoptosis of haematopoietic celllines through mitochondrial membrane depolarization andcaspasescascaderdquo Life Sciences vol 77 no 6 pp 707ndash719 2005

[29] H S Kang E K Park K H Kim et al ldquoReceptor activatorof nuclear factor-kappa B is induced by a rottlerin-sensitiveand p38 MAP kinase-dependent pathway during monocytedifferentiationrdquoMolecules and Cells vol 17 no 3 pp 438ndash4452004

12 BioMed Research International

[30] S P Soltoff ldquoRottlerin an inappropriate and ineffectiveinhibitor of PKC120575rdquo Trends in Pharmacological Sciences vol 28no 9 pp 453ndash458 2007

[31] Y Choi D K Kim S S Kang J K Sonn and E J Jin ldquoIntegrinsignaling and cell spreading alterations by rottlerin treatment ofchick limb bud mesenchymal cellsrdquo Biochimie vol 91 no 5 pp624ndash631 2009

[32] C Springael S Thomas S Rahmouni et al ldquoRottlerin inhibitshuman T cell responsesrdquo Biochemical Pharmacology vol 73 no4 pp 515ndash525 2007

[33] J H Choi Y P Hwang E H Han et al ldquoInhibition of acrolein-stimulated MUC5AC expression by Platycodon grandiflorumroot-derived saponin in A549 cellsrdquo Food and Chemical Toxi-cology vol 49 no 9 pp 2157ndash2166 2011

[34] E L M Guimaraes C Empsen A Geerts and L A vanGrunsven ldquoAdvanced glycation end products induce produc-tion of reactive oxygen species via the activation of NADPHoxidase in murine hepatic stellate cellsrdquo Journal of Hepatologyvol 52 no 3 pp 389ndash397 2010

[35] H Mizuguchi T Terao M Kitai et al ldquoInvolvement of pro-tein kinase C120575extracellular signal-regulated kinasepoly(ADP-ribose) polymerase-1 (PARP-1) signaling pathway in histamine-induced up-regulation of histamine H1 receptor gene expres-sion in HeLa cellsrdquo Journal of Biological Chemistry vol 286 no35 pp 30542ndash30551 2011

[36] S Ramakrishna K M Geetha P V V S Bhaskar gopalR P Kumar C P Madav and L Umachandar ldquoEffect ofMallotus PhilippinensisMuell-Arg leaves against hepatotoxicityof Carbon tetrachloride in ratsrdquo International Journal of Phar-maceutical Sciences and Research vol 2 pp 74ndash83 2011

[37] V Sharma ldquoA polyphenolic compound rottlerin demonstratessignificant in vitro cytotoxicity against human cancer celllines isolation and characterization from the fruits ofMallotusphilippinensisrdquo Journal of Plant Biochemistry and Biotechnologyvol 20 no 2 pp 190ndash195 2011

[38] M S Akhtar and I Ahmad ldquoComparative efficacy of Mallotusphilippinensis fruit (Kamala) or Nilzan drug against gastroin-testinal cestodes in Beetal goatsrdquo Small Ruminant Research vol8 no 1-2 pp 121ndash128 1992

[39] A Jabbar M A Raza Z Iqbal and M N Khan ldquoAn inventoryof the ethnobotanicals used as anthelmintics in the southernPunjab (Pakistan)rdquo Journal of Ethnopharmacology vol 108 no1 pp 152ndash154 2006

[40] M Gangwar A Dalai A Chaudhary et al ldquoStudy on activityof alcoholic extract of glands and hairs of fruits of Mallotusphilippinensis in murine cestodal infection modelrdquo Interna-tional Journal of Pharmacy amp Pharmaceutical Sciences vol 4no 1 pp 643ndash645 2012

[41] M Gangwar V C Verma T D Singh S K Singh R KGoel and G Nath ldquoIn-vitro scolicidal activity of Mallotusphilippinensis (Lam) Muell Arg fruit glandular hair extractagainst hydatid cyst Echinococcus granulosusrdquo Asian PacificJournal of Tropical Medicine vol 6 no 8 pp 595ndash601 2013

[42] S S Gupta P Verma and K Hishikar ldquoPurgative andanthelmintic effects of Mallotus philippinensis in rats againsttape wormrdquo Indian Journal of Physiology amp Pharmacology vol28 no 1 pp 63ndash66 1984

[43] A Hussain M N Khan Z Iqbal and M S Sajid ldquoAn accountof the botanical anthelmintics used in traditional veterinarypractices in Sahiwal district of Punjab Pakistanrdquo Journal ofEthnopharmacology vol 119 no 1 pp 185ndash190 2008

[44] Q Hong D E Minter S G Franzblau M Arfan H Amin andM G Reinecke ldquoAnti-tuberculosis compounds from Mallotusphilippinensisrdquo Natural Product Communications vol 5 no 2pp 211ndash217 2010

[45] V K Gupta C Shukla G R S Bisht D Saikia S Kumarand R L Thakur ldquoDetection of anti-tuberculosis activity insome folklore plants by radiometric BACTEC assayrdquo Letters inApplied Microbiology vol 52 no 1 pp 33ndash40 2011

[46] R Tanaka T Nakata C Yamaguchi S Wada T Yamadaand H Tokuda ldquoPotential anti-tumor-promoting activity of3120572-Hydroxy-D a-friedooleanan-2-one from the stem bark ofMallotus philippinensisrdquo Planta Medica vol 74 no 4 pp 413ndash416 2008

[47] A Daikonya S Katsuki J B Wu and S Kitanaka ldquoAnti-allergic agents from natural sources (4) anti-allergic activityof new phloroglucinol derivatives from Mallotus philippinensis(Euphorbiaceae)rdquo Chemical and Pharmaceutical Bulletin vol50 no 12 pp 1566ndash1569 2002

[48] T K Chan S W David C Cheng S P Guan H MKoh and W S Wong ldquoAnti-allergic actions of rottlerin fromMallotus philippinensisis in experimental mast cell-mediatedanaphylactic modelsrdquo Phytomedicine vol 20 no 10 pp 853ndash860 2013

[49] M Khan R A Qureshi M Hussain K Mehmood and R AKhan ldquoHexane soluble extract ofMallotus philippinensis (Lam)Muell Arg root possesses anti-leukaemic activityrdquo ChemistryCentral Journal vol 7 no 1 article 157 2013

[50] R Roshan S G Kulkarni S P Tupe et al ldquoAntifungal dimericchalcone derivative kamalachalcone E from Mallotus philip-pinensisrdquo Natural Product Research Formerly Natural ProductLetters vol 28 no 4 pp 245ndash250 2014

[51] H Nakane M Arisawa A Fujita S Koshimura and KOno ldquoInhibition of HIV-reverse transcriptase activity by somephloroglucinol derivativesrdquo FEBS Letters vol 286 no 1-2 pp83ndash85 1991

[52] T Furumoto N Ozawa Y Inami et al ldquoMallotus philippinensisbark extracts promote preferential migration of mesenchymalstem cells and improve wound healing in micerdquo Phytomedicinevol 21 no 3 pp 247ndash253 2014

[53] Maeda ldquoMethod for producing Mallotus philippinensis dyecomposition and the compositionrdquo US7556829 B2 2009

[54] C Wiart Medicinal Plants of the Asia-Pacific Drugs for theFutureWorld Scientific Singapore 2006

[55] V R Sharma ldquoA review on endangered plant of Mallotusphilippinensis (Lam) MArgrdquo Pharmacologyonline vol 3 pp1256ndash1265 2011

[56] V Tangpu T Temjenmongla and A K Yadav ldquoAnticestodalproperty of Strobilanthes discolor an experimental study inHymenolepis diminutamdashratmodelrdquo Journal of Ethnopharmacol-ogy vol 105 no 3 pp 459ndash463 2006

[57] V Tangpu K Temjenmongla and A K Yadav ldquoAnticestodalactivity ofTrifolium repens extractrdquo Pharmaceutical Biology vol42 no 8 pp 656ndash658 2004

[58] A K Yadav and T Temjenmongla ldquoAnticestodal activity ofHouttuynia cordata leaf extract againstHymenolepis diminuta inexperimentally infected ratsrdquo Journal of Parasitic Diseases vol35 no 2 pp 190ndash194 2011

[59] T Temjenmongla and A K Yadav ldquoAnticestodal efficacy ofLasia spinosa extract against experimental Hymenolepis dimin-uta infections in ratsrdquo Pharmaceutical Biology vol 44 no 7 pp499ndash502 2006

BioMed Research International 13

[60] M L Dhar M M Dhar B N Dhawan B N Mehrotra and CRay ldquoScreening of Indian plants for biological activityrdquo IndianJournal of Experimental Biology vol 6 no 4 pp 232ndash247 1968

[61] Temjenmongla and A K Yadav ldquoAnticestodal efficacy offolklore medicinal plants of Naga tribes in north-east IndiardquoAfrican Journal of Traditional Complementary and AlternativeMedicines vol 2 pp 129ndash133 2005

[62] T V Tangpu and A K Yadav ldquoAnticestodal efficacy of Psidiumguajava against experimental Hymenolepis diminuta infectionin ratsrdquo Indian Journal of Pharmacology vol 38 no 1 pp 29ndash32 2006

[63] R Singh A Mehta P Mehta and K Shukla ldquoAnthelminticactivity of Rhizome extracts of Curcuma longa and Zingiberofficinalerdquo International Journal of Pharmacy and Pharmaceu-tical Sciences vol 3 no 2 pp 236ndash237 2011

[64] M K Asha D Prashanth B Murali R Padmaja and A AmitldquoAnthelmintic activity of essential oil of Ocimum sanctum andeugenolrdquo Fitoterapia vol 72 no 6 pp 669ndash670 2001

[65] J B Githiori J Hoglund P J Waller and R L Baker ldquoTheanthelmintic efficacy of the plantAlbizia anthelmintica againstthe nematode parasites Haemonchus contortus of sheep andHeligmosomoides polygyrus of micerdquo Veterinary Parasitologyvol 116 no 1 pp 23ndash34 2003

[66] N M Enwerema J I Okoguna C O Wambebea D A Oko-rieb and P A Akahc ldquoAnthelmintic activity of the stem barkextracts of Berlina grandiflora and one of its active principlesBetulinic acidrdquo Phytomedicine vol 8 pp 112ndash114 2001

[67] Z Iqbal M Lateef A Jabber M N Ghayur and A HGilani ldquoIn vitro and in vivo anthelmintic activity of Nicotianatabacum L leaves against gastrointestinal nematodes of sheeprdquoPhytotherapy Research vol 20 no 1 pp 46ndash48 2006

[68] Z Iqbal M Lateef A Jabbar G Muhammad and M N KhanldquoAnthelmintic activity of Calotropis procera (Ait) Ait F flowersin sheeprdquo Journal of Ethnopharmacology vol 102 no 2 pp 256ndash261 2005

Submit your manuscripts athttpwwwhindawicom

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ToxinsJournal of

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MEDIATORSINFLAMMATION

of

Page 3: Mallotus philippinensis Muell. Arg (Euphorbiaceae ...

BioMed Research International 3

Table 2 Cardenolide and its derivatives

O

O

O

Me

OH

H

H

HR1

R2

No Name R1 R2 References1 Coroglaucigenin CH2OH H [8]2 Coroglaucigenin L-rhamnoside CH2OH L-rham [8]3 Corotoxigenin CHO H [8]4 Corotoxigenin L-rhamnoside CHO L-rham [8]

Kamala are also used in external applications to promote thehealing of ulcers and woundsThey are used to treat parasiticaffections of the skin like scabies ringworm and herpes

23 Common Adulterants Glandular hair powder of Mphilippinensis is commonly adulterated with Annato dye(Bixa orellana Linn) ferric oxide brick dust and ferruginoussand Casearia tomentosa (stem bark powder) Carthamustinctorius (flower powder) Ficus benghalensis (fruit powder)and Flemingia macrophylla (hairs of fruits) are also reportedto be used as adulterant or substitute of Kampillaka [7]

3 Chemical Constituents

Major phytochemicals present in this genus contain dif-ferent natural compounds mainly phenols diterpenoidssteroids flavonoids cardenolides triterpenoids coumarinisocoumarins and many more to discover Present knowl-edge about this endangered species of medicinal plant isstill limited with respect to its phytochemistry and biologicalactivity However some researchers have contributed towardsisolation of some novel constituents and their activity One ofthe major chemical constituent that is rottlerin ofM philip-pinensis is listed below with its chemical structure and itsmajor biological activities along with other phytochemicals(Figure 18)

31 Cardenolides M philippinensis seeds contain cardeno-lides The seeds of M philippinensis were found to containafter fermentation four cardenolides (Table 2) of whichtwo were newly reported corotoxigenin L-rhamnoside andcorogl-aucigenin L-rhamnoside [8]

32 Triterpenoids Some Mallotus species were found tohave a characteristic feature of pentacyclic triterpenoids witha 66665 ring system The petroleum ether extract of

Table 3 Lupeol and its derivatives

H

H

H

H

CH3

CH3

CH3CH3

CH3

CH2

OR

H3C

H3C

No Name R1 References6 Lupeol-3-acetate Ac [9]7 Lupeol H [9]

AcO

OHH

H

H

HCH3

CH3

CH3CH3

CH2

H3C

H3C

Figure 1 Betulin-3-acetate

HHH

O

CH3

CH3

CH3

CH3

CH3

CH3

CH3

H3C

Figure 2 Friedelin

the heartwood of M philippinensis yielded triterpenoidsbetulin-3-acetate (Figure 1) as a major compound lupeolacetate (Table 3) and lupeol (Table 3) [9] Friedelane-typetriterpenoids are very common inMallotus species Friedelin(Figure 2) was obtained from the stem bark of M philip-pinensis [10] Most of the genera of family Euphorbiaceaesuch as Drypetes [11] or Celaenodendron [12] also containfriedelin in rich amount Friedelin is common and is alsofound in plants from other orders Other known pentacyclicterpenoids that is acetylaleuritolic acid (Figure 3) found tobe reported in the petroleum and ether extracts from barkof M philippinensis [9] The first olean-18-ene triterpeneoxidized at C-22 (Figure 4) was isolated from the stem bark

4 BioMed Research International

AcOH

H

H

CH3

CO2H

H3C

H3C

CH3 CH3

CH3

CH3

Figure 3 Acetylaleuritolic acid or aleuritic acid acetate

H

H

H

O

O

OH

CH3

CH3

CH3 CH3

CH3

CH3

H3C

H3C

H3C

Figure 4 3b-Acetoxy-22b-hydroxyolean-18-ene

of M Philippinensis [10] Apart from above triterpeniodsursane-type triterpenoid a-amyrin (Figure 5) reported fromthe petroleum ether and ethereal extracts ofM philippinensisbark [9]

33 Steroids Common steroid b-sitosterol (Figure 6) wasisolated from petroleum ether extracts of the heartwood andbark ofM philippinensis [9] Daucosterol was obtained fromether extract from bark ofM philippinensis [9]

34 Phenolic Compounds Isocoumarins Bergenin(Figure 7) an isocoumarin was isolated in 1972 fromthe heartwood ofM philippinensis This compound was alsoobtained from the bark and the leaves of M philippinensis[9]

Two new chalcone derivatives (flavonoids) kamalachal-cones A and B (Figures 8-9) with a unique ring systemcaused by dimerization between a dimethylchromene ringand a phenoxyl group were isolated from kamala (Mphilippinensis) [13] Three other novel chalcone derivativesmallotophilippens C D and E (Figures 10 11 12 13 and 14)were isolated from the fruits ofM philippinensis [14] lignanschalcones and dimeric chalcone derivatives [15]

Four phloroglucinol derivatives (kamalins) rottlerin andisorallorottlerin (Figures 15 and 16) were isolated from Mphilippinensis [16] Isorottlerin (Figure 17) was also men-tioned inM philippinensis [17]

Fruit and bark of plant contain condensed tanninsresponsible for antioxidant activity Methanolic bark extract

H

H

H

HO

CH3

CH3

CH3

CH3

CH3CH3

H3C

H3C

Figure 5 120572-Amyrin

H

H

H

H

OR

CH3

CH3

H3Ci-Pr

Et

Figure 6 120573-Sitosterol

OH

OHOH

OH

HO

MeO

O

O

O

Figure 7 Bergenin

O

O

O

O O

CH3

CH3

CH3

CH3

H3C

H3C

H

H

HHO

HO OH

Figure 8 Kamalachalcone A

BioMed Research International 5

O

O

O

O

O O

CH2

CH3

CH3

CH3

CH3

H3C

H3C

H3C

H

H

H

HO

HO

HO

HO OH

OH

Figure 9 Kamalachalcone B

O O

OOH

OHOH

HO HO 2

3

45

6

78

9

10

1112

1314

15

1998400

2998400

3998400

4998400

5998400

6998400

7998400

8998400

Figure 10 Mallotophilippen A or 1-[57-dihydroxy-22-dimethyl-6-(246-trihydroxy-3-isobutyryl-5-methyl-benzyl)-2H-chromen-8-yl]-2-methyl-butan-1-one

of M philippinensis subjected to characterization throughcolumn chromatography on a Sephadex LH-20 column usingethanol and acetone-water as the mobile phases tanninsand phenols were quantified Bark extract contains 541mggof total phenolics and infractions ranging from 54mgg(fraction I) to 927mgg (fraction VI) and condensed tanninswere detected in fractions IIndashVI [18 19] In 1989 leaves ofM philippinensis were reported for tannins and other relatedcompounds by Saijo et al [20]

35 Other Compounds Unsaturated fatty acids that is triply-unsatured hydroxy acid kamlolenic acid different fatty acidsand glyceride [21] have been reported from Kamala (Mphilippinensis) seed oil

Resinous coloured material contains active parts of rott-lerin and isorottlerin It also contains homorottlerine red role50 yellow role 5 manure 2 volatile oils tannin gumcitric acid and oxalic acid

4 Pharmacological Activities

41 Antifilarial Activity The effect of aqueous and alcoholicleave extracts of M philippinensis (Lam) Muell was studiedon the spontaneous movements of the whole worm and

O O

OOH

OHOH

HO HO 2

3

45

6

78

9

10

1112

1314

15

1998400

2998400

3998400

4998400

5998400

6998400

7998400

Figure 11 Mallotophilippen B or 1-[6-(3-acetyl-246-trihydroxy-5-methyl-benzyl)-57-dihydroxy-22-dimethyl-2H-chromen-8-yl]-2-methyl-butan-1-one

OH

OH

HO

OHO

Figure 12 Mallotophilippen C or (1-[6-(37-dimethyl-octa-26-dienyl)-57-dihydroxy-22-dimoethyl-2H-chromen-8-yl]-3-(4-hy-droxy-phenyl)-propenone) R = H

OH

OH

OHO

OHO

Figure 13 Mallotophilippen D or 3-(34-dihydroxy-phenyl)-1-[6-(37-dimethyl-octa-26-dienyl)-57-dihydroxy-22-dimethyl-2H-chromen-8-yl]-propenone R = OH

nerve-muscle (nm) preparation of Setaria cervi and on thesurvival of microfilariae in vitro Both the extracts result ininhibition of spontaneous motility of whole worm and thenm preparation of S cervi characterized by initial stimula-tion followed by depression in amplitude The tone and rateof contractions remained visibly unaffected Aqueous extractat higher concentration showed immediate reduction in toneThe concentration required to inhibit the movements of nmpreparation was 15th for aqueous and 111th for alcoholicextract compared to that for the whole worm suggesting acuticular permeability barrier The stimulatory response ofacetylcholine was blocked by aqueous extract onwhole worm

6 BioMed Research International

OH

OH

OH

O

OHO

Figure 14 Mallotophilippen E or 1-[57-dihydroxy-2-methyl-6-(3-methyl-but-2-enyl)-2-(4-methyl-pent-3-enyl)-2H-chromen-8-yl]-3-(34-dihydroxy-phenyl)-propenone

OH

OH

OHOH

O

O

O

HO

Figure 15 Rottlerin

movements On the microfilariae the LC50and LC

90were 18

and 20 ngmL for aqueous and 12 and 15 ngmL for alcoholicextracts respectively [2] Further study will be required toevaluate the same activity with its phytochemicals

42 Antifertility Activity Seeds extract of M philippinensisexhibits adverse effects on different reproductive parametersof female rats According to the study extract reducesserum FSH and LH levels probably by affecting hypotha-lamicpituitary axis in experimental animals This reducedlevel may affect follicular development quality of ovulatedeggs corpus luteum formation estrus cycle andmaintenanceof pregnancy in rats [22] This antifertility effect of plantextract is supposed to be caused by rottlerin (Figure 15) aphloroglucinol derivative Acetyl rottlerin may be active butisorottlerin (Figure 17) is either inactive or slightly active [23]Effect of pure rottlerin can be further studied so as to clarifythe potential of phloroglucinol derivatives

43 Antibacterial and Antifungal Activity A series of 61Indian medicinal plants belonging to 33 different familiesused in various infectious disorders were screened for theirantimicrobial properties Screening was carried out at 1000and 500 120583gmL concentrations by agar dilution methodagainst Bacillus cereus varmycoides Bacillus pumilus Bacillussubtilis Bordetella bronchisepticaMicrococcus Luteus Staphy-lococcus aureus Staphylococcus epidermidis Escherichia coli

OH

OH

O

O

O

HO

HO

HO

Figure 16 Isoallorottlerin

OH

OH

O

O

O

OHO

HO

Figure 17 Isorottlerin

Klebsiella pneumonia Candida albicans and Saccharomycescerevisiae Twenty-eight plant extracts showed activity againstat least one of the test organisms used in the screeningOn the basis of the results obtained study concludes thatthe crude extracts of M philippinensis exhibited significantantimicrobial activity [3] and properties that support folk-loric use in the treatment of some diseases as broad-spectrumantimicrobial agents Steam bark of plant and its chloroformfractions and the methanolic extract significantly inhibitthe pathogenic bacteria with significant zones of inhibitioncomparable to the standard drug used However the hexanicextract did not show any significant activity [24] Glandularhair of fruits of Mallotus exhibits significant antibacterialactivity against human pathogenic bacteria withMIC ranging15ndash20mgmL This extract does not show any inhibitionagainst different species of candida This shows that fruitextract possesses antibacterial activity without any antifungalpotential The results of the study may justify the use of theplant against bacterial pathogens This probably explains theuse of these plants by the indigenous people against a numberof infections [25]

However ethanolic extract shows potent anti-Heli-cobacter pylori activity at the concentration of 156ndash312mgLagainst eight H pylori strains Further purification of extractrevealed that rottlerin exhibits potent bactericidal effectwith minimal bactericidal concentration (MBC) of 312ndash625mgL against different resistant strains of clarithromycin

BioMed Research International 7

M philippinensis

Rottlerin

Fruit

H3C

HO

HO

OH OH

OH

O

O

O

CH3

CH3

CH3

Antifertility

Antimicrobial

Protein inhibition

Antituberculosis activity

Antiallergic activity

Antiproliferative activity

Antiparasitic (cestodal)

Figure 18 Rottlerin and its major biological activities

and metronidazole including Japanese and Pakistani strains[17]

44 Anti-Inflammatory and Immunoregulatory ActivityChalcones derivatives from the fruits of M philippinensisand mallotophilippens C D and E (Figures 12 13 and14) inhibit nitric oxide (NO) production and inducibleNO synthase (iNOS) gene expression by a murinemacrophage-like cell line (RAW 2647) which was activatedby lipopolysaccharide (LPS) and recombinant mouseinterferon-gamma (IFN-gamma) Further investigationssuggest the downregulation of cyclooxygenase-2 geneinterleukin-6 gene and interleukin-1b gene expressionThe above results show that these chalcones have goodanti-inflammatory and immunoregulatory effects [26]

45 Antioxidant Activity and Antiradical Activity Differentfractions of bark and fruit of Mallotus were studied forits total antioxidant activity (TAA) and antiradical activityagainst DPPH on a Sephadex LH-20 column using ethanoland acetone-water asmobile phase Among different extractsbark fraction showed the strongest antiradical activity (TAAvaluemdash527 mmol Trolox equivg) and reducing powerAnother extract that is phenolic fraction shows TAAranging from 058mmol Troloxg (fraction I) to 682mmolTroloxg (fraction IV) this is the strongest fraction showingantiradical activity against DPPH and reducing power TAAof other extracts ranged from 005 to 179mmol Troloxequivg [18 19]

46 Protein Inhibition Implicated in Cancer Processes Proteinkinase is inhibited with some specificity for PKC by rottlerina compound isolated from Mallotus Inhibition of PKCappears due to a strong competition between rottlerin andATP CaM-kinase III is suppressed by rottlerin as effectivelyas PKC 120575 among different protein kinases tested Novelinhibition property and improved selectivity for a distinctPKC isoenzyme of rottlerin are suggestive from its chemicalstructure [27 28] Rottlerin is also very potent in blockingother kinases including AktPKB and p38 MAPK [29ndash31] Italso inhibits human T cell responses [32] reduces MUC5ACexpression in human epithelial cells [33] abrogates reactiveoxygen species production in hepatic stellate cells [34] andprevents histamine-induced H1-receptor gene expression inHeLa cells [35] However still very limited information isavailable of rottlerin towards cancer disease and its mecha-nism of action

47 Hepatoprotective Activity Methanolic extract of Mphilippinensis leaves decreases the CCl

4-induced elevation in

biochemical parameters (SGOT SGPT SALP direct biliru-bin total bilirubin andMDA) on pretreatment at doses 100ndash200mgkg and also reversed the functional and antioxidantparameters This study suggests that leave extract was effec-tive in functional improvement of hepatocytes Histopatho-logical studies also suggest the hepatoprotective activity ofplant [36]

48 In Vitro Cytotoxicity against Human Cancel Cell Glan-dular hair extract of Mallotus fruit powder was assayed

8 BioMed Research International

(a) (b)

(c) (d)

(e)

Figure 19 Mallotus philippinensis (a) Mature plant (b) leaf (c) initial inflorescence of seed setting (d) mature fruits twig (e) mature fruitwith seed

against 14 human cancer cell lines among different fractions95 ethanolic extract showed the highest cytotoxic effect ascompared to 50 ethanolic and aqueous portion Furtherthe chromatographic analysis of the said fraction afforded apolyphenolic molecule rottlerin inMallotus plant [37]

49 Anticestodal ActivityVeterinary Applications M philip-pinensis fruit was found to be very effective against gas-trointestinal cestodes in Beetal goats and other ruminantsComparative anticestodal efficacies of single oral dose treat-ments with the powdered fruit ofM philippinensis (125 250and 375mgkg) its water or methanol extracts (equivalent to375mgkg) and the total glycosides (25 50 and 100mgkg)were determined in naturally cestode-infected Beetal goats[38] An ethnobotanical survey has been conducted foranthelmintics in ruminants so as to document the plantsused to treat and control helminthes Mallotus has beenfrequently used to treat helminthosis in ruminants [39] M

philippinensis fruit extract of 800mgkg twice daily for 3days was observed to have curative efficacy against matureadult worms of Hymenolepis diminuta The total follow-upperiod of 90 days did not show any further excretion of eggsin the faeces of treated rats Praziquantel at the dosage of5mgkg also produced a similar effect [40] In vitro scolicidalactivity ofM philippinensis (Lam)Muell Arg fruit glandularhair extract against hydatid cyst Echinococcus granulosusprotoscoleces at concentrations 10 and 20mgmL shows themortality rate 97 to 99 respectively for 60min treatmentwhile up to 93 mortality was observed with 20mgmLfor only 10min treatment This proves that the extract hassignificant scolicidal activity with almost no associated sideeffects [41] In vivo animal model experiment will be furtherrequired to prove its effect against Hydatid cyst

410 Purgative Activity and Anthelmintic Activity A signifi-cant purgative effect after an oral dose (120mgkg) in rats was

BioMed Research International 9

assessed from resins isolated from plant Its effect was evalu-ated from the weight of faeces as well as from surface areaof blotting paper soaked by liquid faeces The anthelminticeffect on tape worm was evaluated in albino rates fromthe resin of the plant showed lethal effect of 3569 and7821 respectively in small intestine in concentrations 60and 120mgkg respectively [42 43]

411 Antituberculosis Activity Organic extract of plant afterbioassay-directed fractionation yields five compounds themost active of which againstMycobacterium tuberculosis wasa new compound 8-cinnamoyl-57-dihydroxy-22-dimethyl-6-geranylchromene for which the name mallotophilippenF is suggested The second compound 8-cinnamoyl-22-dimethyl-7-hydroxy-5-methoxychromene was isolated froma natural source for the first time while the remaining threecompounds rottlerin isoallorottlerin or isorottlerin andthe so-called ldquored compoundrdquo 8-cinnamoyl-57-dihydroxy-226-trimethylchromene had been already isolated fromthis plant Isolated compounds were identified by 2D-NMRand C-13 NMR [44] Ethanolic extract of plant was assayedfor antimycobacterial activity against M smegmatis by discdiffusion assay Further antituberculosis potential of leavesextract was identified by radiometric BACTEC assay resultrevealed that ethanolic extract ofM philippensis showed anti-tuberculosis activity against virulent and avirulent strains ofM tuberculosis H37Rv andM tuberculosis H37Ra with min-imum inhibitory concentrations of 025 and 0125mgmLminus1respectively The inhibition in growth index values of Mtuberculosis was observed in the presence of ethyl acetatefraction at a minimum concentration of 005mgmLminus1 Itsuggests that ethanolic and ethyl acetate fraction of plantpossesses significant antimycobacterial activity [45] Steambark of M philippinensis has also been reported for itsantitumor promoting effect which was due to the presenceof 3120572-Hydroxy-DA-friedooleanan-2-one [46]

412 Antiallergic Activity M philippinensis fruit containstwo new phloroglucinol derivatives mallotophilippensA and B (Figures 10 and 11) which were identified usingchemical and spectral data as 1-[57-dihydroxy-22-di-methyl-6-(246-trihydroxy-3-isobutyryl-5-methyl-benzyl)-2H-chromen-8-yl]-2-methyl-butan-1-one and 1-[6-(3-Acetyl-246-trihydroxy-5-methyl-benzyl)-57-dihydroxy-22-dim-ethyl-2H-chromen-8-yl]-2-methyl-butan-1-one respe-ctively These compounds inhibited the production ofnitric oxide (NO) and inducible NO synthase (iNOS) geneexpression by a murine macrophage-like cell line (RAW2647) which was activated by lipopolysaccharide (LPS)and recombinant mouse interferon-g (IFN-g) Furtherphloroglucinol derivatives inhibit histamine release from ratperitoneal mast cells induced by compound 4880This studysuggests its anti-inflammatory activity [47] Rottlerin hasbeen tested in animal models of IgE-dependent anaphylaxisand the antiallergic mechanisms of action in mast cellsAntiallergic action of rottlerin has been tested in passivecutaneous anaphylaxis and passive systemic anaphylaxismouse models and in anaphylactic contraction of bronchial

rings isolated from sensitized guinea pigs This experimentsproves antiallergic effect of rottlerin by blocking IgE-inducedmast cell degranulation This report suggests the use ofrottlerin in mast cell-mediated allergic disorders includingurticaria and allergic asthma [48]

413 Anti-Leukaemic Activity Root extract ofM philippinen-sis was tested on human promyelocytic leukemia HL-60 cellproliferation cell cycle regulators and apoptosis in order toinvestigate its antileukemic effect Hexane fraction showedpromising toxicity against p53-deficient HL-60 cells (IC

50

15mg dry roots equivalentmL medium) after 72 h andinterestingly inhibition of cell proliferation was preceded bythe upregulation of the protooncogenes Cdc25A and cyclinD1 within 24 hours suggesting its antileukemic effect inHL-60 cells After isolation and identification by GC-MSpolyphenols were the main compounds of the hexane extractthat inhibited proliferation and induced apoptosis [49]

414 Antiproliferative Activity Antiproliferative effect wasevaluated against Thp-1 cell lines from the isolated com-pounds of M philippinensis fruit extract in which 41015840-hydroxyrottlerin showed 54 growth inhibition ofThp-1 cellline [50] Other isolated compounds were also tested againstdifferent fungi andwere found to be very effective IC

50values

415 Anti-HIV Activity Four phloroglucinol derivativesnamed mallotophenone (5-methylene-bis-26-dihydroxy-3-methyl-4-methoxyacetophenone) mallotochromene (8-acetyl-57-dihydroxy-6-(3-acetyl-24-dihydroxy-5-methyl-6-methoxybenzyl)-22-dimethylchromene) mallotojaponin(3-(33(dimethylallyl) S-(3(acetyl-24-dihydroxy-5-methyl-6-methoxybenzyl)-phloracetophenone) andmallotolerin (3-(3-methyl-2-hydroxybut-3-enyl)-5-(3-acetyl-24-dihydroxy-5-methyl-6-methoxybenzyl)-phloracetophenone) weretested for their ability to inhibit the activity of humanimmunodeficiency virus- (HIV-) reverse transcriptaseThe mode of inhibition of mallotojaponin was foundto be competitive with respect to the template primer(rA)n (dT)12ndash18 and noncompetitive with respect to thetriphosphate substrate dTTPThe Ki value of mallotojaponinfor HIV-reverse transcriptase was determined to be 61 120583M[51]

416 Antitumor Activity Four known friedelane-type trit-erpenoids friedelin 3-hydroxy-DA-friedoolean-3-en-2-one 2120573-hydroxy-DA-friedooleanan-3-one and 3120572-hy-droxy-DA-friedooleanan-2-one and two known lupane-type triterpenoids lupeol and betulin were isolated fromthe stem bark of M philippinensis and were tested fortheir inhibitory effects on Epstein-Barr virus early antigen(EBV-EA) activation induced by 12-O-tetradecanoylphorbol13-acetate (TPA) The inhibitory effect of compounds 2(IC50

= 292mol ratio32 pmolTPA) and 4 (IC50

= 288) wasstronger than those of the other compounds tested and thepositive control curcumin (IC

50= 343) Compound 3120572-

hydroxy-DA-friedooleanan-2-one strongly inhibited mouse

10 BioMed Research International

skin tumor promotion in an in vivo two-stage carcinogenesismodel [46]

417 Wound Healing and Mesenchymal Stem Cell (MSC)Proliferation Bark extract ofMallotus philippinensis has beentested in vitro for wound healing activity by examining theproliferation and migration of MSCs KUM6 cells prolifer-ation and migration have been enhanced at 016ndash4 120583gmLand unregulated the activity of MSCs by secreting variouscytokines to wounded site from bone marrow to systemiccirculation and finally remodel wounded tissues [52]

418 Toxicities Seeds of M philippinensis ethereal extracthave adverse effect on various parameters of female rats Eventhe extract reduces serum levels of gonadotropins in treatedanimals at high dose of 100mgkg body weight Reducedweights of ovary and uterus follicular development andincreased atretic follicular in the ovary are due to subnormallevels of steroid hormones Thus pregnancy is very difficultin female rats treated with kamala seed extract [22]

419 Colouring Agent-Dye Glandular hairs of fruit aremostly used as an orange dye for silk [53 54]

5 Pharmacognostic Evaluation ofMallotus philippinensis

Morphological study shows that fruit depresses globoseand is three-lobed capsule 5ndash7mm times 8ndash10ndash12mm stellate-puberulose and with abundant orange or reddish glan-dular granules Seeds are subglobose and black in colorOrganoleptic property of the red fruit shows that it is tastelessand odourless Microscopic description showed the presenceof epicarp which contained a compactly packed layer ofmucilaginous cells and mesocarp composed of columnarcells which are closely arranged Its polygonal cells are com-pactly arranged in 2-3 layers Presence of lignified vasculararrangement has been observed in the transverse section [55]

6 Conclusion and Future Perspective

Medicinal plants have been clinically used and its interest hasbeen dramatically increased over the past decades throughoutthe world and its formulations are increasingly cited inmedia Daily consumption of the natural products and theirformulations by an extensive number of patients lead toserious concern for scientist to study its efficacy and safetyBecause of extensive use and its benefits natural productsin many countries are regulated both as medicinal productsand as food supplements often labeled as natural foodsupplements

Traditional use and its growing demand for Mallotusphilippinensis and its other species lead to compile this reviewand commented on the current knowledge provided byclinical and preclinical research on the effect of this plant

Mallotus philippinensis has been widely used as tradi-tional medicine in several parts of countries including IndiaEvery part of this plant possesses its specific medicinal prop-erties and is usedmainly in ayurveda to fight against intestinalworms in domestic and grazing animals when administeredwith jaggeryHowever only a few reports are attributed to thisplant and its different parts and there is a large scope for inves-tigation Hence it is required to explore more of its potentialwithin the field of medicinal and pharmaceutical sciences fornovel and fruitful application of this plant in form of naturalformulation Along with this medicinal importance thisplant is used against human pathogens including H pylorianti-inflammatory activity antioxidant antiradical proteininhibition hepatoprotective antiallergic anti-HIV activityand many more Phytochemical investigation revealed that alarge number phenol derivatives and several miscellaneouscompounds from different classes have been isolated fromthis species The phenols diterpenoids steroids flavonoidscardenolides triterpenoids coumarins and isocoumarinsare mostly distributed in all parts of the plant The othermajor isolated pure compounds from this species mostlybelong to phenolic group exhibiting most of the biologicalactivity Various types of extracts from different parts andsingle compounds derived from this species have beenfound to possess biological activities including antioxidantantimicrobial anti-inflammatory cytotoxicity and immunemodulatory Fruit and bark of plant contain condensed tan-nins responsible for antioxidant activity Somenovel chalconederivatives mallotophilippens C D and E were isolatedfrom the fruits of M philippinensis Mallotoxin or rottlerinhas great anticancerous potential Among the ever-anticanceragents rottlerin appears to have great potentiality for beingused in chemotherapy Rottlerin will become a potentialmolecule for research in future to treat cancerous cell as itwill affect cell machineries involved in apoptosis survivaland autophage This suggests the view that this species haspotential to be a beneficial chemotherapeutic remedy

Although the data and other reports provided that thismedicinal plant is of great biological use in different phar-macological activities including anticancer further researchis needed in different areas regarding the toxicity and efficacyof pure phytochemicals isolated from different parts of thisplant More data will be needed from preclinical and clinicalstudies on humans to clarify its potency and safety aslack of knowledge with respect to its adverse effects andmethodological accuracy in the literature limits towardsits standardized formulation Furthermore the mechanismof action of the phytochemicals and extract of Mallotusphilippinensis is unclear more exhaustive studies will beperformed to explore its mechanism and structure activityrelationship among various constituents

In conclusion this review confirms the great potential ofMallotus philippinensis As very limited information is stillknown for this species it leads us to continue the study ondifferent species of Mallotus plant and its interesting phar-macological properties Further natural product chemistryof isolated moiety and its structural analysis of compounds

BioMed Research International 11

responsible for these activities will be an interesting field ofresearch

Conflict of Interests

The authors declare that there is no conflict of interests re-garding the publication of this paper

Acknowledgment

The authors gratefully acknowledge the financial supportprovided by CSIR Government of India New Delhi forawarding SRF in the form of research fellowship

References

[1] C-J Widen and H S Puri ldquoNatural occurrence and chemicalvariability of phloroglucinols inKamalardquoPlantaMedica vol 40no 3 pp 284ndash287 1980

[2] R Singh K C Singhal and N U Khan ldquoAntifilarial activity ofMallotus philippinensisLam on Setaria cervie (Nematoda Filar-ioidea) in-vitrordquo Indian Journal of Physiology andPharmacologyvol 41 no 4 pp 397ndash403 1997

[3] V P Kumar N S Chauhan H Padh and M Rajani ldquoSearchfor antibacterial and antifungal agents from selected Indianmedicinal plantsrdquo Journal of Ethnopharmacology vol 107 no2 pp 182ndash188 2006

[4] S Shrikumar and T K Ravi ldquoApproaches towards developmentand promotion of herbal drugsrdquo Pharmaceutical Reviews vol 1no 1 pp 180ndash183 2007

[5] C Orwa A Mutua and R Kindt ldquoAgroforestree Database atree reference and selection guiderdquo Version 4 0 2009

[6] K Usmanghani A Saeed and M T Alam ldquoIndusynicMedicine Karachirdquo Research Institute of Indusyunic Medicinevol 1997 pp 285ndash287 1997

[7] F Ahmad and S Hashmi ldquoAdulteration in commercial Kamila(Mallotus philippinensisMuell) an anthelmintic drug of reputerdquoHamdard Medicus vol 38 pp 62ndash67 1995

[8] K D Roberts E Weiss and T Reichstein ldquoGlycosides andaglycons CCLII Cardenolides of the seed of Mallotus philip-pinensisrdquo Helvetica Chimica Acta vol 46 pp 2886ndash2893 1963

[9] M Bandopadhyay V K Dhingra and S K Mukerjee ldquoTriter-penoid and other components of Mallotus philippinensisrdquo Phy-tochemistry vol 11 no 4 p 1511 1972

[10] S P Nair and J Madhusudana Rao ldquoKamaladiol-3-acetate fromthe stem bark of Mallotus philippinensisrdquo Phytochemistry vol32 pp 407ndash409 1993

[11] J DWansi JWandjiW A Kamdem et al ldquoTriterpenoids fromDrypetes chevalieri Beille (Euphorbiaceae)rdquo Natural ProductResearch vol 20 no 6 pp 586ndash592 2006

[12] P Castenada A Bahena and E Garcia ldquoChemical studieson Mexican plants used in traditional medicine XXIX Sec-ondary metabolites from the stem bark of Celaeno-dendronmexicanumrdquo Journal of Natural Products vol 56 pp 1575ndash15791993

[13] T Tanaka T Ito M Iinuma Y Takahashi and H NaganawaldquoDimeric chalcone derivatives from Mallotus philippinensisrdquoPhytochemistry vol 48 no 8 pp 1423ndash1427 1998

[14] T M Nguyen V M Chau V K Phan et al ldquoStudy on chemicalconstituents of the leaves of Mallotus philippinensisrdquo Tap ChiHoa Hoc vol 48 pp 352ndash357 2010

[15] M Furusawa Y Ido T Tanaka et al ldquoNovel complex flavonoidsfrom Mallotus philippinensis (Kamala tree)rdquo Helvetica ChimicaActa vol 88 no 5 pp 1048ndash1058 2005

[16] M Lounasmaa C J Widen C M Tuuf and A HuhtikangasldquoOn the phloroglucinol derivatives of Mallotus philippinensisrdquoPlanta Medica vol 28 no 1 pp 16ndash31 1975

[17] S F H Zaidi I Yoshida F Butt et al ldquoPotent bactericidal con-stituents from Mallotus philippinensis against clarithromycinand metronidazole resistant strains of Japanese and Pakistanihelicobacter pylorirdquo Biological and Pharmaceutical Bulletin vol32 no 4 pp 631ndash636 2009

[18] M Arfan H Amin M Karamac et al ldquoAntioxidant activityof extracts of Mallotus philippinensis fruit and barkrdquo Journal ofFood Lipids vol 14 no 3 pp 280ndash297 2007

[19] M Arfan K Hazrat and K Magdalena ldquoAntioxidant activityof phenolic fractions of Mallotus philippinensis bark extractrdquoJournal of Food Science vol 27 no 2 pp 109ndash117 2009

[20] R Saijo G Nonaka and I Nishioka ldquoTannins and related com-pounds LXXXVIII Isolation and characterization of hydrolyz-able tannins fromMallotus japonicus (Thunb)Mueller-Arg andM philippinensis (Lam)Mueller-ArgrdquoChemical amp Pharmaceu-tical Bulletin vol 37 no 11 pp 2940ndash2947 1989

[21] S C Gupta S S Gupta and J S Aggarwal ldquoChemical exami-nation of the seeds of Mallotus philippinensis III Constitutionof kamlolenic acid isolated from the oilrdquo Journal of Scientific ampIndustrial Research vol 12 pp 240ndash242 1953

[22] S C Thakur S S Thakur S K Chaube and S P Singh ldquoAnetheral extract of Kamala (Mallotus philippinensis (Moll Arg)Lam) seed induce adverse effects on reproductive parametersof female ratsrdquo Reproductive Toxicology vol 20 no 1 pp 149ndash156 2005

[23] M L Gujral D R Varma K N Sareen and A K Roy ldquoOralcontraceptives II Antifertility effect ofMallotus philippinensisrdquoIndian Journal of Medical Research vol 48 pp 52ndash58 1960

[24] KMoorthy K Srinivasan C Subramanian CMohanasundariand M Palaniswamy ldquoPhyto-chemical screening and antibac-terial evaluation of stem bark of Mallotus philippinensis varTomentosusrdquoAfrican Journal of Biotechnology vol 6 no 13 pp1521ndash1523 2007

[25] M Gangwar D Kumar R Tilak et al ldquoQualitative phy-tochemical characterization and antibacterial evaluation ofglandular hairs ofMallotus philippinensis fruit extractrdquo Journalof Pharmacy Research vol 4 no 11 pp 4214ndash4216 2011

[26] A Daikonya S Katsuki and S Kitanaka ldquoAntiallergic agentsfrom naturalsources 9 Inhibition of nitric oxide productionby novel chalcone derivatives from Mallotus philippinensis(Euphorbiaceae)rdquo Chemical amp Pharmaceutical Bulletin vol 52no 11 pp 1326ndash1329 2004

[27] M Gschwendt H J Muller K Kielbassa et al ldquoRottlerina novel protein kinase inhibitorrdquo Biochemical and BiophysicalResearch Communications vol 199 no 1 pp 93ndash98 1994

[28] Y F Liao Y C Hung W H Chang et al ldquoThe PKC deltainhibitor rottlerin induces apoptosis of haematopoietic celllines through mitochondrial membrane depolarization andcaspasescascaderdquo Life Sciences vol 77 no 6 pp 707ndash719 2005

[29] H S Kang E K Park K H Kim et al ldquoReceptor activatorof nuclear factor-kappa B is induced by a rottlerin-sensitiveand p38 MAP kinase-dependent pathway during monocytedifferentiationrdquoMolecules and Cells vol 17 no 3 pp 438ndash4452004

12 BioMed Research International

[30] S P Soltoff ldquoRottlerin an inappropriate and ineffectiveinhibitor of PKC120575rdquo Trends in Pharmacological Sciences vol 28no 9 pp 453ndash458 2007

[31] Y Choi D K Kim S S Kang J K Sonn and E J Jin ldquoIntegrinsignaling and cell spreading alterations by rottlerin treatment ofchick limb bud mesenchymal cellsrdquo Biochimie vol 91 no 5 pp624ndash631 2009

[32] C Springael S Thomas S Rahmouni et al ldquoRottlerin inhibitshuman T cell responsesrdquo Biochemical Pharmacology vol 73 no4 pp 515ndash525 2007

[33] J H Choi Y P Hwang E H Han et al ldquoInhibition of acrolein-stimulated MUC5AC expression by Platycodon grandiflorumroot-derived saponin in A549 cellsrdquo Food and Chemical Toxi-cology vol 49 no 9 pp 2157ndash2166 2011

[34] E L M Guimaraes C Empsen A Geerts and L A vanGrunsven ldquoAdvanced glycation end products induce produc-tion of reactive oxygen species via the activation of NADPHoxidase in murine hepatic stellate cellsrdquo Journal of Hepatologyvol 52 no 3 pp 389ndash397 2010

[35] H Mizuguchi T Terao M Kitai et al ldquoInvolvement of pro-tein kinase C120575extracellular signal-regulated kinasepoly(ADP-ribose) polymerase-1 (PARP-1) signaling pathway in histamine-induced up-regulation of histamine H1 receptor gene expres-sion in HeLa cellsrdquo Journal of Biological Chemistry vol 286 no35 pp 30542ndash30551 2011

[36] S Ramakrishna K M Geetha P V V S Bhaskar gopalR P Kumar C P Madav and L Umachandar ldquoEffect ofMallotus PhilippinensisMuell-Arg leaves against hepatotoxicityof Carbon tetrachloride in ratsrdquo International Journal of Phar-maceutical Sciences and Research vol 2 pp 74ndash83 2011

[37] V Sharma ldquoA polyphenolic compound rottlerin demonstratessignificant in vitro cytotoxicity against human cancer celllines isolation and characterization from the fruits ofMallotusphilippinensisrdquo Journal of Plant Biochemistry and Biotechnologyvol 20 no 2 pp 190ndash195 2011

[38] M S Akhtar and I Ahmad ldquoComparative efficacy of Mallotusphilippinensis fruit (Kamala) or Nilzan drug against gastroin-testinal cestodes in Beetal goatsrdquo Small Ruminant Research vol8 no 1-2 pp 121ndash128 1992

[39] A Jabbar M A Raza Z Iqbal and M N Khan ldquoAn inventoryof the ethnobotanicals used as anthelmintics in the southernPunjab (Pakistan)rdquo Journal of Ethnopharmacology vol 108 no1 pp 152ndash154 2006

[40] M Gangwar A Dalai A Chaudhary et al ldquoStudy on activityof alcoholic extract of glands and hairs of fruits of Mallotusphilippinensis in murine cestodal infection modelrdquo Interna-tional Journal of Pharmacy amp Pharmaceutical Sciences vol 4no 1 pp 643ndash645 2012

[41] M Gangwar V C Verma T D Singh S K Singh R KGoel and G Nath ldquoIn-vitro scolicidal activity of Mallotusphilippinensis (Lam) Muell Arg fruit glandular hair extractagainst hydatid cyst Echinococcus granulosusrdquo Asian PacificJournal of Tropical Medicine vol 6 no 8 pp 595ndash601 2013

[42] S S Gupta P Verma and K Hishikar ldquoPurgative andanthelmintic effects of Mallotus philippinensis in rats againsttape wormrdquo Indian Journal of Physiology amp Pharmacology vol28 no 1 pp 63ndash66 1984

[43] A Hussain M N Khan Z Iqbal and M S Sajid ldquoAn accountof the botanical anthelmintics used in traditional veterinarypractices in Sahiwal district of Punjab Pakistanrdquo Journal ofEthnopharmacology vol 119 no 1 pp 185ndash190 2008

[44] Q Hong D E Minter S G Franzblau M Arfan H Amin andM G Reinecke ldquoAnti-tuberculosis compounds from Mallotusphilippinensisrdquo Natural Product Communications vol 5 no 2pp 211ndash217 2010

[45] V K Gupta C Shukla G R S Bisht D Saikia S Kumarand R L Thakur ldquoDetection of anti-tuberculosis activity insome folklore plants by radiometric BACTEC assayrdquo Letters inApplied Microbiology vol 52 no 1 pp 33ndash40 2011

[46] R Tanaka T Nakata C Yamaguchi S Wada T Yamadaand H Tokuda ldquoPotential anti-tumor-promoting activity of3120572-Hydroxy-D a-friedooleanan-2-one from the stem bark ofMallotus philippinensisrdquo Planta Medica vol 74 no 4 pp 413ndash416 2008

[47] A Daikonya S Katsuki J B Wu and S Kitanaka ldquoAnti-allergic agents from natural sources (4) anti-allergic activityof new phloroglucinol derivatives from Mallotus philippinensis(Euphorbiaceae)rdquo Chemical and Pharmaceutical Bulletin vol50 no 12 pp 1566ndash1569 2002

[48] T K Chan S W David C Cheng S P Guan H MKoh and W S Wong ldquoAnti-allergic actions of rottlerin fromMallotus philippinensisis in experimental mast cell-mediatedanaphylactic modelsrdquo Phytomedicine vol 20 no 10 pp 853ndash860 2013

[49] M Khan R A Qureshi M Hussain K Mehmood and R AKhan ldquoHexane soluble extract ofMallotus philippinensis (Lam)Muell Arg root possesses anti-leukaemic activityrdquo ChemistryCentral Journal vol 7 no 1 article 157 2013

[50] R Roshan S G Kulkarni S P Tupe et al ldquoAntifungal dimericchalcone derivative kamalachalcone E from Mallotus philip-pinensisrdquo Natural Product Research Formerly Natural ProductLetters vol 28 no 4 pp 245ndash250 2014

[51] H Nakane M Arisawa A Fujita S Koshimura and KOno ldquoInhibition of HIV-reverse transcriptase activity by somephloroglucinol derivativesrdquo FEBS Letters vol 286 no 1-2 pp83ndash85 1991

[52] T Furumoto N Ozawa Y Inami et al ldquoMallotus philippinensisbark extracts promote preferential migration of mesenchymalstem cells and improve wound healing in micerdquo Phytomedicinevol 21 no 3 pp 247ndash253 2014

[53] Maeda ldquoMethod for producing Mallotus philippinensis dyecomposition and the compositionrdquo US7556829 B2 2009

[54] C Wiart Medicinal Plants of the Asia-Pacific Drugs for theFutureWorld Scientific Singapore 2006

[55] V R Sharma ldquoA review on endangered plant of Mallotusphilippinensis (Lam) MArgrdquo Pharmacologyonline vol 3 pp1256ndash1265 2011

[56] V Tangpu T Temjenmongla and A K Yadav ldquoAnticestodalproperty of Strobilanthes discolor an experimental study inHymenolepis diminutamdashratmodelrdquo Journal of Ethnopharmacol-ogy vol 105 no 3 pp 459ndash463 2006

[57] V Tangpu K Temjenmongla and A K Yadav ldquoAnticestodalactivity ofTrifolium repens extractrdquo Pharmaceutical Biology vol42 no 8 pp 656ndash658 2004

[58] A K Yadav and T Temjenmongla ldquoAnticestodal activity ofHouttuynia cordata leaf extract againstHymenolepis diminuta inexperimentally infected ratsrdquo Journal of Parasitic Diseases vol35 no 2 pp 190ndash194 2011

[59] T Temjenmongla and A K Yadav ldquoAnticestodal efficacy ofLasia spinosa extract against experimental Hymenolepis dimin-uta infections in ratsrdquo Pharmaceutical Biology vol 44 no 7 pp499ndash502 2006

BioMed Research International 13

[60] M L Dhar M M Dhar B N Dhawan B N Mehrotra and CRay ldquoScreening of Indian plants for biological activityrdquo IndianJournal of Experimental Biology vol 6 no 4 pp 232ndash247 1968

[61] Temjenmongla and A K Yadav ldquoAnticestodal efficacy offolklore medicinal plants of Naga tribes in north-east IndiardquoAfrican Journal of Traditional Complementary and AlternativeMedicines vol 2 pp 129ndash133 2005

[62] T V Tangpu and A K Yadav ldquoAnticestodal efficacy of Psidiumguajava against experimental Hymenolepis diminuta infectionin ratsrdquo Indian Journal of Pharmacology vol 38 no 1 pp 29ndash32 2006

[63] R Singh A Mehta P Mehta and K Shukla ldquoAnthelminticactivity of Rhizome extracts of Curcuma longa and Zingiberofficinalerdquo International Journal of Pharmacy and Pharmaceu-tical Sciences vol 3 no 2 pp 236ndash237 2011

[64] M K Asha D Prashanth B Murali R Padmaja and A AmitldquoAnthelmintic activity of essential oil of Ocimum sanctum andeugenolrdquo Fitoterapia vol 72 no 6 pp 669ndash670 2001

[65] J B Githiori J Hoglund P J Waller and R L Baker ldquoTheanthelmintic efficacy of the plantAlbizia anthelmintica againstthe nematode parasites Haemonchus contortus of sheep andHeligmosomoides polygyrus of micerdquo Veterinary Parasitologyvol 116 no 1 pp 23ndash34 2003

[66] N M Enwerema J I Okoguna C O Wambebea D A Oko-rieb and P A Akahc ldquoAnthelmintic activity of the stem barkextracts of Berlina grandiflora and one of its active principlesBetulinic acidrdquo Phytomedicine vol 8 pp 112ndash114 2001

[67] Z Iqbal M Lateef A Jabber M N Ghayur and A HGilani ldquoIn vitro and in vivo anthelmintic activity of Nicotianatabacum L leaves against gastrointestinal nematodes of sheeprdquoPhytotherapy Research vol 20 no 1 pp 46ndash48 2006

[68] Z Iqbal M Lateef A Jabbar G Muhammad and M N KhanldquoAnthelmintic activity of Calotropis procera (Ait) Ait F flowersin sheeprdquo Journal of Ethnopharmacology vol 102 no 2 pp 256ndash261 2005

Submit your manuscripts athttpwwwhindawicom

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MEDIATORSINFLAMMATION

of

Page 4: Mallotus philippinensis Muell. Arg (Euphorbiaceae ...

4 BioMed Research International

AcOH

H

H

CH3

CO2H

H3C

H3C

CH3 CH3

CH3

CH3

Figure 3 Acetylaleuritolic acid or aleuritic acid acetate

H

H

H

O

O

OH

CH3

CH3

CH3 CH3

CH3

CH3

H3C

H3C

H3C

Figure 4 3b-Acetoxy-22b-hydroxyolean-18-ene

of M Philippinensis [10] Apart from above triterpeniodsursane-type triterpenoid a-amyrin (Figure 5) reported fromthe petroleum ether and ethereal extracts ofM philippinensisbark [9]

33 Steroids Common steroid b-sitosterol (Figure 6) wasisolated from petroleum ether extracts of the heartwood andbark ofM philippinensis [9] Daucosterol was obtained fromether extract from bark ofM philippinensis [9]

34 Phenolic Compounds Isocoumarins Bergenin(Figure 7) an isocoumarin was isolated in 1972 fromthe heartwood ofM philippinensis This compound was alsoobtained from the bark and the leaves of M philippinensis[9]

Two new chalcone derivatives (flavonoids) kamalachal-cones A and B (Figures 8-9) with a unique ring systemcaused by dimerization between a dimethylchromene ringand a phenoxyl group were isolated from kamala (Mphilippinensis) [13] Three other novel chalcone derivativesmallotophilippens C D and E (Figures 10 11 12 13 and 14)were isolated from the fruits ofM philippinensis [14] lignanschalcones and dimeric chalcone derivatives [15]

Four phloroglucinol derivatives (kamalins) rottlerin andisorallorottlerin (Figures 15 and 16) were isolated from Mphilippinensis [16] Isorottlerin (Figure 17) was also men-tioned inM philippinensis [17]

Fruit and bark of plant contain condensed tanninsresponsible for antioxidant activity Methanolic bark extract

H

H

H

HO

CH3

CH3

CH3

CH3

CH3CH3

H3C

H3C

Figure 5 120572-Amyrin

H

H

H

H

OR

CH3

CH3

H3Ci-Pr

Et

Figure 6 120573-Sitosterol

OH

OHOH

OH

HO

MeO

O

O

O

Figure 7 Bergenin

O

O

O

O O

CH3

CH3

CH3

CH3

H3C

H3C

H

H

HHO

HO OH

Figure 8 Kamalachalcone A

BioMed Research International 5

O

O

O

O

O O

CH2

CH3

CH3

CH3

CH3

H3C

H3C

H3C

H

H

H

HO

HO

HO

HO OH

OH

Figure 9 Kamalachalcone B

O O

OOH

OHOH

HO HO 2

3

45

6

78

9

10

1112

1314

15

1998400

2998400

3998400

4998400

5998400

6998400

7998400

8998400

Figure 10 Mallotophilippen A or 1-[57-dihydroxy-22-dimethyl-6-(246-trihydroxy-3-isobutyryl-5-methyl-benzyl)-2H-chromen-8-yl]-2-methyl-butan-1-one

of M philippinensis subjected to characterization throughcolumn chromatography on a Sephadex LH-20 column usingethanol and acetone-water as the mobile phases tanninsand phenols were quantified Bark extract contains 541mggof total phenolics and infractions ranging from 54mgg(fraction I) to 927mgg (fraction VI) and condensed tanninswere detected in fractions IIndashVI [18 19] In 1989 leaves ofM philippinensis were reported for tannins and other relatedcompounds by Saijo et al [20]

35 Other Compounds Unsaturated fatty acids that is triply-unsatured hydroxy acid kamlolenic acid different fatty acidsand glyceride [21] have been reported from Kamala (Mphilippinensis) seed oil

Resinous coloured material contains active parts of rott-lerin and isorottlerin It also contains homorottlerine red role50 yellow role 5 manure 2 volatile oils tannin gumcitric acid and oxalic acid

4 Pharmacological Activities

41 Antifilarial Activity The effect of aqueous and alcoholicleave extracts of M philippinensis (Lam) Muell was studiedon the spontaneous movements of the whole worm and

O O

OOH

OHOH

HO HO 2

3

45

6

78

9

10

1112

1314

15

1998400

2998400

3998400

4998400

5998400

6998400

7998400

Figure 11 Mallotophilippen B or 1-[6-(3-acetyl-246-trihydroxy-5-methyl-benzyl)-57-dihydroxy-22-dimethyl-2H-chromen-8-yl]-2-methyl-butan-1-one

OH

OH

HO

OHO

Figure 12 Mallotophilippen C or (1-[6-(37-dimethyl-octa-26-dienyl)-57-dihydroxy-22-dimoethyl-2H-chromen-8-yl]-3-(4-hy-droxy-phenyl)-propenone) R = H

OH

OH

OHO

OHO

Figure 13 Mallotophilippen D or 3-(34-dihydroxy-phenyl)-1-[6-(37-dimethyl-octa-26-dienyl)-57-dihydroxy-22-dimethyl-2H-chromen-8-yl]-propenone R = OH

nerve-muscle (nm) preparation of Setaria cervi and on thesurvival of microfilariae in vitro Both the extracts result ininhibition of spontaneous motility of whole worm and thenm preparation of S cervi characterized by initial stimula-tion followed by depression in amplitude The tone and rateof contractions remained visibly unaffected Aqueous extractat higher concentration showed immediate reduction in toneThe concentration required to inhibit the movements of nmpreparation was 15th for aqueous and 111th for alcoholicextract compared to that for the whole worm suggesting acuticular permeability barrier The stimulatory response ofacetylcholine was blocked by aqueous extract onwhole worm

6 BioMed Research International

OH

OH

OH

O

OHO

Figure 14 Mallotophilippen E or 1-[57-dihydroxy-2-methyl-6-(3-methyl-but-2-enyl)-2-(4-methyl-pent-3-enyl)-2H-chromen-8-yl]-3-(34-dihydroxy-phenyl)-propenone

OH

OH

OHOH

O

O

O

HO

Figure 15 Rottlerin

movements On the microfilariae the LC50and LC

90were 18

and 20 ngmL for aqueous and 12 and 15 ngmL for alcoholicextracts respectively [2] Further study will be required toevaluate the same activity with its phytochemicals

42 Antifertility Activity Seeds extract of M philippinensisexhibits adverse effects on different reproductive parametersof female rats According to the study extract reducesserum FSH and LH levels probably by affecting hypotha-lamicpituitary axis in experimental animals This reducedlevel may affect follicular development quality of ovulatedeggs corpus luteum formation estrus cycle andmaintenanceof pregnancy in rats [22] This antifertility effect of plantextract is supposed to be caused by rottlerin (Figure 15) aphloroglucinol derivative Acetyl rottlerin may be active butisorottlerin (Figure 17) is either inactive or slightly active [23]Effect of pure rottlerin can be further studied so as to clarifythe potential of phloroglucinol derivatives

43 Antibacterial and Antifungal Activity A series of 61Indian medicinal plants belonging to 33 different familiesused in various infectious disorders were screened for theirantimicrobial properties Screening was carried out at 1000and 500 120583gmL concentrations by agar dilution methodagainst Bacillus cereus varmycoides Bacillus pumilus Bacillussubtilis Bordetella bronchisepticaMicrococcus Luteus Staphy-lococcus aureus Staphylococcus epidermidis Escherichia coli

OH

OH

O

O

O

HO

HO

HO

Figure 16 Isoallorottlerin

OH

OH

O

O

O

OHO

HO

Figure 17 Isorottlerin

Klebsiella pneumonia Candida albicans and Saccharomycescerevisiae Twenty-eight plant extracts showed activity againstat least one of the test organisms used in the screeningOn the basis of the results obtained study concludes thatthe crude extracts of M philippinensis exhibited significantantimicrobial activity [3] and properties that support folk-loric use in the treatment of some diseases as broad-spectrumantimicrobial agents Steam bark of plant and its chloroformfractions and the methanolic extract significantly inhibitthe pathogenic bacteria with significant zones of inhibitioncomparable to the standard drug used However the hexanicextract did not show any significant activity [24] Glandularhair of fruits of Mallotus exhibits significant antibacterialactivity against human pathogenic bacteria withMIC ranging15ndash20mgmL This extract does not show any inhibitionagainst different species of candida This shows that fruitextract possesses antibacterial activity without any antifungalpotential The results of the study may justify the use of theplant against bacterial pathogens This probably explains theuse of these plants by the indigenous people against a numberof infections [25]

However ethanolic extract shows potent anti-Heli-cobacter pylori activity at the concentration of 156ndash312mgLagainst eight H pylori strains Further purification of extractrevealed that rottlerin exhibits potent bactericidal effectwith minimal bactericidal concentration (MBC) of 312ndash625mgL against different resistant strains of clarithromycin

BioMed Research International 7

M philippinensis

Rottlerin

Fruit

H3C

HO

HO

OH OH

OH

O

O

O

CH3

CH3

CH3

Antifertility

Antimicrobial

Protein inhibition

Antituberculosis activity

Antiallergic activity

Antiproliferative activity

Antiparasitic (cestodal)

Figure 18 Rottlerin and its major biological activities

and metronidazole including Japanese and Pakistani strains[17]

44 Anti-Inflammatory and Immunoregulatory ActivityChalcones derivatives from the fruits of M philippinensisand mallotophilippens C D and E (Figures 12 13 and14) inhibit nitric oxide (NO) production and inducibleNO synthase (iNOS) gene expression by a murinemacrophage-like cell line (RAW 2647) which was activatedby lipopolysaccharide (LPS) and recombinant mouseinterferon-gamma (IFN-gamma) Further investigationssuggest the downregulation of cyclooxygenase-2 geneinterleukin-6 gene and interleukin-1b gene expressionThe above results show that these chalcones have goodanti-inflammatory and immunoregulatory effects [26]

45 Antioxidant Activity and Antiradical Activity Differentfractions of bark and fruit of Mallotus were studied forits total antioxidant activity (TAA) and antiradical activityagainst DPPH on a Sephadex LH-20 column using ethanoland acetone-water asmobile phase Among different extractsbark fraction showed the strongest antiradical activity (TAAvaluemdash527 mmol Trolox equivg) and reducing powerAnother extract that is phenolic fraction shows TAAranging from 058mmol Troloxg (fraction I) to 682mmolTroloxg (fraction IV) this is the strongest fraction showingantiradical activity against DPPH and reducing power TAAof other extracts ranged from 005 to 179mmol Troloxequivg [18 19]

46 Protein Inhibition Implicated in Cancer Processes Proteinkinase is inhibited with some specificity for PKC by rottlerina compound isolated from Mallotus Inhibition of PKCappears due to a strong competition between rottlerin andATP CaM-kinase III is suppressed by rottlerin as effectivelyas PKC 120575 among different protein kinases tested Novelinhibition property and improved selectivity for a distinctPKC isoenzyme of rottlerin are suggestive from its chemicalstructure [27 28] Rottlerin is also very potent in blockingother kinases including AktPKB and p38 MAPK [29ndash31] Italso inhibits human T cell responses [32] reduces MUC5ACexpression in human epithelial cells [33] abrogates reactiveoxygen species production in hepatic stellate cells [34] andprevents histamine-induced H1-receptor gene expression inHeLa cells [35] However still very limited information isavailable of rottlerin towards cancer disease and its mecha-nism of action

47 Hepatoprotective Activity Methanolic extract of Mphilippinensis leaves decreases the CCl

4-induced elevation in

biochemical parameters (SGOT SGPT SALP direct biliru-bin total bilirubin andMDA) on pretreatment at doses 100ndash200mgkg and also reversed the functional and antioxidantparameters This study suggests that leave extract was effec-tive in functional improvement of hepatocytes Histopatho-logical studies also suggest the hepatoprotective activity ofplant [36]

48 In Vitro Cytotoxicity against Human Cancel Cell Glan-dular hair extract of Mallotus fruit powder was assayed

8 BioMed Research International

(a) (b)

(c) (d)

(e)

Figure 19 Mallotus philippinensis (a) Mature plant (b) leaf (c) initial inflorescence of seed setting (d) mature fruits twig (e) mature fruitwith seed

against 14 human cancer cell lines among different fractions95 ethanolic extract showed the highest cytotoxic effect ascompared to 50 ethanolic and aqueous portion Furtherthe chromatographic analysis of the said fraction afforded apolyphenolic molecule rottlerin inMallotus plant [37]

49 Anticestodal ActivityVeterinary Applications M philip-pinensis fruit was found to be very effective against gas-trointestinal cestodes in Beetal goats and other ruminantsComparative anticestodal efficacies of single oral dose treat-ments with the powdered fruit ofM philippinensis (125 250and 375mgkg) its water or methanol extracts (equivalent to375mgkg) and the total glycosides (25 50 and 100mgkg)were determined in naturally cestode-infected Beetal goats[38] An ethnobotanical survey has been conducted foranthelmintics in ruminants so as to document the plantsused to treat and control helminthes Mallotus has beenfrequently used to treat helminthosis in ruminants [39] M

philippinensis fruit extract of 800mgkg twice daily for 3days was observed to have curative efficacy against matureadult worms of Hymenolepis diminuta The total follow-upperiod of 90 days did not show any further excretion of eggsin the faeces of treated rats Praziquantel at the dosage of5mgkg also produced a similar effect [40] In vitro scolicidalactivity ofM philippinensis (Lam)Muell Arg fruit glandularhair extract against hydatid cyst Echinococcus granulosusprotoscoleces at concentrations 10 and 20mgmL shows themortality rate 97 to 99 respectively for 60min treatmentwhile up to 93 mortality was observed with 20mgmLfor only 10min treatment This proves that the extract hassignificant scolicidal activity with almost no associated sideeffects [41] In vivo animal model experiment will be furtherrequired to prove its effect against Hydatid cyst

410 Purgative Activity and Anthelmintic Activity A signifi-cant purgative effect after an oral dose (120mgkg) in rats was

BioMed Research International 9

assessed from resins isolated from plant Its effect was evalu-ated from the weight of faeces as well as from surface areaof blotting paper soaked by liquid faeces The anthelminticeffect on tape worm was evaluated in albino rates fromthe resin of the plant showed lethal effect of 3569 and7821 respectively in small intestine in concentrations 60and 120mgkg respectively [42 43]

411 Antituberculosis Activity Organic extract of plant afterbioassay-directed fractionation yields five compounds themost active of which againstMycobacterium tuberculosis wasa new compound 8-cinnamoyl-57-dihydroxy-22-dimethyl-6-geranylchromene for which the name mallotophilippenF is suggested The second compound 8-cinnamoyl-22-dimethyl-7-hydroxy-5-methoxychromene was isolated froma natural source for the first time while the remaining threecompounds rottlerin isoallorottlerin or isorottlerin andthe so-called ldquored compoundrdquo 8-cinnamoyl-57-dihydroxy-226-trimethylchromene had been already isolated fromthis plant Isolated compounds were identified by 2D-NMRand C-13 NMR [44] Ethanolic extract of plant was assayedfor antimycobacterial activity against M smegmatis by discdiffusion assay Further antituberculosis potential of leavesextract was identified by radiometric BACTEC assay resultrevealed that ethanolic extract ofM philippensis showed anti-tuberculosis activity against virulent and avirulent strains ofM tuberculosis H37Rv andM tuberculosis H37Ra with min-imum inhibitory concentrations of 025 and 0125mgmLminus1respectively The inhibition in growth index values of Mtuberculosis was observed in the presence of ethyl acetatefraction at a minimum concentration of 005mgmLminus1 Itsuggests that ethanolic and ethyl acetate fraction of plantpossesses significant antimycobacterial activity [45] Steambark of M philippinensis has also been reported for itsantitumor promoting effect which was due to the presenceof 3120572-Hydroxy-DA-friedooleanan-2-one [46]

412 Antiallergic Activity M philippinensis fruit containstwo new phloroglucinol derivatives mallotophilippensA and B (Figures 10 and 11) which were identified usingchemical and spectral data as 1-[57-dihydroxy-22-di-methyl-6-(246-trihydroxy-3-isobutyryl-5-methyl-benzyl)-2H-chromen-8-yl]-2-methyl-butan-1-one and 1-[6-(3-Acetyl-246-trihydroxy-5-methyl-benzyl)-57-dihydroxy-22-dim-ethyl-2H-chromen-8-yl]-2-methyl-butan-1-one respe-ctively These compounds inhibited the production ofnitric oxide (NO) and inducible NO synthase (iNOS) geneexpression by a murine macrophage-like cell line (RAW2647) which was activated by lipopolysaccharide (LPS)and recombinant mouse interferon-g (IFN-g) Furtherphloroglucinol derivatives inhibit histamine release from ratperitoneal mast cells induced by compound 4880This studysuggests its anti-inflammatory activity [47] Rottlerin hasbeen tested in animal models of IgE-dependent anaphylaxisand the antiallergic mechanisms of action in mast cellsAntiallergic action of rottlerin has been tested in passivecutaneous anaphylaxis and passive systemic anaphylaxismouse models and in anaphylactic contraction of bronchial

rings isolated from sensitized guinea pigs This experimentsproves antiallergic effect of rottlerin by blocking IgE-inducedmast cell degranulation This report suggests the use ofrottlerin in mast cell-mediated allergic disorders includingurticaria and allergic asthma [48]

413 Anti-Leukaemic Activity Root extract ofM philippinen-sis was tested on human promyelocytic leukemia HL-60 cellproliferation cell cycle regulators and apoptosis in order toinvestigate its antileukemic effect Hexane fraction showedpromising toxicity against p53-deficient HL-60 cells (IC

50

15mg dry roots equivalentmL medium) after 72 h andinterestingly inhibition of cell proliferation was preceded bythe upregulation of the protooncogenes Cdc25A and cyclinD1 within 24 hours suggesting its antileukemic effect inHL-60 cells After isolation and identification by GC-MSpolyphenols were the main compounds of the hexane extractthat inhibited proliferation and induced apoptosis [49]

414 Antiproliferative Activity Antiproliferative effect wasevaluated against Thp-1 cell lines from the isolated com-pounds of M philippinensis fruit extract in which 41015840-hydroxyrottlerin showed 54 growth inhibition ofThp-1 cellline [50] Other isolated compounds were also tested againstdifferent fungi andwere found to be very effective IC

50values

415 Anti-HIV Activity Four phloroglucinol derivativesnamed mallotophenone (5-methylene-bis-26-dihydroxy-3-methyl-4-methoxyacetophenone) mallotochromene (8-acetyl-57-dihydroxy-6-(3-acetyl-24-dihydroxy-5-methyl-6-methoxybenzyl)-22-dimethylchromene) mallotojaponin(3-(33(dimethylallyl) S-(3(acetyl-24-dihydroxy-5-methyl-6-methoxybenzyl)-phloracetophenone) andmallotolerin (3-(3-methyl-2-hydroxybut-3-enyl)-5-(3-acetyl-24-dihydroxy-5-methyl-6-methoxybenzyl)-phloracetophenone) weretested for their ability to inhibit the activity of humanimmunodeficiency virus- (HIV-) reverse transcriptaseThe mode of inhibition of mallotojaponin was foundto be competitive with respect to the template primer(rA)n (dT)12ndash18 and noncompetitive with respect to thetriphosphate substrate dTTPThe Ki value of mallotojaponinfor HIV-reverse transcriptase was determined to be 61 120583M[51]

416 Antitumor Activity Four known friedelane-type trit-erpenoids friedelin 3-hydroxy-DA-friedoolean-3-en-2-one 2120573-hydroxy-DA-friedooleanan-3-one and 3120572-hy-droxy-DA-friedooleanan-2-one and two known lupane-type triterpenoids lupeol and betulin were isolated fromthe stem bark of M philippinensis and were tested fortheir inhibitory effects on Epstein-Barr virus early antigen(EBV-EA) activation induced by 12-O-tetradecanoylphorbol13-acetate (TPA) The inhibitory effect of compounds 2(IC50

= 292mol ratio32 pmolTPA) and 4 (IC50

= 288) wasstronger than those of the other compounds tested and thepositive control curcumin (IC

50= 343) Compound 3120572-

hydroxy-DA-friedooleanan-2-one strongly inhibited mouse

10 BioMed Research International

skin tumor promotion in an in vivo two-stage carcinogenesismodel [46]

417 Wound Healing and Mesenchymal Stem Cell (MSC)Proliferation Bark extract ofMallotus philippinensis has beentested in vitro for wound healing activity by examining theproliferation and migration of MSCs KUM6 cells prolifer-ation and migration have been enhanced at 016ndash4 120583gmLand unregulated the activity of MSCs by secreting variouscytokines to wounded site from bone marrow to systemiccirculation and finally remodel wounded tissues [52]

418 Toxicities Seeds of M philippinensis ethereal extracthave adverse effect on various parameters of female rats Eventhe extract reduces serum levels of gonadotropins in treatedanimals at high dose of 100mgkg body weight Reducedweights of ovary and uterus follicular development andincreased atretic follicular in the ovary are due to subnormallevels of steroid hormones Thus pregnancy is very difficultin female rats treated with kamala seed extract [22]

419 Colouring Agent-Dye Glandular hairs of fruit aremostly used as an orange dye for silk [53 54]

5 Pharmacognostic Evaluation ofMallotus philippinensis

Morphological study shows that fruit depresses globoseand is three-lobed capsule 5ndash7mm times 8ndash10ndash12mm stellate-puberulose and with abundant orange or reddish glan-dular granules Seeds are subglobose and black in colorOrganoleptic property of the red fruit shows that it is tastelessand odourless Microscopic description showed the presenceof epicarp which contained a compactly packed layer ofmucilaginous cells and mesocarp composed of columnarcells which are closely arranged Its polygonal cells are com-pactly arranged in 2-3 layers Presence of lignified vasculararrangement has been observed in the transverse section [55]

6 Conclusion and Future Perspective

Medicinal plants have been clinically used and its interest hasbeen dramatically increased over the past decades throughoutthe world and its formulations are increasingly cited inmedia Daily consumption of the natural products and theirformulations by an extensive number of patients lead toserious concern for scientist to study its efficacy and safetyBecause of extensive use and its benefits natural productsin many countries are regulated both as medicinal productsand as food supplements often labeled as natural foodsupplements

Traditional use and its growing demand for Mallotusphilippinensis and its other species lead to compile this reviewand commented on the current knowledge provided byclinical and preclinical research on the effect of this plant

Mallotus philippinensis has been widely used as tradi-tional medicine in several parts of countries including IndiaEvery part of this plant possesses its specific medicinal prop-erties and is usedmainly in ayurveda to fight against intestinalworms in domestic and grazing animals when administeredwith jaggeryHowever only a few reports are attributed to thisplant and its different parts and there is a large scope for inves-tigation Hence it is required to explore more of its potentialwithin the field of medicinal and pharmaceutical sciences fornovel and fruitful application of this plant in form of naturalformulation Along with this medicinal importance thisplant is used against human pathogens including H pylorianti-inflammatory activity antioxidant antiradical proteininhibition hepatoprotective antiallergic anti-HIV activityand many more Phytochemical investigation revealed that alarge number phenol derivatives and several miscellaneouscompounds from different classes have been isolated fromthis species The phenols diterpenoids steroids flavonoidscardenolides triterpenoids coumarins and isocoumarinsare mostly distributed in all parts of the plant The othermajor isolated pure compounds from this species mostlybelong to phenolic group exhibiting most of the biologicalactivity Various types of extracts from different parts andsingle compounds derived from this species have beenfound to possess biological activities including antioxidantantimicrobial anti-inflammatory cytotoxicity and immunemodulatory Fruit and bark of plant contain condensed tan-nins responsible for antioxidant activity Somenovel chalconederivatives mallotophilippens C D and E were isolatedfrom the fruits of M philippinensis Mallotoxin or rottlerinhas great anticancerous potential Among the ever-anticanceragents rottlerin appears to have great potentiality for beingused in chemotherapy Rottlerin will become a potentialmolecule for research in future to treat cancerous cell as itwill affect cell machineries involved in apoptosis survivaland autophage This suggests the view that this species haspotential to be a beneficial chemotherapeutic remedy

Although the data and other reports provided that thismedicinal plant is of great biological use in different phar-macological activities including anticancer further researchis needed in different areas regarding the toxicity and efficacyof pure phytochemicals isolated from different parts of thisplant More data will be needed from preclinical and clinicalstudies on humans to clarify its potency and safety aslack of knowledge with respect to its adverse effects andmethodological accuracy in the literature limits towardsits standardized formulation Furthermore the mechanismof action of the phytochemicals and extract of Mallotusphilippinensis is unclear more exhaustive studies will beperformed to explore its mechanism and structure activityrelationship among various constituents

In conclusion this review confirms the great potential ofMallotus philippinensis As very limited information is stillknown for this species it leads us to continue the study ondifferent species of Mallotus plant and its interesting phar-macological properties Further natural product chemistryof isolated moiety and its structural analysis of compounds

BioMed Research International 11

responsible for these activities will be an interesting field ofresearch

Conflict of Interests

The authors declare that there is no conflict of interests re-garding the publication of this paper

Acknowledgment

The authors gratefully acknowledge the financial supportprovided by CSIR Government of India New Delhi forawarding SRF in the form of research fellowship

References

[1] C-J Widen and H S Puri ldquoNatural occurrence and chemicalvariability of phloroglucinols inKamalardquoPlantaMedica vol 40no 3 pp 284ndash287 1980

[2] R Singh K C Singhal and N U Khan ldquoAntifilarial activity ofMallotus philippinensisLam on Setaria cervie (Nematoda Filar-ioidea) in-vitrordquo Indian Journal of Physiology andPharmacologyvol 41 no 4 pp 397ndash403 1997

[3] V P Kumar N S Chauhan H Padh and M Rajani ldquoSearchfor antibacterial and antifungal agents from selected Indianmedicinal plantsrdquo Journal of Ethnopharmacology vol 107 no2 pp 182ndash188 2006

[4] S Shrikumar and T K Ravi ldquoApproaches towards developmentand promotion of herbal drugsrdquo Pharmaceutical Reviews vol 1no 1 pp 180ndash183 2007

[5] C Orwa A Mutua and R Kindt ldquoAgroforestree Database atree reference and selection guiderdquo Version 4 0 2009

[6] K Usmanghani A Saeed and M T Alam ldquoIndusynicMedicine Karachirdquo Research Institute of Indusyunic Medicinevol 1997 pp 285ndash287 1997

[7] F Ahmad and S Hashmi ldquoAdulteration in commercial Kamila(Mallotus philippinensisMuell) an anthelmintic drug of reputerdquoHamdard Medicus vol 38 pp 62ndash67 1995

[8] K D Roberts E Weiss and T Reichstein ldquoGlycosides andaglycons CCLII Cardenolides of the seed of Mallotus philip-pinensisrdquo Helvetica Chimica Acta vol 46 pp 2886ndash2893 1963

[9] M Bandopadhyay V K Dhingra and S K Mukerjee ldquoTriter-penoid and other components of Mallotus philippinensisrdquo Phy-tochemistry vol 11 no 4 p 1511 1972

[10] S P Nair and J Madhusudana Rao ldquoKamaladiol-3-acetate fromthe stem bark of Mallotus philippinensisrdquo Phytochemistry vol32 pp 407ndash409 1993

[11] J DWansi JWandjiW A Kamdem et al ldquoTriterpenoids fromDrypetes chevalieri Beille (Euphorbiaceae)rdquo Natural ProductResearch vol 20 no 6 pp 586ndash592 2006

[12] P Castenada A Bahena and E Garcia ldquoChemical studieson Mexican plants used in traditional medicine XXIX Sec-ondary metabolites from the stem bark of Celaeno-dendronmexicanumrdquo Journal of Natural Products vol 56 pp 1575ndash15791993

[13] T Tanaka T Ito M Iinuma Y Takahashi and H NaganawaldquoDimeric chalcone derivatives from Mallotus philippinensisrdquoPhytochemistry vol 48 no 8 pp 1423ndash1427 1998

[14] T M Nguyen V M Chau V K Phan et al ldquoStudy on chemicalconstituents of the leaves of Mallotus philippinensisrdquo Tap ChiHoa Hoc vol 48 pp 352ndash357 2010

[15] M Furusawa Y Ido T Tanaka et al ldquoNovel complex flavonoidsfrom Mallotus philippinensis (Kamala tree)rdquo Helvetica ChimicaActa vol 88 no 5 pp 1048ndash1058 2005

[16] M Lounasmaa C J Widen C M Tuuf and A HuhtikangasldquoOn the phloroglucinol derivatives of Mallotus philippinensisrdquoPlanta Medica vol 28 no 1 pp 16ndash31 1975

[17] S F H Zaidi I Yoshida F Butt et al ldquoPotent bactericidal con-stituents from Mallotus philippinensis against clarithromycinand metronidazole resistant strains of Japanese and Pakistanihelicobacter pylorirdquo Biological and Pharmaceutical Bulletin vol32 no 4 pp 631ndash636 2009

[18] M Arfan H Amin M Karamac et al ldquoAntioxidant activityof extracts of Mallotus philippinensis fruit and barkrdquo Journal ofFood Lipids vol 14 no 3 pp 280ndash297 2007

[19] M Arfan K Hazrat and K Magdalena ldquoAntioxidant activityof phenolic fractions of Mallotus philippinensis bark extractrdquoJournal of Food Science vol 27 no 2 pp 109ndash117 2009

[20] R Saijo G Nonaka and I Nishioka ldquoTannins and related com-pounds LXXXVIII Isolation and characterization of hydrolyz-able tannins fromMallotus japonicus (Thunb)Mueller-Arg andM philippinensis (Lam)Mueller-ArgrdquoChemical amp Pharmaceu-tical Bulletin vol 37 no 11 pp 2940ndash2947 1989

[21] S C Gupta S S Gupta and J S Aggarwal ldquoChemical exami-nation of the seeds of Mallotus philippinensis III Constitutionof kamlolenic acid isolated from the oilrdquo Journal of Scientific ampIndustrial Research vol 12 pp 240ndash242 1953

[22] S C Thakur S S Thakur S K Chaube and S P Singh ldquoAnetheral extract of Kamala (Mallotus philippinensis (Moll Arg)Lam) seed induce adverse effects on reproductive parametersof female ratsrdquo Reproductive Toxicology vol 20 no 1 pp 149ndash156 2005

[23] M L Gujral D R Varma K N Sareen and A K Roy ldquoOralcontraceptives II Antifertility effect ofMallotus philippinensisrdquoIndian Journal of Medical Research vol 48 pp 52ndash58 1960

[24] KMoorthy K Srinivasan C Subramanian CMohanasundariand M Palaniswamy ldquoPhyto-chemical screening and antibac-terial evaluation of stem bark of Mallotus philippinensis varTomentosusrdquoAfrican Journal of Biotechnology vol 6 no 13 pp1521ndash1523 2007

[25] M Gangwar D Kumar R Tilak et al ldquoQualitative phy-tochemical characterization and antibacterial evaluation ofglandular hairs ofMallotus philippinensis fruit extractrdquo Journalof Pharmacy Research vol 4 no 11 pp 4214ndash4216 2011

[26] A Daikonya S Katsuki and S Kitanaka ldquoAntiallergic agentsfrom naturalsources 9 Inhibition of nitric oxide productionby novel chalcone derivatives from Mallotus philippinensis(Euphorbiaceae)rdquo Chemical amp Pharmaceutical Bulletin vol 52no 11 pp 1326ndash1329 2004

[27] M Gschwendt H J Muller K Kielbassa et al ldquoRottlerina novel protein kinase inhibitorrdquo Biochemical and BiophysicalResearch Communications vol 199 no 1 pp 93ndash98 1994

[28] Y F Liao Y C Hung W H Chang et al ldquoThe PKC deltainhibitor rottlerin induces apoptosis of haematopoietic celllines through mitochondrial membrane depolarization andcaspasescascaderdquo Life Sciences vol 77 no 6 pp 707ndash719 2005

[29] H S Kang E K Park K H Kim et al ldquoReceptor activatorof nuclear factor-kappa B is induced by a rottlerin-sensitiveand p38 MAP kinase-dependent pathway during monocytedifferentiationrdquoMolecules and Cells vol 17 no 3 pp 438ndash4452004

12 BioMed Research International

[30] S P Soltoff ldquoRottlerin an inappropriate and ineffectiveinhibitor of PKC120575rdquo Trends in Pharmacological Sciences vol 28no 9 pp 453ndash458 2007

[31] Y Choi D K Kim S S Kang J K Sonn and E J Jin ldquoIntegrinsignaling and cell spreading alterations by rottlerin treatment ofchick limb bud mesenchymal cellsrdquo Biochimie vol 91 no 5 pp624ndash631 2009

[32] C Springael S Thomas S Rahmouni et al ldquoRottlerin inhibitshuman T cell responsesrdquo Biochemical Pharmacology vol 73 no4 pp 515ndash525 2007

[33] J H Choi Y P Hwang E H Han et al ldquoInhibition of acrolein-stimulated MUC5AC expression by Platycodon grandiflorumroot-derived saponin in A549 cellsrdquo Food and Chemical Toxi-cology vol 49 no 9 pp 2157ndash2166 2011

[34] E L M Guimaraes C Empsen A Geerts and L A vanGrunsven ldquoAdvanced glycation end products induce produc-tion of reactive oxygen species via the activation of NADPHoxidase in murine hepatic stellate cellsrdquo Journal of Hepatologyvol 52 no 3 pp 389ndash397 2010

[35] H Mizuguchi T Terao M Kitai et al ldquoInvolvement of pro-tein kinase C120575extracellular signal-regulated kinasepoly(ADP-ribose) polymerase-1 (PARP-1) signaling pathway in histamine-induced up-regulation of histamine H1 receptor gene expres-sion in HeLa cellsrdquo Journal of Biological Chemistry vol 286 no35 pp 30542ndash30551 2011

[36] S Ramakrishna K M Geetha P V V S Bhaskar gopalR P Kumar C P Madav and L Umachandar ldquoEffect ofMallotus PhilippinensisMuell-Arg leaves against hepatotoxicityof Carbon tetrachloride in ratsrdquo International Journal of Phar-maceutical Sciences and Research vol 2 pp 74ndash83 2011

[37] V Sharma ldquoA polyphenolic compound rottlerin demonstratessignificant in vitro cytotoxicity against human cancer celllines isolation and characterization from the fruits ofMallotusphilippinensisrdquo Journal of Plant Biochemistry and Biotechnologyvol 20 no 2 pp 190ndash195 2011

[38] M S Akhtar and I Ahmad ldquoComparative efficacy of Mallotusphilippinensis fruit (Kamala) or Nilzan drug against gastroin-testinal cestodes in Beetal goatsrdquo Small Ruminant Research vol8 no 1-2 pp 121ndash128 1992

[39] A Jabbar M A Raza Z Iqbal and M N Khan ldquoAn inventoryof the ethnobotanicals used as anthelmintics in the southernPunjab (Pakistan)rdquo Journal of Ethnopharmacology vol 108 no1 pp 152ndash154 2006

[40] M Gangwar A Dalai A Chaudhary et al ldquoStudy on activityof alcoholic extract of glands and hairs of fruits of Mallotusphilippinensis in murine cestodal infection modelrdquo Interna-tional Journal of Pharmacy amp Pharmaceutical Sciences vol 4no 1 pp 643ndash645 2012

[41] M Gangwar V C Verma T D Singh S K Singh R KGoel and G Nath ldquoIn-vitro scolicidal activity of Mallotusphilippinensis (Lam) Muell Arg fruit glandular hair extractagainst hydatid cyst Echinococcus granulosusrdquo Asian PacificJournal of Tropical Medicine vol 6 no 8 pp 595ndash601 2013

[42] S S Gupta P Verma and K Hishikar ldquoPurgative andanthelmintic effects of Mallotus philippinensis in rats againsttape wormrdquo Indian Journal of Physiology amp Pharmacology vol28 no 1 pp 63ndash66 1984

[43] A Hussain M N Khan Z Iqbal and M S Sajid ldquoAn accountof the botanical anthelmintics used in traditional veterinarypractices in Sahiwal district of Punjab Pakistanrdquo Journal ofEthnopharmacology vol 119 no 1 pp 185ndash190 2008

[44] Q Hong D E Minter S G Franzblau M Arfan H Amin andM G Reinecke ldquoAnti-tuberculosis compounds from Mallotusphilippinensisrdquo Natural Product Communications vol 5 no 2pp 211ndash217 2010

[45] V K Gupta C Shukla G R S Bisht D Saikia S Kumarand R L Thakur ldquoDetection of anti-tuberculosis activity insome folklore plants by radiometric BACTEC assayrdquo Letters inApplied Microbiology vol 52 no 1 pp 33ndash40 2011

[46] R Tanaka T Nakata C Yamaguchi S Wada T Yamadaand H Tokuda ldquoPotential anti-tumor-promoting activity of3120572-Hydroxy-D a-friedooleanan-2-one from the stem bark ofMallotus philippinensisrdquo Planta Medica vol 74 no 4 pp 413ndash416 2008

[47] A Daikonya S Katsuki J B Wu and S Kitanaka ldquoAnti-allergic agents from natural sources (4) anti-allergic activityof new phloroglucinol derivatives from Mallotus philippinensis(Euphorbiaceae)rdquo Chemical and Pharmaceutical Bulletin vol50 no 12 pp 1566ndash1569 2002

[48] T K Chan S W David C Cheng S P Guan H MKoh and W S Wong ldquoAnti-allergic actions of rottlerin fromMallotus philippinensisis in experimental mast cell-mediatedanaphylactic modelsrdquo Phytomedicine vol 20 no 10 pp 853ndash860 2013

[49] M Khan R A Qureshi M Hussain K Mehmood and R AKhan ldquoHexane soluble extract ofMallotus philippinensis (Lam)Muell Arg root possesses anti-leukaemic activityrdquo ChemistryCentral Journal vol 7 no 1 article 157 2013

[50] R Roshan S G Kulkarni S P Tupe et al ldquoAntifungal dimericchalcone derivative kamalachalcone E from Mallotus philip-pinensisrdquo Natural Product Research Formerly Natural ProductLetters vol 28 no 4 pp 245ndash250 2014

[51] H Nakane M Arisawa A Fujita S Koshimura and KOno ldquoInhibition of HIV-reverse transcriptase activity by somephloroglucinol derivativesrdquo FEBS Letters vol 286 no 1-2 pp83ndash85 1991

[52] T Furumoto N Ozawa Y Inami et al ldquoMallotus philippinensisbark extracts promote preferential migration of mesenchymalstem cells and improve wound healing in micerdquo Phytomedicinevol 21 no 3 pp 247ndash253 2014

[53] Maeda ldquoMethod for producing Mallotus philippinensis dyecomposition and the compositionrdquo US7556829 B2 2009

[54] C Wiart Medicinal Plants of the Asia-Pacific Drugs for theFutureWorld Scientific Singapore 2006

[55] V R Sharma ldquoA review on endangered plant of Mallotusphilippinensis (Lam) MArgrdquo Pharmacologyonline vol 3 pp1256ndash1265 2011

[56] V Tangpu T Temjenmongla and A K Yadav ldquoAnticestodalproperty of Strobilanthes discolor an experimental study inHymenolepis diminutamdashratmodelrdquo Journal of Ethnopharmacol-ogy vol 105 no 3 pp 459ndash463 2006

[57] V Tangpu K Temjenmongla and A K Yadav ldquoAnticestodalactivity ofTrifolium repens extractrdquo Pharmaceutical Biology vol42 no 8 pp 656ndash658 2004

[58] A K Yadav and T Temjenmongla ldquoAnticestodal activity ofHouttuynia cordata leaf extract againstHymenolepis diminuta inexperimentally infected ratsrdquo Journal of Parasitic Diseases vol35 no 2 pp 190ndash194 2011

[59] T Temjenmongla and A K Yadav ldquoAnticestodal efficacy ofLasia spinosa extract against experimental Hymenolepis dimin-uta infections in ratsrdquo Pharmaceutical Biology vol 44 no 7 pp499ndash502 2006

BioMed Research International 13

[60] M L Dhar M M Dhar B N Dhawan B N Mehrotra and CRay ldquoScreening of Indian plants for biological activityrdquo IndianJournal of Experimental Biology vol 6 no 4 pp 232ndash247 1968

[61] Temjenmongla and A K Yadav ldquoAnticestodal efficacy offolklore medicinal plants of Naga tribes in north-east IndiardquoAfrican Journal of Traditional Complementary and AlternativeMedicines vol 2 pp 129ndash133 2005

[62] T V Tangpu and A K Yadav ldquoAnticestodal efficacy of Psidiumguajava against experimental Hymenolepis diminuta infectionin ratsrdquo Indian Journal of Pharmacology vol 38 no 1 pp 29ndash32 2006

[63] R Singh A Mehta P Mehta and K Shukla ldquoAnthelminticactivity of Rhizome extracts of Curcuma longa and Zingiberofficinalerdquo International Journal of Pharmacy and Pharmaceu-tical Sciences vol 3 no 2 pp 236ndash237 2011

[64] M K Asha D Prashanth B Murali R Padmaja and A AmitldquoAnthelmintic activity of essential oil of Ocimum sanctum andeugenolrdquo Fitoterapia vol 72 no 6 pp 669ndash670 2001

[65] J B Githiori J Hoglund P J Waller and R L Baker ldquoTheanthelmintic efficacy of the plantAlbizia anthelmintica againstthe nematode parasites Haemonchus contortus of sheep andHeligmosomoides polygyrus of micerdquo Veterinary Parasitologyvol 116 no 1 pp 23ndash34 2003

[66] N M Enwerema J I Okoguna C O Wambebea D A Oko-rieb and P A Akahc ldquoAnthelmintic activity of the stem barkextracts of Berlina grandiflora and one of its active principlesBetulinic acidrdquo Phytomedicine vol 8 pp 112ndash114 2001

[67] Z Iqbal M Lateef A Jabber M N Ghayur and A HGilani ldquoIn vitro and in vivo anthelmintic activity of Nicotianatabacum L leaves against gastrointestinal nematodes of sheeprdquoPhytotherapy Research vol 20 no 1 pp 46ndash48 2006

[68] Z Iqbal M Lateef A Jabbar G Muhammad and M N KhanldquoAnthelmintic activity of Calotropis procera (Ait) Ait F flowersin sheeprdquo Journal of Ethnopharmacology vol 102 no 2 pp 256ndash261 2005

Submit your manuscripts athttpwwwhindawicom

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ToxinsJournal of

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Medicinal ChemistryInternational Journal of

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BioMed Research International

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Autoimmune Diseases

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Pharmaceutics

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MEDIATORSINFLAMMATION

of

Page 5: Mallotus philippinensis Muell. Arg (Euphorbiaceae ...

BioMed Research International 5

O

O

O

O

O O

CH2

CH3

CH3

CH3

CH3

H3C

H3C

H3C

H

H

H

HO

HO

HO

HO OH

OH

Figure 9 Kamalachalcone B

O O

OOH

OHOH

HO HO 2

3

45

6

78

9

10

1112

1314

15

1998400

2998400

3998400

4998400

5998400

6998400

7998400

8998400

Figure 10 Mallotophilippen A or 1-[57-dihydroxy-22-dimethyl-6-(246-trihydroxy-3-isobutyryl-5-methyl-benzyl)-2H-chromen-8-yl]-2-methyl-butan-1-one

of M philippinensis subjected to characterization throughcolumn chromatography on a Sephadex LH-20 column usingethanol and acetone-water as the mobile phases tanninsand phenols were quantified Bark extract contains 541mggof total phenolics and infractions ranging from 54mgg(fraction I) to 927mgg (fraction VI) and condensed tanninswere detected in fractions IIndashVI [18 19] In 1989 leaves ofM philippinensis were reported for tannins and other relatedcompounds by Saijo et al [20]

35 Other Compounds Unsaturated fatty acids that is triply-unsatured hydroxy acid kamlolenic acid different fatty acidsand glyceride [21] have been reported from Kamala (Mphilippinensis) seed oil

Resinous coloured material contains active parts of rott-lerin and isorottlerin It also contains homorottlerine red role50 yellow role 5 manure 2 volatile oils tannin gumcitric acid and oxalic acid

4 Pharmacological Activities

41 Antifilarial Activity The effect of aqueous and alcoholicleave extracts of M philippinensis (Lam) Muell was studiedon the spontaneous movements of the whole worm and

O O

OOH

OHOH

HO HO 2

3

45

6

78

9

10

1112

1314

15

1998400

2998400

3998400

4998400

5998400

6998400

7998400

Figure 11 Mallotophilippen B or 1-[6-(3-acetyl-246-trihydroxy-5-methyl-benzyl)-57-dihydroxy-22-dimethyl-2H-chromen-8-yl]-2-methyl-butan-1-one

OH

OH

HO

OHO

Figure 12 Mallotophilippen C or (1-[6-(37-dimethyl-octa-26-dienyl)-57-dihydroxy-22-dimoethyl-2H-chromen-8-yl]-3-(4-hy-droxy-phenyl)-propenone) R = H

OH

OH

OHO

OHO

Figure 13 Mallotophilippen D or 3-(34-dihydroxy-phenyl)-1-[6-(37-dimethyl-octa-26-dienyl)-57-dihydroxy-22-dimethyl-2H-chromen-8-yl]-propenone R = OH

nerve-muscle (nm) preparation of Setaria cervi and on thesurvival of microfilariae in vitro Both the extracts result ininhibition of spontaneous motility of whole worm and thenm preparation of S cervi characterized by initial stimula-tion followed by depression in amplitude The tone and rateof contractions remained visibly unaffected Aqueous extractat higher concentration showed immediate reduction in toneThe concentration required to inhibit the movements of nmpreparation was 15th for aqueous and 111th for alcoholicextract compared to that for the whole worm suggesting acuticular permeability barrier The stimulatory response ofacetylcholine was blocked by aqueous extract onwhole worm

6 BioMed Research International

OH

OH

OH

O

OHO

Figure 14 Mallotophilippen E or 1-[57-dihydroxy-2-methyl-6-(3-methyl-but-2-enyl)-2-(4-methyl-pent-3-enyl)-2H-chromen-8-yl]-3-(34-dihydroxy-phenyl)-propenone

OH

OH

OHOH

O

O

O

HO

Figure 15 Rottlerin

movements On the microfilariae the LC50and LC

90were 18

and 20 ngmL for aqueous and 12 and 15 ngmL for alcoholicextracts respectively [2] Further study will be required toevaluate the same activity with its phytochemicals

42 Antifertility Activity Seeds extract of M philippinensisexhibits adverse effects on different reproductive parametersof female rats According to the study extract reducesserum FSH and LH levels probably by affecting hypotha-lamicpituitary axis in experimental animals This reducedlevel may affect follicular development quality of ovulatedeggs corpus luteum formation estrus cycle andmaintenanceof pregnancy in rats [22] This antifertility effect of plantextract is supposed to be caused by rottlerin (Figure 15) aphloroglucinol derivative Acetyl rottlerin may be active butisorottlerin (Figure 17) is either inactive or slightly active [23]Effect of pure rottlerin can be further studied so as to clarifythe potential of phloroglucinol derivatives

43 Antibacterial and Antifungal Activity A series of 61Indian medicinal plants belonging to 33 different familiesused in various infectious disorders were screened for theirantimicrobial properties Screening was carried out at 1000and 500 120583gmL concentrations by agar dilution methodagainst Bacillus cereus varmycoides Bacillus pumilus Bacillussubtilis Bordetella bronchisepticaMicrococcus Luteus Staphy-lococcus aureus Staphylococcus epidermidis Escherichia coli

OH

OH

O

O

O

HO

HO

HO

Figure 16 Isoallorottlerin

OH

OH

O

O

O

OHO

HO

Figure 17 Isorottlerin

Klebsiella pneumonia Candida albicans and Saccharomycescerevisiae Twenty-eight plant extracts showed activity againstat least one of the test organisms used in the screeningOn the basis of the results obtained study concludes thatthe crude extracts of M philippinensis exhibited significantantimicrobial activity [3] and properties that support folk-loric use in the treatment of some diseases as broad-spectrumantimicrobial agents Steam bark of plant and its chloroformfractions and the methanolic extract significantly inhibitthe pathogenic bacteria with significant zones of inhibitioncomparable to the standard drug used However the hexanicextract did not show any significant activity [24] Glandularhair of fruits of Mallotus exhibits significant antibacterialactivity against human pathogenic bacteria withMIC ranging15ndash20mgmL This extract does not show any inhibitionagainst different species of candida This shows that fruitextract possesses antibacterial activity without any antifungalpotential The results of the study may justify the use of theplant against bacterial pathogens This probably explains theuse of these plants by the indigenous people against a numberof infections [25]

However ethanolic extract shows potent anti-Heli-cobacter pylori activity at the concentration of 156ndash312mgLagainst eight H pylori strains Further purification of extractrevealed that rottlerin exhibits potent bactericidal effectwith minimal bactericidal concentration (MBC) of 312ndash625mgL against different resistant strains of clarithromycin

BioMed Research International 7

M philippinensis

Rottlerin

Fruit

H3C

HO

HO

OH OH

OH

O

O

O

CH3

CH3

CH3

Antifertility

Antimicrobial

Protein inhibition

Antituberculosis activity

Antiallergic activity

Antiproliferative activity

Antiparasitic (cestodal)

Figure 18 Rottlerin and its major biological activities

and metronidazole including Japanese and Pakistani strains[17]

44 Anti-Inflammatory and Immunoregulatory ActivityChalcones derivatives from the fruits of M philippinensisand mallotophilippens C D and E (Figures 12 13 and14) inhibit nitric oxide (NO) production and inducibleNO synthase (iNOS) gene expression by a murinemacrophage-like cell line (RAW 2647) which was activatedby lipopolysaccharide (LPS) and recombinant mouseinterferon-gamma (IFN-gamma) Further investigationssuggest the downregulation of cyclooxygenase-2 geneinterleukin-6 gene and interleukin-1b gene expressionThe above results show that these chalcones have goodanti-inflammatory and immunoregulatory effects [26]

45 Antioxidant Activity and Antiradical Activity Differentfractions of bark and fruit of Mallotus were studied forits total antioxidant activity (TAA) and antiradical activityagainst DPPH on a Sephadex LH-20 column using ethanoland acetone-water asmobile phase Among different extractsbark fraction showed the strongest antiradical activity (TAAvaluemdash527 mmol Trolox equivg) and reducing powerAnother extract that is phenolic fraction shows TAAranging from 058mmol Troloxg (fraction I) to 682mmolTroloxg (fraction IV) this is the strongest fraction showingantiradical activity against DPPH and reducing power TAAof other extracts ranged from 005 to 179mmol Troloxequivg [18 19]

46 Protein Inhibition Implicated in Cancer Processes Proteinkinase is inhibited with some specificity for PKC by rottlerina compound isolated from Mallotus Inhibition of PKCappears due to a strong competition between rottlerin andATP CaM-kinase III is suppressed by rottlerin as effectivelyas PKC 120575 among different protein kinases tested Novelinhibition property and improved selectivity for a distinctPKC isoenzyme of rottlerin are suggestive from its chemicalstructure [27 28] Rottlerin is also very potent in blockingother kinases including AktPKB and p38 MAPK [29ndash31] Italso inhibits human T cell responses [32] reduces MUC5ACexpression in human epithelial cells [33] abrogates reactiveoxygen species production in hepatic stellate cells [34] andprevents histamine-induced H1-receptor gene expression inHeLa cells [35] However still very limited information isavailable of rottlerin towards cancer disease and its mecha-nism of action

47 Hepatoprotective Activity Methanolic extract of Mphilippinensis leaves decreases the CCl

4-induced elevation in

biochemical parameters (SGOT SGPT SALP direct biliru-bin total bilirubin andMDA) on pretreatment at doses 100ndash200mgkg and also reversed the functional and antioxidantparameters This study suggests that leave extract was effec-tive in functional improvement of hepatocytes Histopatho-logical studies also suggest the hepatoprotective activity ofplant [36]

48 In Vitro Cytotoxicity against Human Cancel Cell Glan-dular hair extract of Mallotus fruit powder was assayed

8 BioMed Research International

(a) (b)

(c) (d)

(e)

Figure 19 Mallotus philippinensis (a) Mature plant (b) leaf (c) initial inflorescence of seed setting (d) mature fruits twig (e) mature fruitwith seed

against 14 human cancer cell lines among different fractions95 ethanolic extract showed the highest cytotoxic effect ascompared to 50 ethanolic and aqueous portion Furtherthe chromatographic analysis of the said fraction afforded apolyphenolic molecule rottlerin inMallotus plant [37]

49 Anticestodal ActivityVeterinary Applications M philip-pinensis fruit was found to be very effective against gas-trointestinal cestodes in Beetal goats and other ruminantsComparative anticestodal efficacies of single oral dose treat-ments with the powdered fruit ofM philippinensis (125 250and 375mgkg) its water or methanol extracts (equivalent to375mgkg) and the total glycosides (25 50 and 100mgkg)were determined in naturally cestode-infected Beetal goats[38] An ethnobotanical survey has been conducted foranthelmintics in ruminants so as to document the plantsused to treat and control helminthes Mallotus has beenfrequently used to treat helminthosis in ruminants [39] M

philippinensis fruit extract of 800mgkg twice daily for 3days was observed to have curative efficacy against matureadult worms of Hymenolepis diminuta The total follow-upperiod of 90 days did not show any further excretion of eggsin the faeces of treated rats Praziquantel at the dosage of5mgkg also produced a similar effect [40] In vitro scolicidalactivity ofM philippinensis (Lam)Muell Arg fruit glandularhair extract against hydatid cyst Echinococcus granulosusprotoscoleces at concentrations 10 and 20mgmL shows themortality rate 97 to 99 respectively for 60min treatmentwhile up to 93 mortality was observed with 20mgmLfor only 10min treatment This proves that the extract hassignificant scolicidal activity with almost no associated sideeffects [41] In vivo animal model experiment will be furtherrequired to prove its effect against Hydatid cyst

410 Purgative Activity and Anthelmintic Activity A signifi-cant purgative effect after an oral dose (120mgkg) in rats was

BioMed Research International 9

assessed from resins isolated from plant Its effect was evalu-ated from the weight of faeces as well as from surface areaof blotting paper soaked by liquid faeces The anthelminticeffect on tape worm was evaluated in albino rates fromthe resin of the plant showed lethal effect of 3569 and7821 respectively in small intestine in concentrations 60and 120mgkg respectively [42 43]

411 Antituberculosis Activity Organic extract of plant afterbioassay-directed fractionation yields five compounds themost active of which againstMycobacterium tuberculosis wasa new compound 8-cinnamoyl-57-dihydroxy-22-dimethyl-6-geranylchromene for which the name mallotophilippenF is suggested The second compound 8-cinnamoyl-22-dimethyl-7-hydroxy-5-methoxychromene was isolated froma natural source for the first time while the remaining threecompounds rottlerin isoallorottlerin or isorottlerin andthe so-called ldquored compoundrdquo 8-cinnamoyl-57-dihydroxy-226-trimethylchromene had been already isolated fromthis plant Isolated compounds were identified by 2D-NMRand C-13 NMR [44] Ethanolic extract of plant was assayedfor antimycobacterial activity against M smegmatis by discdiffusion assay Further antituberculosis potential of leavesextract was identified by radiometric BACTEC assay resultrevealed that ethanolic extract ofM philippensis showed anti-tuberculosis activity against virulent and avirulent strains ofM tuberculosis H37Rv andM tuberculosis H37Ra with min-imum inhibitory concentrations of 025 and 0125mgmLminus1respectively The inhibition in growth index values of Mtuberculosis was observed in the presence of ethyl acetatefraction at a minimum concentration of 005mgmLminus1 Itsuggests that ethanolic and ethyl acetate fraction of plantpossesses significant antimycobacterial activity [45] Steambark of M philippinensis has also been reported for itsantitumor promoting effect which was due to the presenceof 3120572-Hydroxy-DA-friedooleanan-2-one [46]

412 Antiallergic Activity M philippinensis fruit containstwo new phloroglucinol derivatives mallotophilippensA and B (Figures 10 and 11) which were identified usingchemical and spectral data as 1-[57-dihydroxy-22-di-methyl-6-(246-trihydroxy-3-isobutyryl-5-methyl-benzyl)-2H-chromen-8-yl]-2-methyl-butan-1-one and 1-[6-(3-Acetyl-246-trihydroxy-5-methyl-benzyl)-57-dihydroxy-22-dim-ethyl-2H-chromen-8-yl]-2-methyl-butan-1-one respe-ctively These compounds inhibited the production ofnitric oxide (NO) and inducible NO synthase (iNOS) geneexpression by a murine macrophage-like cell line (RAW2647) which was activated by lipopolysaccharide (LPS)and recombinant mouse interferon-g (IFN-g) Furtherphloroglucinol derivatives inhibit histamine release from ratperitoneal mast cells induced by compound 4880This studysuggests its anti-inflammatory activity [47] Rottlerin hasbeen tested in animal models of IgE-dependent anaphylaxisand the antiallergic mechanisms of action in mast cellsAntiallergic action of rottlerin has been tested in passivecutaneous anaphylaxis and passive systemic anaphylaxismouse models and in anaphylactic contraction of bronchial

rings isolated from sensitized guinea pigs This experimentsproves antiallergic effect of rottlerin by blocking IgE-inducedmast cell degranulation This report suggests the use ofrottlerin in mast cell-mediated allergic disorders includingurticaria and allergic asthma [48]

413 Anti-Leukaemic Activity Root extract ofM philippinen-sis was tested on human promyelocytic leukemia HL-60 cellproliferation cell cycle regulators and apoptosis in order toinvestigate its antileukemic effect Hexane fraction showedpromising toxicity against p53-deficient HL-60 cells (IC

50

15mg dry roots equivalentmL medium) after 72 h andinterestingly inhibition of cell proliferation was preceded bythe upregulation of the protooncogenes Cdc25A and cyclinD1 within 24 hours suggesting its antileukemic effect inHL-60 cells After isolation and identification by GC-MSpolyphenols were the main compounds of the hexane extractthat inhibited proliferation and induced apoptosis [49]

414 Antiproliferative Activity Antiproliferative effect wasevaluated against Thp-1 cell lines from the isolated com-pounds of M philippinensis fruit extract in which 41015840-hydroxyrottlerin showed 54 growth inhibition ofThp-1 cellline [50] Other isolated compounds were also tested againstdifferent fungi andwere found to be very effective IC

50values

415 Anti-HIV Activity Four phloroglucinol derivativesnamed mallotophenone (5-methylene-bis-26-dihydroxy-3-methyl-4-methoxyacetophenone) mallotochromene (8-acetyl-57-dihydroxy-6-(3-acetyl-24-dihydroxy-5-methyl-6-methoxybenzyl)-22-dimethylchromene) mallotojaponin(3-(33(dimethylallyl) S-(3(acetyl-24-dihydroxy-5-methyl-6-methoxybenzyl)-phloracetophenone) andmallotolerin (3-(3-methyl-2-hydroxybut-3-enyl)-5-(3-acetyl-24-dihydroxy-5-methyl-6-methoxybenzyl)-phloracetophenone) weretested for their ability to inhibit the activity of humanimmunodeficiency virus- (HIV-) reverse transcriptaseThe mode of inhibition of mallotojaponin was foundto be competitive with respect to the template primer(rA)n (dT)12ndash18 and noncompetitive with respect to thetriphosphate substrate dTTPThe Ki value of mallotojaponinfor HIV-reverse transcriptase was determined to be 61 120583M[51]

416 Antitumor Activity Four known friedelane-type trit-erpenoids friedelin 3-hydroxy-DA-friedoolean-3-en-2-one 2120573-hydroxy-DA-friedooleanan-3-one and 3120572-hy-droxy-DA-friedooleanan-2-one and two known lupane-type triterpenoids lupeol and betulin were isolated fromthe stem bark of M philippinensis and were tested fortheir inhibitory effects on Epstein-Barr virus early antigen(EBV-EA) activation induced by 12-O-tetradecanoylphorbol13-acetate (TPA) The inhibitory effect of compounds 2(IC50

= 292mol ratio32 pmolTPA) and 4 (IC50

= 288) wasstronger than those of the other compounds tested and thepositive control curcumin (IC

50= 343) Compound 3120572-

hydroxy-DA-friedooleanan-2-one strongly inhibited mouse

10 BioMed Research International

skin tumor promotion in an in vivo two-stage carcinogenesismodel [46]

417 Wound Healing and Mesenchymal Stem Cell (MSC)Proliferation Bark extract ofMallotus philippinensis has beentested in vitro for wound healing activity by examining theproliferation and migration of MSCs KUM6 cells prolifer-ation and migration have been enhanced at 016ndash4 120583gmLand unregulated the activity of MSCs by secreting variouscytokines to wounded site from bone marrow to systemiccirculation and finally remodel wounded tissues [52]

418 Toxicities Seeds of M philippinensis ethereal extracthave adverse effect on various parameters of female rats Eventhe extract reduces serum levels of gonadotropins in treatedanimals at high dose of 100mgkg body weight Reducedweights of ovary and uterus follicular development andincreased atretic follicular in the ovary are due to subnormallevels of steroid hormones Thus pregnancy is very difficultin female rats treated with kamala seed extract [22]

419 Colouring Agent-Dye Glandular hairs of fruit aremostly used as an orange dye for silk [53 54]

5 Pharmacognostic Evaluation ofMallotus philippinensis

Morphological study shows that fruit depresses globoseand is three-lobed capsule 5ndash7mm times 8ndash10ndash12mm stellate-puberulose and with abundant orange or reddish glan-dular granules Seeds are subglobose and black in colorOrganoleptic property of the red fruit shows that it is tastelessand odourless Microscopic description showed the presenceof epicarp which contained a compactly packed layer ofmucilaginous cells and mesocarp composed of columnarcells which are closely arranged Its polygonal cells are com-pactly arranged in 2-3 layers Presence of lignified vasculararrangement has been observed in the transverse section [55]

6 Conclusion and Future Perspective

Medicinal plants have been clinically used and its interest hasbeen dramatically increased over the past decades throughoutthe world and its formulations are increasingly cited inmedia Daily consumption of the natural products and theirformulations by an extensive number of patients lead toserious concern for scientist to study its efficacy and safetyBecause of extensive use and its benefits natural productsin many countries are regulated both as medicinal productsand as food supplements often labeled as natural foodsupplements

Traditional use and its growing demand for Mallotusphilippinensis and its other species lead to compile this reviewand commented on the current knowledge provided byclinical and preclinical research on the effect of this plant

Mallotus philippinensis has been widely used as tradi-tional medicine in several parts of countries including IndiaEvery part of this plant possesses its specific medicinal prop-erties and is usedmainly in ayurveda to fight against intestinalworms in domestic and grazing animals when administeredwith jaggeryHowever only a few reports are attributed to thisplant and its different parts and there is a large scope for inves-tigation Hence it is required to explore more of its potentialwithin the field of medicinal and pharmaceutical sciences fornovel and fruitful application of this plant in form of naturalformulation Along with this medicinal importance thisplant is used against human pathogens including H pylorianti-inflammatory activity antioxidant antiradical proteininhibition hepatoprotective antiallergic anti-HIV activityand many more Phytochemical investigation revealed that alarge number phenol derivatives and several miscellaneouscompounds from different classes have been isolated fromthis species The phenols diterpenoids steroids flavonoidscardenolides triterpenoids coumarins and isocoumarinsare mostly distributed in all parts of the plant The othermajor isolated pure compounds from this species mostlybelong to phenolic group exhibiting most of the biologicalactivity Various types of extracts from different parts andsingle compounds derived from this species have beenfound to possess biological activities including antioxidantantimicrobial anti-inflammatory cytotoxicity and immunemodulatory Fruit and bark of plant contain condensed tan-nins responsible for antioxidant activity Somenovel chalconederivatives mallotophilippens C D and E were isolatedfrom the fruits of M philippinensis Mallotoxin or rottlerinhas great anticancerous potential Among the ever-anticanceragents rottlerin appears to have great potentiality for beingused in chemotherapy Rottlerin will become a potentialmolecule for research in future to treat cancerous cell as itwill affect cell machineries involved in apoptosis survivaland autophage This suggests the view that this species haspotential to be a beneficial chemotherapeutic remedy

Although the data and other reports provided that thismedicinal plant is of great biological use in different phar-macological activities including anticancer further researchis needed in different areas regarding the toxicity and efficacyof pure phytochemicals isolated from different parts of thisplant More data will be needed from preclinical and clinicalstudies on humans to clarify its potency and safety aslack of knowledge with respect to its adverse effects andmethodological accuracy in the literature limits towardsits standardized formulation Furthermore the mechanismof action of the phytochemicals and extract of Mallotusphilippinensis is unclear more exhaustive studies will beperformed to explore its mechanism and structure activityrelationship among various constituents

In conclusion this review confirms the great potential ofMallotus philippinensis As very limited information is stillknown for this species it leads us to continue the study ondifferent species of Mallotus plant and its interesting phar-macological properties Further natural product chemistryof isolated moiety and its structural analysis of compounds

BioMed Research International 11

responsible for these activities will be an interesting field ofresearch

Conflict of Interests

The authors declare that there is no conflict of interests re-garding the publication of this paper

Acknowledgment

The authors gratefully acknowledge the financial supportprovided by CSIR Government of India New Delhi forawarding SRF in the form of research fellowship

References

[1] C-J Widen and H S Puri ldquoNatural occurrence and chemicalvariability of phloroglucinols inKamalardquoPlantaMedica vol 40no 3 pp 284ndash287 1980

[2] R Singh K C Singhal and N U Khan ldquoAntifilarial activity ofMallotus philippinensisLam on Setaria cervie (Nematoda Filar-ioidea) in-vitrordquo Indian Journal of Physiology andPharmacologyvol 41 no 4 pp 397ndash403 1997

[3] V P Kumar N S Chauhan H Padh and M Rajani ldquoSearchfor antibacterial and antifungal agents from selected Indianmedicinal plantsrdquo Journal of Ethnopharmacology vol 107 no2 pp 182ndash188 2006

[4] S Shrikumar and T K Ravi ldquoApproaches towards developmentand promotion of herbal drugsrdquo Pharmaceutical Reviews vol 1no 1 pp 180ndash183 2007

[5] C Orwa A Mutua and R Kindt ldquoAgroforestree Database atree reference and selection guiderdquo Version 4 0 2009

[6] K Usmanghani A Saeed and M T Alam ldquoIndusynicMedicine Karachirdquo Research Institute of Indusyunic Medicinevol 1997 pp 285ndash287 1997

[7] F Ahmad and S Hashmi ldquoAdulteration in commercial Kamila(Mallotus philippinensisMuell) an anthelmintic drug of reputerdquoHamdard Medicus vol 38 pp 62ndash67 1995

[8] K D Roberts E Weiss and T Reichstein ldquoGlycosides andaglycons CCLII Cardenolides of the seed of Mallotus philip-pinensisrdquo Helvetica Chimica Acta vol 46 pp 2886ndash2893 1963

[9] M Bandopadhyay V K Dhingra and S K Mukerjee ldquoTriter-penoid and other components of Mallotus philippinensisrdquo Phy-tochemistry vol 11 no 4 p 1511 1972

[10] S P Nair and J Madhusudana Rao ldquoKamaladiol-3-acetate fromthe stem bark of Mallotus philippinensisrdquo Phytochemistry vol32 pp 407ndash409 1993

[11] J DWansi JWandjiW A Kamdem et al ldquoTriterpenoids fromDrypetes chevalieri Beille (Euphorbiaceae)rdquo Natural ProductResearch vol 20 no 6 pp 586ndash592 2006

[12] P Castenada A Bahena and E Garcia ldquoChemical studieson Mexican plants used in traditional medicine XXIX Sec-ondary metabolites from the stem bark of Celaeno-dendronmexicanumrdquo Journal of Natural Products vol 56 pp 1575ndash15791993

[13] T Tanaka T Ito M Iinuma Y Takahashi and H NaganawaldquoDimeric chalcone derivatives from Mallotus philippinensisrdquoPhytochemistry vol 48 no 8 pp 1423ndash1427 1998

[14] T M Nguyen V M Chau V K Phan et al ldquoStudy on chemicalconstituents of the leaves of Mallotus philippinensisrdquo Tap ChiHoa Hoc vol 48 pp 352ndash357 2010

[15] M Furusawa Y Ido T Tanaka et al ldquoNovel complex flavonoidsfrom Mallotus philippinensis (Kamala tree)rdquo Helvetica ChimicaActa vol 88 no 5 pp 1048ndash1058 2005

[16] M Lounasmaa C J Widen C M Tuuf and A HuhtikangasldquoOn the phloroglucinol derivatives of Mallotus philippinensisrdquoPlanta Medica vol 28 no 1 pp 16ndash31 1975

[17] S F H Zaidi I Yoshida F Butt et al ldquoPotent bactericidal con-stituents from Mallotus philippinensis against clarithromycinand metronidazole resistant strains of Japanese and Pakistanihelicobacter pylorirdquo Biological and Pharmaceutical Bulletin vol32 no 4 pp 631ndash636 2009

[18] M Arfan H Amin M Karamac et al ldquoAntioxidant activityof extracts of Mallotus philippinensis fruit and barkrdquo Journal ofFood Lipids vol 14 no 3 pp 280ndash297 2007

[19] M Arfan K Hazrat and K Magdalena ldquoAntioxidant activityof phenolic fractions of Mallotus philippinensis bark extractrdquoJournal of Food Science vol 27 no 2 pp 109ndash117 2009

[20] R Saijo G Nonaka and I Nishioka ldquoTannins and related com-pounds LXXXVIII Isolation and characterization of hydrolyz-able tannins fromMallotus japonicus (Thunb)Mueller-Arg andM philippinensis (Lam)Mueller-ArgrdquoChemical amp Pharmaceu-tical Bulletin vol 37 no 11 pp 2940ndash2947 1989

[21] S C Gupta S S Gupta and J S Aggarwal ldquoChemical exami-nation of the seeds of Mallotus philippinensis III Constitutionof kamlolenic acid isolated from the oilrdquo Journal of Scientific ampIndustrial Research vol 12 pp 240ndash242 1953

[22] S C Thakur S S Thakur S K Chaube and S P Singh ldquoAnetheral extract of Kamala (Mallotus philippinensis (Moll Arg)Lam) seed induce adverse effects on reproductive parametersof female ratsrdquo Reproductive Toxicology vol 20 no 1 pp 149ndash156 2005

[23] M L Gujral D R Varma K N Sareen and A K Roy ldquoOralcontraceptives II Antifertility effect ofMallotus philippinensisrdquoIndian Journal of Medical Research vol 48 pp 52ndash58 1960

[24] KMoorthy K Srinivasan C Subramanian CMohanasundariand M Palaniswamy ldquoPhyto-chemical screening and antibac-terial evaluation of stem bark of Mallotus philippinensis varTomentosusrdquoAfrican Journal of Biotechnology vol 6 no 13 pp1521ndash1523 2007

[25] M Gangwar D Kumar R Tilak et al ldquoQualitative phy-tochemical characterization and antibacterial evaluation ofglandular hairs ofMallotus philippinensis fruit extractrdquo Journalof Pharmacy Research vol 4 no 11 pp 4214ndash4216 2011

[26] A Daikonya S Katsuki and S Kitanaka ldquoAntiallergic agentsfrom naturalsources 9 Inhibition of nitric oxide productionby novel chalcone derivatives from Mallotus philippinensis(Euphorbiaceae)rdquo Chemical amp Pharmaceutical Bulletin vol 52no 11 pp 1326ndash1329 2004

[27] M Gschwendt H J Muller K Kielbassa et al ldquoRottlerina novel protein kinase inhibitorrdquo Biochemical and BiophysicalResearch Communications vol 199 no 1 pp 93ndash98 1994

[28] Y F Liao Y C Hung W H Chang et al ldquoThe PKC deltainhibitor rottlerin induces apoptosis of haematopoietic celllines through mitochondrial membrane depolarization andcaspasescascaderdquo Life Sciences vol 77 no 6 pp 707ndash719 2005

[29] H S Kang E K Park K H Kim et al ldquoReceptor activatorof nuclear factor-kappa B is induced by a rottlerin-sensitiveand p38 MAP kinase-dependent pathway during monocytedifferentiationrdquoMolecules and Cells vol 17 no 3 pp 438ndash4452004

12 BioMed Research International

[30] S P Soltoff ldquoRottlerin an inappropriate and ineffectiveinhibitor of PKC120575rdquo Trends in Pharmacological Sciences vol 28no 9 pp 453ndash458 2007

[31] Y Choi D K Kim S S Kang J K Sonn and E J Jin ldquoIntegrinsignaling and cell spreading alterations by rottlerin treatment ofchick limb bud mesenchymal cellsrdquo Biochimie vol 91 no 5 pp624ndash631 2009

[32] C Springael S Thomas S Rahmouni et al ldquoRottlerin inhibitshuman T cell responsesrdquo Biochemical Pharmacology vol 73 no4 pp 515ndash525 2007

[33] J H Choi Y P Hwang E H Han et al ldquoInhibition of acrolein-stimulated MUC5AC expression by Platycodon grandiflorumroot-derived saponin in A549 cellsrdquo Food and Chemical Toxi-cology vol 49 no 9 pp 2157ndash2166 2011

[34] E L M Guimaraes C Empsen A Geerts and L A vanGrunsven ldquoAdvanced glycation end products induce produc-tion of reactive oxygen species via the activation of NADPHoxidase in murine hepatic stellate cellsrdquo Journal of Hepatologyvol 52 no 3 pp 389ndash397 2010

[35] H Mizuguchi T Terao M Kitai et al ldquoInvolvement of pro-tein kinase C120575extracellular signal-regulated kinasepoly(ADP-ribose) polymerase-1 (PARP-1) signaling pathway in histamine-induced up-regulation of histamine H1 receptor gene expres-sion in HeLa cellsrdquo Journal of Biological Chemistry vol 286 no35 pp 30542ndash30551 2011

[36] S Ramakrishna K M Geetha P V V S Bhaskar gopalR P Kumar C P Madav and L Umachandar ldquoEffect ofMallotus PhilippinensisMuell-Arg leaves against hepatotoxicityof Carbon tetrachloride in ratsrdquo International Journal of Phar-maceutical Sciences and Research vol 2 pp 74ndash83 2011

[37] V Sharma ldquoA polyphenolic compound rottlerin demonstratessignificant in vitro cytotoxicity against human cancer celllines isolation and characterization from the fruits ofMallotusphilippinensisrdquo Journal of Plant Biochemistry and Biotechnologyvol 20 no 2 pp 190ndash195 2011

[38] M S Akhtar and I Ahmad ldquoComparative efficacy of Mallotusphilippinensis fruit (Kamala) or Nilzan drug against gastroin-testinal cestodes in Beetal goatsrdquo Small Ruminant Research vol8 no 1-2 pp 121ndash128 1992

[39] A Jabbar M A Raza Z Iqbal and M N Khan ldquoAn inventoryof the ethnobotanicals used as anthelmintics in the southernPunjab (Pakistan)rdquo Journal of Ethnopharmacology vol 108 no1 pp 152ndash154 2006

[40] M Gangwar A Dalai A Chaudhary et al ldquoStudy on activityof alcoholic extract of glands and hairs of fruits of Mallotusphilippinensis in murine cestodal infection modelrdquo Interna-tional Journal of Pharmacy amp Pharmaceutical Sciences vol 4no 1 pp 643ndash645 2012

[41] M Gangwar V C Verma T D Singh S K Singh R KGoel and G Nath ldquoIn-vitro scolicidal activity of Mallotusphilippinensis (Lam) Muell Arg fruit glandular hair extractagainst hydatid cyst Echinococcus granulosusrdquo Asian PacificJournal of Tropical Medicine vol 6 no 8 pp 595ndash601 2013

[42] S S Gupta P Verma and K Hishikar ldquoPurgative andanthelmintic effects of Mallotus philippinensis in rats againsttape wormrdquo Indian Journal of Physiology amp Pharmacology vol28 no 1 pp 63ndash66 1984

[43] A Hussain M N Khan Z Iqbal and M S Sajid ldquoAn accountof the botanical anthelmintics used in traditional veterinarypractices in Sahiwal district of Punjab Pakistanrdquo Journal ofEthnopharmacology vol 119 no 1 pp 185ndash190 2008

[44] Q Hong D E Minter S G Franzblau M Arfan H Amin andM G Reinecke ldquoAnti-tuberculosis compounds from Mallotusphilippinensisrdquo Natural Product Communications vol 5 no 2pp 211ndash217 2010

[45] V K Gupta C Shukla G R S Bisht D Saikia S Kumarand R L Thakur ldquoDetection of anti-tuberculosis activity insome folklore plants by radiometric BACTEC assayrdquo Letters inApplied Microbiology vol 52 no 1 pp 33ndash40 2011

[46] R Tanaka T Nakata C Yamaguchi S Wada T Yamadaand H Tokuda ldquoPotential anti-tumor-promoting activity of3120572-Hydroxy-D a-friedooleanan-2-one from the stem bark ofMallotus philippinensisrdquo Planta Medica vol 74 no 4 pp 413ndash416 2008

[47] A Daikonya S Katsuki J B Wu and S Kitanaka ldquoAnti-allergic agents from natural sources (4) anti-allergic activityof new phloroglucinol derivatives from Mallotus philippinensis(Euphorbiaceae)rdquo Chemical and Pharmaceutical Bulletin vol50 no 12 pp 1566ndash1569 2002

[48] T K Chan S W David C Cheng S P Guan H MKoh and W S Wong ldquoAnti-allergic actions of rottlerin fromMallotus philippinensisis in experimental mast cell-mediatedanaphylactic modelsrdquo Phytomedicine vol 20 no 10 pp 853ndash860 2013

[49] M Khan R A Qureshi M Hussain K Mehmood and R AKhan ldquoHexane soluble extract ofMallotus philippinensis (Lam)Muell Arg root possesses anti-leukaemic activityrdquo ChemistryCentral Journal vol 7 no 1 article 157 2013

[50] R Roshan S G Kulkarni S P Tupe et al ldquoAntifungal dimericchalcone derivative kamalachalcone E from Mallotus philip-pinensisrdquo Natural Product Research Formerly Natural ProductLetters vol 28 no 4 pp 245ndash250 2014

[51] H Nakane M Arisawa A Fujita S Koshimura and KOno ldquoInhibition of HIV-reverse transcriptase activity by somephloroglucinol derivativesrdquo FEBS Letters vol 286 no 1-2 pp83ndash85 1991

[52] T Furumoto N Ozawa Y Inami et al ldquoMallotus philippinensisbark extracts promote preferential migration of mesenchymalstem cells and improve wound healing in micerdquo Phytomedicinevol 21 no 3 pp 247ndash253 2014

[53] Maeda ldquoMethod for producing Mallotus philippinensis dyecomposition and the compositionrdquo US7556829 B2 2009

[54] C Wiart Medicinal Plants of the Asia-Pacific Drugs for theFutureWorld Scientific Singapore 2006

[55] V R Sharma ldquoA review on endangered plant of Mallotusphilippinensis (Lam) MArgrdquo Pharmacologyonline vol 3 pp1256ndash1265 2011

[56] V Tangpu T Temjenmongla and A K Yadav ldquoAnticestodalproperty of Strobilanthes discolor an experimental study inHymenolepis diminutamdashratmodelrdquo Journal of Ethnopharmacol-ogy vol 105 no 3 pp 459ndash463 2006

[57] V Tangpu K Temjenmongla and A K Yadav ldquoAnticestodalactivity ofTrifolium repens extractrdquo Pharmaceutical Biology vol42 no 8 pp 656ndash658 2004

[58] A K Yadav and T Temjenmongla ldquoAnticestodal activity ofHouttuynia cordata leaf extract againstHymenolepis diminuta inexperimentally infected ratsrdquo Journal of Parasitic Diseases vol35 no 2 pp 190ndash194 2011

[59] T Temjenmongla and A K Yadav ldquoAnticestodal efficacy ofLasia spinosa extract against experimental Hymenolepis dimin-uta infections in ratsrdquo Pharmaceutical Biology vol 44 no 7 pp499ndash502 2006

BioMed Research International 13

[60] M L Dhar M M Dhar B N Dhawan B N Mehrotra and CRay ldquoScreening of Indian plants for biological activityrdquo IndianJournal of Experimental Biology vol 6 no 4 pp 232ndash247 1968

[61] Temjenmongla and A K Yadav ldquoAnticestodal efficacy offolklore medicinal plants of Naga tribes in north-east IndiardquoAfrican Journal of Traditional Complementary and AlternativeMedicines vol 2 pp 129ndash133 2005

[62] T V Tangpu and A K Yadav ldquoAnticestodal efficacy of Psidiumguajava against experimental Hymenolepis diminuta infectionin ratsrdquo Indian Journal of Pharmacology vol 38 no 1 pp 29ndash32 2006

[63] R Singh A Mehta P Mehta and K Shukla ldquoAnthelminticactivity of Rhizome extracts of Curcuma longa and Zingiberofficinalerdquo International Journal of Pharmacy and Pharmaceu-tical Sciences vol 3 no 2 pp 236ndash237 2011

[64] M K Asha D Prashanth B Murali R Padmaja and A AmitldquoAnthelmintic activity of essential oil of Ocimum sanctum andeugenolrdquo Fitoterapia vol 72 no 6 pp 669ndash670 2001

[65] J B Githiori J Hoglund P J Waller and R L Baker ldquoTheanthelmintic efficacy of the plantAlbizia anthelmintica againstthe nematode parasites Haemonchus contortus of sheep andHeligmosomoides polygyrus of micerdquo Veterinary Parasitologyvol 116 no 1 pp 23ndash34 2003

[66] N M Enwerema J I Okoguna C O Wambebea D A Oko-rieb and P A Akahc ldquoAnthelmintic activity of the stem barkextracts of Berlina grandiflora and one of its active principlesBetulinic acidrdquo Phytomedicine vol 8 pp 112ndash114 2001

[67] Z Iqbal M Lateef A Jabber M N Ghayur and A HGilani ldquoIn vitro and in vivo anthelmintic activity of Nicotianatabacum L leaves against gastrointestinal nematodes of sheeprdquoPhytotherapy Research vol 20 no 1 pp 46ndash48 2006

[68] Z Iqbal M Lateef A Jabbar G Muhammad and M N KhanldquoAnthelmintic activity of Calotropis procera (Ait) Ait F flowersin sheeprdquo Journal of Ethnopharmacology vol 102 no 2 pp 256ndash261 2005

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MEDIATORSINFLAMMATION

of

Page 6: Mallotus philippinensis Muell. Arg (Euphorbiaceae ...

6 BioMed Research International

OH

OH

OH

O

OHO

Figure 14 Mallotophilippen E or 1-[57-dihydroxy-2-methyl-6-(3-methyl-but-2-enyl)-2-(4-methyl-pent-3-enyl)-2H-chromen-8-yl]-3-(34-dihydroxy-phenyl)-propenone

OH

OH

OHOH

O

O

O

HO

Figure 15 Rottlerin

movements On the microfilariae the LC50and LC

90were 18

and 20 ngmL for aqueous and 12 and 15 ngmL for alcoholicextracts respectively [2] Further study will be required toevaluate the same activity with its phytochemicals

42 Antifertility Activity Seeds extract of M philippinensisexhibits adverse effects on different reproductive parametersof female rats According to the study extract reducesserum FSH and LH levels probably by affecting hypotha-lamicpituitary axis in experimental animals This reducedlevel may affect follicular development quality of ovulatedeggs corpus luteum formation estrus cycle andmaintenanceof pregnancy in rats [22] This antifertility effect of plantextract is supposed to be caused by rottlerin (Figure 15) aphloroglucinol derivative Acetyl rottlerin may be active butisorottlerin (Figure 17) is either inactive or slightly active [23]Effect of pure rottlerin can be further studied so as to clarifythe potential of phloroglucinol derivatives

43 Antibacterial and Antifungal Activity A series of 61Indian medicinal plants belonging to 33 different familiesused in various infectious disorders were screened for theirantimicrobial properties Screening was carried out at 1000and 500 120583gmL concentrations by agar dilution methodagainst Bacillus cereus varmycoides Bacillus pumilus Bacillussubtilis Bordetella bronchisepticaMicrococcus Luteus Staphy-lococcus aureus Staphylococcus epidermidis Escherichia coli

OH

OH

O

O

O

HO

HO

HO

Figure 16 Isoallorottlerin

OH

OH

O

O

O

OHO

HO

Figure 17 Isorottlerin

Klebsiella pneumonia Candida albicans and Saccharomycescerevisiae Twenty-eight plant extracts showed activity againstat least one of the test organisms used in the screeningOn the basis of the results obtained study concludes thatthe crude extracts of M philippinensis exhibited significantantimicrobial activity [3] and properties that support folk-loric use in the treatment of some diseases as broad-spectrumantimicrobial agents Steam bark of plant and its chloroformfractions and the methanolic extract significantly inhibitthe pathogenic bacteria with significant zones of inhibitioncomparable to the standard drug used However the hexanicextract did not show any significant activity [24] Glandularhair of fruits of Mallotus exhibits significant antibacterialactivity against human pathogenic bacteria withMIC ranging15ndash20mgmL This extract does not show any inhibitionagainst different species of candida This shows that fruitextract possesses antibacterial activity without any antifungalpotential The results of the study may justify the use of theplant against bacterial pathogens This probably explains theuse of these plants by the indigenous people against a numberof infections [25]

However ethanolic extract shows potent anti-Heli-cobacter pylori activity at the concentration of 156ndash312mgLagainst eight H pylori strains Further purification of extractrevealed that rottlerin exhibits potent bactericidal effectwith minimal bactericidal concentration (MBC) of 312ndash625mgL against different resistant strains of clarithromycin

BioMed Research International 7

M philippinensis

Rottlerin

Fruit

H3C

HO

HO

OH OH

OH

O

O

O

CH3

CH3

CH3

Antifertility

Antimicrobial

Protein inhibition

Antituberculosis activity

Antiallergic activity

Antiproliferative activity

Antiparasitic (cestodal)

Figure 18 Rottlerin and its major biological activities

and metronidazole including Japanese and Pakistani strains[17]

44 Anti-Inflammatory and Immunoregulatory ActivityChalcones derivatives from the fruits of M philippinensisand mallotophilippens C D and E (Figures 12 13 and14) inhibit nitric oxide (NO) production and inducibleNO synthase (iNOS) gene expression by a murinemacrophage-like cell line (RAW 2647) which was activatedby lipopolysaccharide (LPS) and recombinant mouseinterferon-gamma (IFN-gamma) Further investigationssuggest the downregulation of cyclooxygenase-2 geneinterleukin-6 gene and interleukin-1b gene expressionThe above results show that these chalcones have goodanti-inflammatory and immunoregulatory effects [26]

45 Antioxidant Activity and Antiradical Activity Differentfractions of bark and fruit of Mallotus were studied forits total antioxidant activity (TAA) and antiradical activityagainst DPPH on a Sephadex LH-20 column using ethanoland acetone-water asmobile phase Among different extractsbark fraction showed the strongest antiradical activity (TAAvaluemdash527 mmol Trolox equivg) and reducing powerAnother extract that is phenolic fraction shows TAAranging from 058mmol Troloxg (fraction I) to 682mmolTroloxg (fraction IV) this is the strongest fraction showingantiradical activity against DPPH and reducing power TAAof other extracts ranged from 005 to 179mmol Troloxequivg [18 19]

46 Protein Inhibition Implicated in Cancer Processes Proteinkinase is inhibited with some specificity for PKC by rottlerina compound isolated from Mallotus Inhibition of PKCappears due to a strong competition between rottlerin andATP CaM-kinase III is suppressed by rottlerin as effectivelyas PKC 120575 among different protein kinases tested Novelinhibition property and improved selectivity for a distinctPKC isoenzyme of rottlerin are suggestive from its chemicalstructure [27 28] Rottlerin is also very potent in blockingother kinases including AktPKB and p38 MAPK [29ndash31] Italso inhibits human T cell responses [32] reduces MUC5ACexpression in human epithelial cells [33] abrogates reactiveoxygen species production in hepatic stellate cells [34] andprevents histamine-induced H1-receptor gene expression inHeLa cells [35] However still very limited information isavailable of rottlerin towards cancer disease and its mecha-nism of action

47 Hepatoprotective Activity Methanolic extract of Mphilippinensis leaves decreases the CCl

4-induced elevation in

biochemical parameters (SGOT SGPT SALP direct biliru-bin total bilirubin andMDA) on pretreatment at doses 100ndash200mgkg and also reversed the functional and antioxidantparameters This study suggests that leave extract was effec-tive in functional improvement of hepatocytes Histopatho-logical studies also suggest the hepatoprotective activity ofplant [36]

48 In Vitro Cytotoxicity against Human Cancel Cell Glan-dular hair extract of Mallotus fruit powder was assayed

8 BioMed Research International

(a) (b)

(c) (d)

(e)

Figure 19 Mallotus philippinensis (a) Mature plant (b) leaf (c) initial inflorescence of seed setting (d) mature fruits twig (e) mature fruitwith seed

against 14 human cancer cell lines among different fractions95 ethanolic extract showed the highest cytotoxic effect ascompared to 50 ethanolic and aqueous portion Furtherthe chromatographic analysis of the said fraction afforded apolyphenolic molecule rottlerin inMallotus plant [37]

49 Anticestodal ActivityVeterinary Applications M philip-pinensis fruit was found to be very effective against gas-trointestinal cestodes in Beetal goats and other ruminantsComparative anticestodal efficacies of single oral dose treat-ments with the powdered fruit ofM philippinensis (125 250and 375mgkg) its water or methanol extracts (equivalent to375mgkg) and the total glycosides (25 50 and 100mgkg)were determined in naturally cestode-infected Beetal goats[38] An ethnobotanical survey has been conducted foranthelmintics in ruminants so as to document the plantsused to treat and control helminthes Mallotus has beenfrequently used to treat helminthosis in ruminants [39] M

philippinensis fruit extract of 800mgkg twice daily for 3days was observed to have curative efficacy against matureadult worms of Hymenolepis diminuta The total follow-upperiod of 90 days did not show any further excretion of eggsin the faeces of treated rats Praziquantel at the dosage of5mgkg also produced a similar effect [40] In vitro scolicidalactivity ofM philippinensis (Lam)Muell Arg fruit glandularhair extract against hydatid cyst Echinococcus granulosusprotoscoleces at concentrations 10 and 20mgmL shows themortality rate 97 to 99 respectively for 60min treatmentwhile up to 93 mortality was observed with 20mgmLfor only 10min treatment This proves that the extract hassignificant scolicidal activity with almost no associated sideeffects [41] In vivo animal model experiment will be furtherrequired to prove its effect against Hydatid cyst

410 Purgative Activity and Anthelmintic Activity A signifi-cant purgative effect after an oral dose (120mgkg) in rats was

BioMed Research International 9

assessed from resins isolated from plant Its effect was evalu-ated from the weight of faeces as well as from surface areaof blotting paper soaked by liquid faeces The anthelminticeffect on tape worm was evaluated in albino rates fromthe resin of the plant showed lethal effect of 3569 and7821 respectively in small intestine in concentrations 60and 120mgkg respectively [42 43]

411 Antituberculosis Activity Organic extract of plant afterbioassay-directed fractionation yields five compounds themost active of which againstMycobacterium tuberculosis wasa new compound 8-cinnamoyl-57-dihydroxy-22-dimethyl-6-geranylchromene for which the name mallotophilippenF is suggested The second compound 8-cinnamoyl-22-dimethyl-7-hydroxy-5-methoxychromene was isolated froma natural source for the first time while the remaining threecompounds rottlerin isoallorottlerin or isorottlerin andthe so-called ldquored compoundrdquo 8-cinnamoyl-57-dihydroxy-226-trimethylchromene had been already isolated fromthis plant Isolated compounds were identified by 2D-NMRand C-13 NMR [44] Ethanolic extract of plant was assayedfor antimycobacterial activity against M smegmatis by discdiffusion assay Further antituberculosis potential of leavesextract was identified by radiometric BACTEC assay resultrevealed that ethanolic extract ofM philippensis showed anti-tuberculosis activity against virulent and avirulent strains ofM tuberculosis H37Rv andM tuberculosis H37Ra with min-imum inhibitory concentrations of 025 and 0125mgmLminus1respectively The inhibition in growth index values of Mtuberculosis was observed in the presence of ethyl acetatefraction at a minimum concentration of 005mgmLminus1 Itsuggests that ethanolic and ethyl acetate fraction of plantpossesses significant antimycobacterial activity [45] Steambark of M philippinensis has also been reported for itsantitumor promoting effect which was due to the presenceof 3120572-Hydroxy-DA-friedooleanan-2-one [46]

412 Antiallergic Activity M philippinensis fruit containstwo new phloroglucinol derivatives mallotophilippensA and B (Figures 10 and 11) which were identified usingchemical and spectral data as 1-[57-dihydroxy-22-di-methyl-6-(246-trihydroxy-3-isobutyryl-5-methyl-benzyl)-2H-chromen-8-yl]-2-methyl-butan-1-one and 1-[6-(3-Acetyl-246-trihydroxy-5-methyl-benzyl)-57-dihydroxy-22-dim-ethyl-2H-chromen-8-yl]-2-methyl-butan-1-one respe-ctively These compounds inhibited the production ofnitric oxide (NO) and inducible NO synthase (iNOS) geneexpression by a murine macrophage-like cell line (RAW2647) which was activated by lipopolysaccharide (LPS)and recombinant mouse interferon-g (IFN-g) Furtherphloroglucinol derivatives inhibit histamine release from ratperitoneal mast cells induced by compound 4880This studysuggests its anti-inflammatory activity [47] Rottlerin hasbeen tested in animal models of IgE-dependent anaphylaxisand the antiallergic mechanisms of action in mast cellsAntiallergic action of rottlerin has been tested in passivecutaneous anaphylaxis and passive systemic anaphylaxismouse models and in anaphylactic contraction of bronchial

rings isolated from sensitized guinea pigs This experimentsproves antiallergic effect of rottlerin by blocking IgE-inducedmast cell degranulation This report suggests the use ofrottlerin in mast cell-mediated allergic disorders includingurticaria and allergic asthma [48]

413 Anti-Leukaemic Activity Root extract ofM philippinen-sis was tested on human promyelocytic leukemia HL-60 cellproliferation cell cycle regulators and apoptosis in order toinvestigate its antileukemic effect Hexane fraction showedpromising toxicity against p53-deficient HL-60 cells (IC

50

15mg dry roots equivalentmL medium) after 72 h andinterestingly inhibition of cell proliferation was preceded bythe upregulation of the protooncogenes Cdc25A and cyclinD1 within 24 hours suggesting its antileukemic effect inHL-60 cells After isolation and identification by GC-MSpolyphenols were the main compounds of the hexane extractthat inhibited proliferation and induced apoptosis [49]

414 Antiproliferative Activity Antiproliferative effect wasevaluated against Thp-1 cell lines from the isolated com-pounds of M philippinensis fruit extract in which 41015840-hydroxyrottlerin showed 54 growth inhibition ofThp-1 cellline [50] Other isolated compounds were also tested againstdifferent fungi andwere found to be very effective IC

50values

415 Anti-HIV Activity Four phloroglucinol derivativesnamed mallotophenone (5-methylene-bis-26-dihydroxy-3-methyl-4-methoxyacetophenone) mallotochromene (8-acetyl-57-dihydroxy-6-(3-acetyl-24-dihydroxy-5-methyl-6-methoxybenzyl)-22-dimethylchromene) mallotojaponin(3-(33(dimethylallyl) S-(3(acetyl-24-dihydroxy-5-methyl-6-methoxybenzyl)-phloracetophenone) andmallotolerin (3-(3-methyl-2-hydroxybut-3-enyl)-5-(3-acetyl-24-dihydroxy-5-methyl-6-methoxybenzyl)-phloracetophenone) weretested for their ability to inhibit the activity of humanimmunodeficiency virus- (HIV-) reverse transcriptaseThe mode of inhibition of mallotojaponin was foundto be competitive with respect to the template primer(rA)n (dT)12ndash18 and noncompetitive with respect to thetriphosphate substrate dTTPThe Ki value of mallotojaponinfor HIV-reverse transcriptase was determined to be 61 120583M[51]

416 Antitumor Activity Four known friedelane-type trit-erpenoids friedelin 3-hydroxy-DA-friedoolean-3-en-2-one 2120573-hydroxy-DA-friedooleanan-3-one and 3120572-hy-droxy-DA-friedooleanan-2-one and two known lupane-type triterpenoids lupeol and betulin were isolated fromthe stem bark of M philippinensis and were tested fortheir inhibitory effects on Epstein-Barr virus early antigen(EBV-EA) activation induced by 12-O-tetradecanoylphorbol13-acetate (TPA) The inhibitory effect of compounds 2(IC50

= 292mol ratio32 pmolTPA) and 4 (IC50

= 288) wasstronger than those of the other compounds tested and thepositive control curcumin (IC

50= 343) Compound 3120572-

hydroxy-DA-friedooleanan-2-one strongly inhibited mouse

10 BioMed Research International

skin tumor promotion in an in vivo two-stage carcinogenesismodel [46]

417 Wound Healing and Mesenchymal Stem Cell (MSC)Proliferation Bark extract ofMallotus philippinensis has beentested in vitro for wound healing activity by examining theproliferation and migration of MSCs KUM6 cells prolifer-ation and migration have been enhanced at 016ndash4 120583gmLand unregulated the activity of MSCs by secreting variouscytokines to wounded site from bone marrow to systemiccirculation and finally remodel wounded tissues [52]

418 Toxicities Seeds of M philippinensis ethereal extracthave adverse effect on various parameters of female rats Eventhe extract reduces serum levels of gonadotropins in treatedanimals at high dose of 100mgkg body weight Reducedweights of ovary and uterus follicular development andincreased atretic follicular in the ovary are due to subnormallevels of steroid hormones Thus pregnancy is very difficultin female rats treated with kamala seed extract [22]

419 Colouring Agent-Dye Glandular hairs of fruit aremostly used as an orange dye for silk [53 54]

5 Pharmacognostic Evaluation ofMallotus philippinensis

Morphological study shows that fruit depresses globoseand is three-lobed capsule 5ndash7mm times 8ndash10ndash12mm stellate-puberulose and with abundant orange or reddish glan-dular granules Seeds are subglobose and black in colorOrganoleptic property of the red fruit shows that it is tastelessand odourless Microscopic description showed the presenceof epicarp which contained a compactly packed layer ofmucilaginous cells and mesocarp composed of columnarcells which are closely arranged Its polygonal cells are com-pactly arranged in 2-3 layers Presence of lignified vasculararrangement has been observed in the transverse section [55]

6 Conclusion and Future Perspective

Medicinal plants have been clinically used and its interest hasbeen dramatically increased over the past decades throughoutthe world and its formulations are increasingly cited inmedia Daily consumption of the natural products and theirformulations by an extensive number of patients lead toserious concern for scientist to study its efficacy and safetyBecause of extensive use and its benefits natural productsin many countries are regulated both as medicinal productsand as food supplements often labeled as natural foodsupplements

Traditional use and its growing demand for Mallotusphilippinensis and its other species lead to compile this reviewand commented on the current knowledge provided byclinical and preclinical research on the effect of this plant

Mallotus philippinensis has been widely used as tradi-tional medicine in several parts of countries including IndiaEvery part of this plant possesses its specific medicinal prop-erties and is usedmainly in ayurveda to fight against intestinalworms in domestic and grazing animals when administeredwith jaggeryHowever only a few reports are attributed to thisplant and its different parts and there is a large scope for inves-tigation Hence it is required to explore more of its potentialwithin the field of medicinal and pharmaceutical sciences fornovel and fruitful application of this plant in form of naturalformulation Along with this medicinal importance thisplant is used against human pathogens including H pylorianti-inflammatory activity antioxidant antiradical proteininhibition hepatoprotective antiallergic anti-HIV activityand many more Phytochemical investigation revealed that alarge number phenol derivatives and several miscellaneouscompounds from different classes have been isolated fromthis species The phenols diterpenoids steroids flavonoidscardenolides triterpenoids coumarins and isocoumarinsare mostly distributed in all parts of the plant The othermajor isolated pure compounds from this species mostlybelong to phenolic group exhibiting most of the biologicalactivity Various types of extracts from different parts andsingle compounds derived from this species have beenfound to possess biological activities including antioxidantantimicrobial anti-inflammatory cytotoxicity and immunemodulatory Fruit and bark of plant contain condensed tan-nins responsible for antioxidant activity Somenovel chalconederivatives mallotophilippens C D and E were isolatedfrom the fruits of M philippinensis Mallotoxin or rottlerinhas great anticancerous potential Among the ever-anticanceragents rottlerin appears to have great potentiality for beingused in chemotherapy Rottlerin will become a potentialmolecule for research in future to treat cancerous cell as itwill affect cell machineries involved in apoptosis survivaland autophage This suggests the view that this species haspotential to be a beneficial chemotherapeutic remedy

Although the data and other reports provided that thismedicinal plant is of great biological use in different phar-macological activities including anticancer further researchis needed in different areas regarding the toxicity and efficacyof pure phytochemicals isolated from different parts of thisplant More data will be needed from preclinical and clinicalstudies on humans to clarify its potency and safety aslack of knowledge with respect to its adverse effects andmethodological accuracy in the literature limits towardsits standardized formulation Furthermore the mechanismof action of the phytochemicals and extract of Mallotusphilippinensis is unclear more exhaustive studies will beperformed to explore its mechanism and structure activityrelationship among various constituents

In conclusion this review confirms the great potential ofMallotus philippinensis As very limited information is stillknown for this species it leads us to continue the study ondifferent species of Mallotus plant and its interesting phar-macological properties Further natural product chemistryof isolated moiety and its structural analysis of compounds

BioMed Research International 11

responsible for these activities will be an interesting field ofresearch

Conflict of Interests

The authors declare that there is no conflict of interests re-garding the publication of this paper

Acknowledgment

The authors gratefully acknowledge the financial supportprovided by CSIR Government of India New Delhi forawarding SRF in the form of research fellowship

References

[1] C-J Widen and H S Puri ldquoNatural occurrence and chemicalvariability of phloroglucinols inKamalardquoPlantaMedica vol 40no 3 pp 284ndash287 1980

[2] R Singh K C Singhal and N U Khan ldquoAntifilarial activity ofMallotus philippinensisLam on Setaria cervie (Nematoda Filar-ioidea) in-vitrordquo Indian Journal of Physiology andPharmacologyvol 41 no 4 pp 397ndash403 1997

[3] V P Kumar N S Chauhan H Padh and M Rajani ldquoSearchfor antibacterial and antifungal agents from selected Indianmedicinal plantsrdquo Journal of Ethnopharmacology vol 107 no2 pp 182ndash188 2006

[4] S Shrikumar and T K Ravi ldquoApproaches towards developmentand promotion of herbal drugsrdquo Pharmaceutical Reviews vol 1no 1 pp 180ndash183 2007

[5] C Orwa A Mutua and R Kindt ldquoAgroforestree Database atree reference and selection guiderdquo Version 4 0 2009

[6] K Usmanghani A Saeed and M T Alam ldquoIndusynicMedicine Karachirdquo Research Institute of Indusyunic Medicinevol 1997 pp 285ndash287 1997

[7] F Ahmad and S Hashmi ldquoAdulteration in commercial Kamila(Mallotus philippinensisMuell) an anthelmintic drug of reputerdquoHamdard Medicus vol 38 pp 62ndash67 1995

[8] K D Roberts E Weiss and T Reichstein ldquoGlycosides andaglycons CCLII Cardenolides of the seed of Mallotus philip-pinensisrdquo Helvetica Chimica Acta vol 46 pp 2886ndash2893 1963

[9] M Bandopadhyay V K Dhingra and S K Mukerjee ldquoTriter-penoid and other components of Mallotus philippinensisrdquo Phy-tochemistry vol 11 no 4 p 1511 1972

[10] S P Nair and J Madhusudana Rao ldquoKamaladiol-3-acetate fromthe stem bark of Mallotus philippinensisrdquo Phytochemistry vol32 pp 407ndash409 1993

[11] J DWansi JWandjiW A Kamdem et al ldquoTriterpenoids fromDrypetes chevalieri Beille (Euphorbiaceae)rdquo Natural ProductResearch vol 20 no 6 pp 586ndash592 2006

[12] P Castenada A Bahena and E Garcia ldquoChemical studieson Mexican plants used in traditional medicine XXIX Sec-ondary metabolites from the stem bark of Celaeno-dendronmexicanumrdquo Journal of Natural Products vol 56 pp 1575ndash15791993

[13] T Tanaka T Ito M Iinuma Y Takahashi and H NaganawaldquoDimeric chalcone derivatives from Mallotus philippinensisrdquoPhytochemistry vol 48 no 8 pp 1423ndash1427 1998

[14] T M Nguyen V M Chau V K Phan et al ldquoStudy on chemicalconstituents of the leaves of Mallotus philippinensisrdquo Tap ChiHoa Hoc vol 48 pp 352ndash357 2010

[15] M Furusawa Y Ido T Tanaka et al ldquoNovel complex flavonoidsfrom Mallotus philippinensis (Kamala tree)rdquo Helvetica ChimicaActa vol 88 no 5 pp 1048ndash1058 2005

[16] M Lounasmaa C J Widen C M Tuuf and A HuhtikangasldquoOn the phloroglucinol derivatives of Mallotus philippinensisrdquoPlanta Medica vol 28 no 1 pp 16ndash31 1975

[17] S F H Zaidi I Yoshida F Butt et al ldquoPotent bactericidal con-stituents from Mallotus philippinensis against clarithromycinand metronidazole resistant strains of Japanese and Pakistanihelicobacter pylorirdquo Biological and Pharmaceutical Bulletin vol32 no 4 pp 631ndash636 2009

[18] M Arfan H Amin M Karamac et al ldquoAntioxidant activityof extracts of Mallotus philippinensis fruit and barkrdquo Journal ofFood Lipids vol 14 no 3 pp 280ndash297 2007

[19] M Arfan K Hazrat and K Magdalena ldquoAntioxidant activityof phenolic fractions of Mallotus philippinensis bark extractrdquoJournal of Food Science vol 27 no 2 pp 109ndash117 2009

[20] R Saijo G Nonaka and I Nishioka ldquoTannins and related com-pounds LXXXVIII Isolation and characterization of hydrolyz-able tannins fromMallotus japonicus (Thunb)Mueller-Arg andM philippinensis (Lam)Mueller-ArgrdquoChemical amp Pharmaceu-tical Bulletin vol 37 no 11 pp 2940ndash2947 1989

[21] S C Gupta S S Gupta and J S Aggarwal ldquoChemical exami-nation of the seeds of Mallotus philippinensis III Constitutionof kamlolenic acid isolated from the oilrdquo Journal of Scientific ampIndustrial Research vol 12 pp 240ndash242 1953

[22] S C Thakur S S Thakur S K Chaube and S P Singh ldquoAnetheral extract of Kamala (Mallotus philippinensis (Moll Arg)Lam) seed induce adverse effects on reproductive parametersof female ratsrdquo Reproductive Toxicology vol 20 no 1 pp 149ndash156 2005

[23] M L Gujral D R Varma K N Sareen and A K Roy ldquoOralcontraceptives II Antifertility effect ofMallotus philippinensisrdquoIndian Journal of Medical Research vol 48 pp 52ndash58 1960

[24] KMoorthy K Srinivasan C Subramanian CMohanasundariand M Palaniswamy ldquoPhyto-chemical screening and antibac-terial evaluation of stem bark of Mallotus philippinensis varTomentosusrdquoAfrican Journal of Biotechnology vol 6 no 13 pp1521ndash1523 2007

[25] M Gangwar D Kumar R Tilak et al ldquoQualitative phy-tochemical characterization and antibacterial evaluation ofglandular hairs ofMallotus philippinensis fruit extractrdquo Journalof Pharmacy Research vol 4 no 11 pp 4214ndash4216 2011

[26] A Daikonya S Katsuki and S Kitanaka ldquoAntiallergic agentsfrom naturalsources 9 Inhibition of nitric oxide productionby novel chalcone derivatives from Mallotus philippinensis(Euphorbiaceae)rdquo Chemical amp Pharmaceutical Bulletin vol 52no 11 pp 1326ndash1329 2004

[27] M Gschwendt H J Muller K Kielbassa et al ldquoRottlerina novel protein kinase inhibitorrdquo Biochemical and BiophysicalResearch Communications vol 199 no 1 pp 93ndash98 1994

[28] Y F Liao Y C Hung W H Chang et al ldquoThe PKC deltainhibitor rottlerin induces apoptosis of haematopoietic celllines through mitochondrial membrane depolarization andcaspasescascaderdquo Life Sciences vol 77 no 6 pp 707ndash719 2005

[29] H S Kang E K Park K H Kim et al ldquoReceptor activatorof nuclear factor-kappa B is induced by a rottlerin-sensitiveand p38 MAP kinase-dependent pathway during monocytedifferentiationrdquoMolecules and Cells vol 17 no 3 pp 438ndash4452004

12 BioMed Research International

[30] S P Soltoff ldquoRottlerin an inappropriate and ineffectiveinhibitor of PKC120575rdquo Trends in Pharmacological Sciences vol 28no 9 pp 453ndash458 2007

[31] Y Choi D K Kim S S Kang J K Sonn and E J Jin ldquoIntegrinsignaling and cell spreading alterations by rottlerin treatment ofchick limb bud mesenchymal cellsrdquo Biochimie vol 91 no 5 pp624ndash631 2009

[32] C Springael S Thomas S Rahmouni et al ldquoRottlerin inhibitshuman T cell responsesrdquo Biochemical Pharmacology vol 73 no4 pp 515ndash525 2007

[33] J H Choi Y P Hwang E H Han et al ldquoInhibition of acrolein-stimulated MUC5AC expression by Platycodon grandiflorumroot-derived saponin in A549 cellsrdquo Food and Chemical Toxi-cology vol 49 no 9 pp 2157ndash2166 2011

[34] E L M Guimaraes C Empsen A Geerts and L A vanGrunsven ldquoAdvanced glycation end products induce produc-tion of reactive oxygen species via the activation of NADPHoxidase in murine hepatic stellate cellsrdquo Journal of Hepatologyvol 52 no 3 pp 389ndash397 2010

[35] H Mizuguchi T Terao M Kitai et al ldquoInvolvement of pro-tein kinase C120575extracellular signal-regulated kinasepoly(ADP-ribose) polymerase-1 (PARP-1) signaling pathway in histamine-induced up-regulation of histamine H1 receptor gene expres-sion in HeLa cellsrdquo Journal of Biological Chemistry vol 286 no35 pp 30542ndash30551 2011

[36] S Ramakrishna K M Geetha P V V S Bhaskar gopalR P Kumar C P Madav and L Umachandar ldquoEffect ofMallotus PhilippinensisMuell-Arg leaves against hepatotoxicityof Carbon tetrachloride in ratsrdquo International Journal of Phar-maceutical Sciences and Research vol 2 pp 74ndash83 2011

[37] V Sharma ldquoA polyphenolic compound rottlerin demonstratessignificant in vitro cytotoxicity against human cancer celllines isolation and characterization from the fruits ofMallotusphilippinensisrdquo Journal of Plant Biochemistry and Biotechnologyvol 20 no 2 pp 190ndash195 2011

[38] M S Akhtar and I Ahmad ldquoComparative efficacy of Mallotusphilippinensis fruit (Kamala) or Nilzan drug against gastroin-testinal cestodes in Beetal goatsrdquo Small Ruminant Research vol8 no 1-2 pp 121ndash128 1992

[39] A Jabbar M A Raza Z Iqbal and M N Khan ldquoAn inventoryof the ethnobotanicals used as anthelmintics in the southernPunjab (Pakistan)rdquo Journal of Ethnopharmacology vol 108 no1 pp 152ndash154 2006

[40] M Gangwar A Dalai A Chaudhary et al ldquoStudy on activityof alcoholic extract of glands and hairs of fruits of Mallotusphilippinensis in murine cestodal infection modelrdquo Interna-tional Journal of Pharmacy amp Pharmaceutical Sciences vol 4no 1 pp 643ndash645 2012

[41] M Gangwar V C Verma T D Singh S K Singh R KGoel and G Nath ldquoIn-vitro scolicidal activity of Mallotusphilippinensis (Lam) Muell Arg fruit glandular hair extractagainst hydatid cyst Echinococcus granulosusrdquo Asian PacificJournal of Tropical Medicine vol 6 no 8 pp 595ndash601 2013

[42] S S Gupta P Verma and K Hishikar ldquoPurgative andanthelmintic effects of Mallotus philippinensis in rats againsttape wormrdquo Indian Journal of Physiology amp Pharmacology vol28 no 1 pp 63ndash66 1984

[43] A Hussain M N Khan Z Iqbal and M S Sajid ldquoAn accountof the botanical anthelmintics used in traditional veterinarypractices in Sahiwal district of Punjab Pakistanrdquo Journal ofEthnopharmacology vol 119 no 1 pp 185ndash190 2008

[44] Q Hong D E Minter S G Franzblau M Arfan H Amin andM G Reinecke ldquoAnti-tuberculosis compounds from Mallotusphilippinensisrdquo Natural Product Communications vol 5 no 2pp 211ndash217 2010

[45] V K Gupta C Shukla G R S Bisht D Saikia S Kumarand R L Thakur ldquoDetection of anti-tuberculosis activity insome folklore plants by radiometric BACTEC assayrdquo Letters inApplied Microbiology vol 52 no 1 pp 33ndash40 2011

[46] R Tanaka T Nakata C Yamaguchi S Wada T Yamadaand H Tokuda ldquoPotential anti-tumor-promoting activity of3120572-Hydroxy-D a-friedooleanan-2-one from the stem bark ofMallotus philippinensisrdquo Planta Medica vol 74 no 4 pp 413ndash416 2008

[47] A Daikonya S Katsuki J B Wu and S Kitanaka ldquoAnti-allergic agents from natural sources (4) anti-allergic activityof new phloroglucinol derivatives from Mallotus philippinensis(Euphorbiaceae)rdquo Chemical and Pharmaceutical Bulletin vol50 no 12 pp 1566ndash1569 2002

[48] T K Chan S W David C Cheng S P Guan H MKoh and W S Wong ldquoAnti-allergic actions of rottlerin fromMallotus philippinensisis in experimental mast cell-mediatedanaphylactic modelsrdquo Phytomedicine vol 20 no 10 pp 853ndash860 2013

[49] M Khan R A Qureshi M Hussain K Mehmood and R AKhan ldquoHexane soluble extract ofMallotus philippinensis (Lam)Muell Arg root possesses anti-leukaemic activityrdquo ChemistryCentral Journal vol 7 no 1 article 157 2013

[50] R Roshan S G Kulkarni S P Tupe et al ldquoAntifungal dimericchalcone derivative kamalachalcone E from Mallotus philip-pinensisrdquo Natural Product Research Formerly Natural ProductLetters vol 28 no 4 pp 245ndash250 2014

[51] H Nakane M Arisawa A Fujita S Koshimura and KOno ldquoInhibition of HIV-reverse transcriptase activity by somephloroglucinol derivativesrdquo FEBS Letters vol 286 no 1-2 pp83ndash85 1991

[52] T Furumoto N Ozawa Y Inami et al ldquoMallotus philippinensisbark extracts promote preferential migration of mesenchymalstem cells and improve wound healing in micerdquo Phytomedicinevol 21 no 3 pp 247ndash253 2014

[53] Maeda ldquoMethod for producing Mallotus philippinensis dyecomposition and the compositionrdquo US7556829 B2 2009

[54] C Wiart Medicinal Plants of the Asia-Pacific Drugs for theFutureWorld Scientific Singapore 2006

[55] V R Sharma ldquoA review on endangered plant of Mallotusphilippinensis (Lam) MArgrdquo Pharmacologyonline vol 3 pp1256ndash1265 2011

[56] V Tangpu T Temjenmongla and A K Yadav ldquoAnticestodalproperty of Strobilanthes discolor an experimental study inHymenolepis diminutamdashratmodelrdquo Journal of Ethnopharmacol-ogy vol 105 no 3 pp 459ndash463 2006

[57] V Tangpu K Temjenmongla and A K Yadav ldquoAnticestodalactivity ofTrifolium repens extractrdquo Pharmaceutical Biology vol42 no 8 pp 656ndash658 2004

[58] A K Yadav and T Temjenmongla ldquoAnticestodal activity ofHouttuynia cordata leaf extract againstHymenolepis diminuta inexperimentally infected ratsrdquo Journal of Parasitic Diseases vol35 no 2 pp 190ndash194 2011

[59] T Temjenmongla and A K Yadav ldquoAnticestodal efficacy ofLasia spinosa extract against experimental Hymenolepis dimin-uta infections in ratsrdquo Pharmaceutical Biology vol 44 no 7 pp499ndash502 2006

BioMed Research International 13

[60] M L Dhar M M Dhar B N Dhawan B N Mehrotra and CRay ldquoScreening of Indian plants for biological activityrdquo IndianJournal of Experimental Biology vol 6 no 4 pp 232ndash247 1968

[61] Temjenmongla and A K Yadav ldquoAnticestodal efficacy offolklore medicinal plants of Naga tribes in north-east IndiardquoAfrican Journal of Traditional Complementary and AlternativeMedicines vol 2 pp 129ndash133 2005

[62] T V Tangpu and A K Yadav ldquoAnticestodal efficacy of Psidiumguajava against experimental Hymenolepis diminuta infectionin ratsrdquo Indian Journal of Pharmacology vol 38 no 1 pp 29ndash32 2006

[63] R Singh A Mehta P Mehta and K Shukla ldquoAnthelminticactivity of Rhizome extracts of Curcuma longa and Zingiberofficinalerdquo International Journal of Pharmacy and Pharmaceu-tical Sciences vol 3 no 2 pp 236ndash237 2011

[64] M K Asha D Prashanth B Murali R Padmaja and A AmitldquoAnthelmintic activity of essential oil of Ocimum sanctum andeugenolrdquo Fitoterapia vol 72 no 6 pp 669ndash670 2001

[65] J B Githiori J Hoglund P J Waller and R L Baker ldquoTheanthelmintic efficacy of the plantAlbizia anthelmintica againstthe nematode parasites Haemonchus contortus of sheep andHeligmosomoides polygyrus of micerdquo Veterinary Parasitologyvol 116 no 1 pp 23ndash34 2003

[66] N M Enwerema J I Okoguna C O Wambebea D A Oko-rieb and P A Akahc ldquoAnthelmintic activity of the stem barkextracts of Berlina grandiflora and one of its active principlesBetulinic acidrdquo Phytomedicine vol 8 pp 112ndash114 2001

[67] Z Iqbal M Lateef A Jabber M N Ghayur and A HGilani ldquoIn vitro and in vivo anthelmintic activity of Nicotianatabacum L leaves against gastrointestinal nematodes of sheeprdquoPhytotherapy Research vol 20 no 1 pp 46ndash48 2006

[68] Z Iqbal M Lateef A Jabbar G Muhammad and M N KhanldquoAnthelmintic activity of Calotropis procera (Ait) Ait F flowersin sheeprdquo Journal of Ethnopharmacology vol 102 no 2 pp 256ndash261 2005

Submit your manuscripts athttpwwwhindawicom

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MEDIATORSINFLAMMATION

of

Page 7: Mallotus philippinensis Muell. Arg (Euphorbiaceae ...

BioMed Research International 7

M philippinensis

Rottlerin

Fruit

H3C

HO

HO

OH OH

OH

O

O

O

CH3

CH3

CH3

Antifertility

Antimicrobial

Protein inhibition

Antituberculosis activity

Antiallergic activity

Antiproliferative activity

Antiparasitic (cestodal)

Figure 18 Rottlerin and its major biological activities

and metronidazole including Japanese and Pakistani strains[17]

44 Anti-Inflammatory and Immunoregulatory ActivityChalcones derivatives from the fruits of M philippinensisand mallotophilippens C D and E (Figures 12 13 and14) inhibit nitric oxide (NO) production and inducibleNO synthase (iNOS) gene expression by a murinemacrophage-like cell line (RAW 2647) which was activatedby lipopolysaccharide (LPS) and recombinant mouseinterferon-gamma (IFN-gamma) Further investigationssuggest the downregulation of cyclooxygenase-2 geneinterleukin-6 gene and interleukin-1b gene expressionThe above results show that these chalcones have goodanti-inflammatory and immunoregulatory effects [26]

45 Antioxidant Activity and Antiradical Activity Differentfractions of bark and fruit of Mallotus were studied forits total antioxidant activity (TAA) and antiradical activityagainst DPPH on a Sephadex LH-20 column using ethanoland acetone-water asmobile phase Among different extractsbark fraction showed the strongest antiradical activity (TAAvaluemdash527 mmol Trolox equivg) and reducing powerAnother extract that is phenolic fraction shows TAAranging from 058mmol Troloxg (fraction I) to 682mmolTroloxg (fraction IV) this is the strongest fraction showingantiradical activity against DPPH and reducing power TAAof other extracts ranged from 005 to 179mmol Troloxequivg [18 19]

46 Protein Inhibition Implicated in Cancer Processes Proteinkinase is inhibited with some specificity for PKC by rottlerina compound isolated from Mallotus Inhibition of PKCappears due to a strong competition between rottlerin andATP CaM-kinase III is suppressed by rottlerin as effectivelyas PKC 120575 among different protein kinases tested Novelinhibition property and improved selectivity for a distinctPKC isoenzyme of rottlerin are suggestive from its chemicalstructure [27 28] Rottlerin is also very potent in blockingother kinases including AktPKB and p38 MAPK [29ndash31] Italso inhibits human T cell responses [32] reduces MUC5ACexpression in human epithelial cells [33] abrogates reactiveoxygen species production in hepatic stellate cells [34] andprevents histamine-induced H1-receptor gene expression inHeLa cells [35] However still very limited information isavailable of rottlerin towards cancer disease and its mecha-nism of action

47 Hepatoprotective Activity Methanolic extract of Mphilippinensis leaves decreases the CCl

4-induced elevation in

biochemical parameters (SGOT SGPT SALP direct biliru-bin total bilirubin andMDA) on pretreatment at doses 100ndash200mgkg and also reversed the functional and antioxidantparameters This study suggests that leave extract was effec-tive in functional improvement of hepatocytes Histopatho-logical studies also suggest the hepatoprotective activity ofplant [36]

48 In Vitro Cytotoxicity against Human Cancel Cell Glan-dular hair extract of Mallotus fruit powder was assayed

8 BioMed Research International

(a) (b)

(c) (d)

(e)

Figure 19 Mallotus philippinensis (a) Mature plant (b) leaf (c) initial inflorescence of seed setting (d) mature fruits twig (e) mature fruitwith seed

against 14 human cancer cell lines among different fractions95 ethanolic extract showed the highest cytotoxic effect ascompared to 50 ethanolic and aqueous portion Furtherthe chromatographic analysis of the said fraction afforded apolyphenolic molecule rottlerin inMallotus plant [37]

49 Anticestodal ActivityVeterinary Applications M philip-pinensis fruit was found to be very effective against gas-trointestinal cestodes in Beetal goats and other ruminantsComparative anticestodal efficacies of single oral dose treat-ments with the powdered fruit ofM philippinensis (125 250and 375mgkg) its water or methanol extracts (equivalent to375mgkg) and the total glycosides (25 50 and 100mgkg)were determined in naturally cestode-infected Beetal goats[38] An ethnobotanical survey has been conducted foranthelmintics in ruminants so as to document the plantsused to treat and control helminthes Mallotus has beenfrequently used to treat helminthosis in ruminants [39] M

philippinensis fruit extract of 800mgkg twice daily for 3days was observed to have curative efficacy against matureadult worms of Hymenolepis diminuta The total follow-upperiod of 90 days did not show any further excretion of eggsin the faeces of treated rats Praziquantel at the dosage of5mgkg also produced a similar effect [40] In vitro scolicidalactivity ofM philippinensis (Lam)Muell Arg fruit glandularhair extract against hydatid cyst Echinococcus granulosusprotoscoleces at concentrations 10 and 20mgmL shows themortality rate 97 to 99 respectively for 60min treatmentwhile up to 93 mortality was observed with 20mgmLfor only 10min treatment This proves that the extract hassignificant scolicidal activity with almost no associated sideeffects [41] In vivo animal model experiment will be furtherrequired to prove its effect against Hydatid cyst

410 Purgative Activity and Anthelmintic Activity A signifi-cant purgative effect after an oral dose (120mgkg) in rats was

BioMed Research International 9

assessed from resins isolated from plant Its effect was evalu-ated from the weight of faeces as well as from surface areaof blotting paper soaked by liquid faeces The anthelminticeffect on tape worm was evaluated in albino rates fromthe resin of the plant showed lethal effect of 3569 and7821 respectively in small intestine in concentrations 60and 120mgkg respectively [42 43]

411 Antituberculosis Activity Organic extract of plant afterbioassay-directed fractionation yields five compounds themost active of which againstMycobacterium tuberculosis wasa new compound 8-cinnamoyl-57-dihydroxy-22-dimethyl-6-geranylchromene for which the name mallotophilippenF is suggested The second compound 8-cinnamoyl-22-dimethyl-7-hydroxy-5-methoxychromene was isolated froma natural source for the first time while the remaining threecompounds rottlerin isoallorottlerin or isorottlerin andthe so-called ldquored compoundrdquo 8-cinnamoyl-57-dihydroxy-226-trimethylchromene had been already isolated fromthis plant Isolated compounds were identified by 2D-NMRand C-13 NMR [44] Ethanolic extract of plant was assayedfor antimycobacterial activity against M smegmatis by discdiffusion assay Further antituberculosis potential of leavesextract was identified by radiometric BACTEC assay resultrevealed that ethanolic extract ofM philippensis showed anti-tuberculosis activity against virulent and avirulent strains ofM tuberculosis H37Rv andM tuberculosis H37Ra with min-imum inhibitory concentrations of 025 and 0125mgmLminus1respectively The inhibition in growth index values of Mtuberculosis was observed in the presence of ethyl acetatefraction at a minimum concentration of 005mgmLminus1 Itsuggests that ethanolic and ethyl acetate fraction of plantpossesses significant antimycobacterial activity [45] Steambark of M philippinensis has also been reported for itsantitumor promoting effect which was due to the presenceof 3120572-Hydroxy-DA-friedooleanan-2-one [46]

412 Antiallergic Activity M philippinensis fruit containstwo new phloroglucinol derivatives mallotophilippensA and B (Figures 10 and 11) which were identified usingchemical and spectral data as 1-[57-dihydroxy-22-di-methyl-6-(246-trihydroxy-3-isobutyryl-5-methyl-benzyl)-2H-chromen-8-yl]-2-methyl-butan-1-one and 1-[6-(3-Acetyl-246-trihydroxy-5-methyl-benzyl)-57-dihydroxy-22-dim-ethyl-2H-chromen-8-yl]-2-methyl-butan-1-one respe-ctively These compounds inhibited the production ofnitric oxide (NO) and inducible NO synthase (iNOS) geneexpression by a murine macrophage-like cell line (RAW2647) which was activated by lipopolysaccharide (LPS)and recombinant mouse interferon-g (IFN-g) Furtherphloroglucinol derivatives inhibit histamine release from ratperitoneal mast cells induced by compound 4880This studysuggests its anti-inflammatory activity [47] Rottlerin hasbeen tested in animal models of IgE-dependent anaphylaxisand the antiallergic mechanisms of action in mast cellsAntiallergic action of rottlerin has been tested in passivecutaneous anaphylaxis and passive systemic anaphylaxismouse models and in anaphylactic contraction of bronchial

rings isolated from sensitized guinea pigs This experimentsproves antiallergic effect of rottlerin by blocking IgE-inducedmast cell degranulation This report suggests the use ofrottlerin in mast cell-mediated allergic disorders includingurticaria and allergic asthma [48]

413 Anti-Leukaemic Activity Root extract ofM philippinen-sis was tested on human promyelocytic leukemia HL-60 cellproliferation cell cycle regulators and apoptosis in order toinvestigate its antileukemic effect Hexane fraction showedpromising toxicity against p53-deficient HL-60 cells (IC

50

15mg dry roots equivalentmL medium) after 72 h andinterestingly inhibition of cell proliferation was preceded bythe upregulation of the protooncogenes Cdc25A and cyclinD1 within 24 hours suggesting its antileukemic effect inHL-60 cells After isolation and identification by GC-MSpolyphenols were the main compounds of the hexane extractthat inhibited proliferation and induced apoptosis [49]

414 Antiproliferative Activity Antiproliferative effect wasevaluated against Thp-1 cell lines from the isolated com-pounds of M philippinensis fruit extract in which 41015840-hydroxyrottlerin showed 54 growth inhibition ofThp-1 cellline [50] Other isolated compounds were also tested againstdifferent fungi andwere found to be very effective IC

50values

415 Anti-HIV Activity Four phloroglucinol derivativesnamed mallotophenone (5-methylene-bis-26-dihydroxy-3-methyl-4-methoxyacetophenone) mallotochromene (8-acetyl-57-dihydroxy-6-(3-acetyl-24-dihydroxy-5-methyl-6-methoxybenzyl)-22-dimethylchromene) mallotojaponin(3-(33(dimethylallyl) S-(3(acetyl-24-dihydroxy-5-methyl-6-methoxybenzyl)-phloracetophenone) andmallotolerin (3-(3-methyl-2-hydroxybut-3-enyl)-5-(3-acetyl-24-dihydroxy-5-methyl-6-methoxybenzyl)-phloracetophenone) weretested for their ability to inhibit the activity of humanimmunodeficiency virus- (HIV-) reverse transcriptaseThe mode of inhibition of mallotojaponin was foundto be competitive with respect to the template primer(rA)n (dT)12ndash18 and noncompetitive with respect to thetriphosphate substrate dTTPThe Ki value of mallotojaponinfor HIV-reverse transcriptase was determined to be 61 120583M[51]

416 Antitumor Activity Four known friedelane-type trit-erpenoids friedelin 3-hydroxy-DA-friedoolean-3-en-2-one 2120573-hydroxy-DA-friedooleanan-3-one and 3120572-hy-droxy-DA-friedooleanan-2-one and two known lupane-type triterpenoids lupeol and betulin were isolated fromthe stem bark of M philippinensis and were tested fortheir inhibitory effects on Epstein-Barr virus early antigen(EBV-EA) activation induced by 12-O-tetradecanoylphorbol13-acetate (TPA) The inhibitory effect of compounds 2(IC50

= 292mol ratio32 pmolTPA) and 4 (IC50

= 288) wasstronger than those of the other compounds tested and thepositive control curcumin (IC

50= 343) Compound 3120572-

hydroxy-DA-friedooleanan-2-one strongly inhibited mouse

10 BioMed Research International

skin tumor promotion in an in vivo two-stage carcinogenesismodel [46]

417 Wound Healing and Mesenchymal Stem Cell (MSC)Proliferation Bark extract ofMallotus philippinensis has beentested in vitro for wound healing activity by examining theproliferation and migration of MSCs KUM6 cells prolifer-ation and migration have been enhanced at 016ndash4 120583gmLand unregulated the activity of MSCs by secreting variouscytokines to wounded site from bone marrow to systemiccirculation and finally remodel wounded tissues [52]

418 Toxicities Seeds of M philippinensis ethereal extracthave adverse effect on various parameters of female rats Eventhe extract reduces serum levels of gonadotropins in treatedanimals at high dose of 100mgkg body weight Reducedweights of ovary and uterus follicular development andincreased atretic follicular in the ovary are due to subnormallevels of steroid hormones Thus pregnancy is very difficultin female rats treated with kamala seed extract [22]

419 Colouring Agent-Dye Glandular hairs of fruit aremostly used as an orange dye for silk [53 54]

5 Pharmacognostic Evaluation ofMallotus philippinensis

Morphological study shows that fruit depresses globoseand is three-lobed capsule 5ndash7mm times 8ndash10ndash12mm stellate-puberulose and with abundant orange or reddish glan-dular granules Seeds are subglobose and black in colorOrganoleptic property of the red fruit shows that it is tastelessand odourless Microscopic description showed the presenceof epicarp which contained a compactly packed layer ofmucilaginous cells and mesocarp composed of columnarcells which are closely arranged Its polygonal cells are com-pactly arranged in 2-3 layers Presence of lignified vasculararrangement has been observed in the transverse section [55]

6 Conclusion and Future Perspective

Medicinal plants have been clinically used and its interest hasbeen dramatically increased over the past decades throughoutthe world and its formulations are increasingly cited inmedia Daily consumption of the natural products and theirformulations by an extensive number of patients lead toserious concern for scientist to study its efficacy and safetyBecause of extensive use and its benefits natural productsin many countries are regulated both as medicinal productsand as food supplements often labeled as natural foodsupplements

Traditional use and its growing demand for Mallotusphilippinensis and its other species lead to compile this reviewand commented on the current knowledge provided byclinical and preclinical research on the effect of this plant

Mallotus philippinensis has been widely used as tradi-tional medicine in several parts of countries including IndiaEvery part of this plant possesses its specific medicinal prop-erties and is usedmainly in ayurveda to fight against intestinalworms in domestic and grazing animals when administeredwith jaggeryHowever only a few reports are attributed to thisplant and its different parts and there is a large scope for inves-tigation Hence it is required to explore more of its potentialwithin the field of medicinal and pharmaceutical sciences fornovel and fruitful application of this plant in form of naturalformulation Along with this medicinal importance thisplant is used against human pathogens including H pylorianti-inflammatory activity antioxidant antiradical proteininhibition hepatoprotective antiallergic anti-HIV activityand many more Phytochemical investigation revealed that alarge number phenol derivatives and several miscellaneouscompounds from different classes have been isolated fromthis species The phenols diterpenoids steroids flavonoidscardenolides triterpenoids coumarins and isocoumarinsare mostly distributed in all parts of the plant The othermajor isolated pure compounds from this species mostlybelong to phenolic group exhibiting most of the biologicalactivity Various types of extracts from different parts andsingle compounds derived from this species have beenfound to possess biological activities including antioxidantantimicrobial anti-inflammatory cytotoxicity and immunemodulatory Fruit and bark of plant contain condensed tan-nins responsible for antioxidant activity Somenovel chalconederivatives mallotophilippens C D and E were isolatedfrom the fruits of M philippinensis Mallotoxin or rottlerinhas great anticancerous potential Among the ever-anticanceragents rottlerin appears to have great potentiality for beingused in chemotherapy Rottlerin will become a potentialmolecule for research in future to treat cancerous cell as itwill affect cell machineries involved in apoptosis survivaland autophage This suggests the view that this species haspotential to be a beneficial chemotherapeutic remedy

Although the data and other reports provided that thismedicinal plant is of great biological use in different phar-macological activities including anticancer further researchis needed in different areas regarding the toxicity and efficacyof pure phytochemicals isolated from different parts of thisplant More data will be needed from preclinical and clinicalstudies on humans to clarify its potency and safety aslack of knowledge with respect to its adverse effects andmethodological accuracy in the literature limits towardsits standardized formulation Furthermore the mechanismof action of the phytochemicals and extract of Mallotusphilippinensis is unclear more exhaustive studies will beperformed to explore its mechanism and structure activityrelationship among various constituents

In conclusion this review confirms the great potential ofMallotus philippinensis As very limited information is stillknown for this species it leads us to continue the study ondifferent species of Mallotus plant and its interesting phar-macological properties Further natural product chemistryof isolated moiety and its structural analysis of compounds

BioMed Research International 11

responsible for these activities will be an interesting field ofresearch

Conflict of Interests

The authors declare that there is no conflict of interests re-garding the publication of this paper

Acknowledgment

The authors gratefully acknowledge the financial supportprovided by CSIR Government of India New Delhi forawarding SRF in the form of research fellowship

References

[1] C-J Widen and H S Puri ldquoNatural occurrence and chemicalvariability of phloroglucinols inKamalardquoPlantaMedica vol 40no 3 pp 284ndash287 1980

[2] R Singh K C Singhal and N U Khan ldquoAntifilarial activity ofMallotus philippinensisLam on Setaria cervie (Nematoda Filar-ioidea) in-vitrordquo Indian Journal of Physiology andPharmacologyvol 41 no 4 pp 397ndash403 1997

[3] V P Kumar N S Chauhan H Padh and M Rajani ldquoSearchfor antibacterial and antifungal agents from selected Indianmedicinal plantsrdquo Journal of Ethnopharmacology vol 107 no2 pp 182ndash188 2006

[4] S Shrikumar and T K Ravi ldquoApproaches towards developmentand promotion of herbal drugsrdquo Pharmaceutical Reviews vol 1no 1 pp 180ndash183 2007

[5] C Orwa A Mutua and R Kindt ldquoAgroforestree Database atree reference and selection guiderdquo Version 4 0 2009

[6] K Usmanghani A Saeed and M T Alam ldquoIndusynicMedicine Karachirdquo Research Institute of Indusyunic Medicinevol 1997 pp 285ndash287 1997

[7] F Ahmad and S Hashmi ldquoAdulteration in commercial Kamila(Mallotus philippinensisMuell) an anthelmintic drug of reputerdquoHamdard Medicus vol 38 pp 62ndash67 1995

[8] K D Roberts E Weiss and T Reichstein ldquoGlycosides andaglycons CCLII Cardenolides of the seed of Mallotus philip-pinensisrdquo Helvetica Chimica Acta vol 46 pp 2886ndash2893 1963

[9] M Bandopadhyay V K Dhingra and S K Mukerjee ldquoTriter-penoid and other components of Mallotus philippinensisrdquo Phy-tochemistry vol 11 no 4 p 1511 1972

[10] S P Nair and J Madhusudana Rao ldquoKamaladiol-3-acetate fromthe stem bark of Mallotus philippinensisrdquo Phytochemistry vol32 pp 407ndash409 1993

[11] J DWansi JWandjiW A Kamdem et al ldquoTriterpenoids fromDrypetes chevalieri Beille (Euphorbiaceae)rdquo Natural ProductResearch vol 20 no 6 pp 586ndash592 2006

[12] P Castenada A Bahena and E Garcia ldquoChemical studieson Mexican plants used in traditional medicine XXIX Sec-ondary metabolites from the stem bark of Celaeno-dendronmexicanumrdquo Journal of Natural Products vol 56 pp 1575ndash15791993

[13] T Tanaka T Ito M Iinuma Y Takahashi and H NaganawaldquoDimeric chalcone derivatives from Mallotus philippinensisrdquoPhytochemistry vol 48 no 8 pp 1423ndash1427 1998

[14] T M Nguyen V M Chau V K Phan et al ldquoStudy on chemicalconstituents of the leaves of Mallotus philippinensisrdquo Tap ChiHoa Hoc vol 48 pp 352ndash357 2010

[15] M Furusawa Y Ido T Tanaka et al ldquoNovel complex flavonoidsfrom Mallotus philippinensis (Kamala tree)rdquo Helvetica ChimicaActa vol 88 no 5 pp 1048ndash1058 2005

[16] M Lounasmaa C J Widen C M Tuuf and A HuhtikangasldquoOn the phloroglucinol derivatives of Mallotus philippinensisrdquoPlanta Medica vol 28 no 1 pp 16ndash31 1975

[17] S F H Zaidi I Yoshida F Butt et al ldquoPotent bactericidal con-stituents from Mallotus philippinensis against clarithromycinand metronidazole resistant strains of Japanese and Pakistanihelicobacter pylorirdquo Biological and Pharmaceutical Bulletin vol32 no 4 pp 631ndash636 2009

[18] M Arfan H Amin M Karamac et al ldquoAntioxidant activityof extracts of Mallotus philippinensis fruit and barkrdquo Journal ofFood Lipids vol 14 no 3 pp 280ndash297 2007

[19] M Arfan K Hazrat and K Magdalena ldquoAntioxidant activityof phenolic fractions of Mallotus philippinensis bark extractrdquoJournal of Food Science vol 27 no 2 pp 109ndash117 2009

[20] R Saijo G Nonaka and I Nishioka ldquoTannins and related com-pounds LXXXVIII Isolation and characterization of hydrolyz-able tannins fromMallotus japonicus (Thunb)Mueller-Arg andM philippinensis (Lam)Mueller-ArgrdquoChemical amp Pharmaceu-tical Bulletin vol 37 no 11 pp 2940ndash2947 1989

[21] S C Gupta S S Gupta and J S Aggarwal ldquoChemical exami-nation of the seeds of Mallotus philippinensis III Constitutionof kamlolenic acid isolated from the oilrdquo Journal of Scientific ampIndustrial Research vol 12 pp 240ndash242 1953

[22] S C Thakur S S Thakur S K Chaube and S P Singh ldquoAnetheral extract of Kamala (Mallotus philippinensis (Moll Arg)Lam) seed induce adverse effects on reproductive parametersof female ratsrdquo Reproductive Toxicology vol 20 no 1 pp 149ndash156 2005

[23] M L Gujral D R Varma K N Sareen and A K Roy ldquoOralcontraceptives II Antifertility effect ofMallotus philippinensisrdquoIndian Journal of Medical Research vol 48 pp 52ndash58 1960

[24] KMoorthy K Srinivasan C Subramanian CMohanasundariand M Palaniswamy ldquoPhyto-chemical screening and antibac-terial evaluation of stem bark of Mallotus philippinensis varTomentosusrdquoAfrican Journal of Biotechnology vol 6 no 13 pp1521ndash1523 2007

[25] M Gangwar D Kumar R Tilak et al ldquoQualitative phy-tochemical characterization and antibacterial evaluation ofglandular hairs ofMallotus philippinensis fruit extractrdquo Journalof Pharmacy Research vol 4 no 11 pp 4214ndash4216 2011

[26] A Daikonya S Katsuki and S Kitanaka ldquoAntiallergic agentsfrom naturalsources 9 Inhibition of nitric oxide productionby novel chalcone derivatives from Mallotus philippinensis(Euphorbiaceae)rdquo Chemical amp Pharmaceutical Bulletin vol 52no 11 pp 1326ndash1329 2004

[27] M Gschwendt H J Muller K Kielbassa et al ldquoRottlerina novel protein kinase inhibitorrdquo Biochemical and BiophysicalResearch Communications vol 199 no 1 pp 93ndash98 1994

[28] Y F Liao Y C Hung W H Chang et al ldquoThe PKC deltainhibitor rottlerin induces apoptosis of haematopoietic celllines through mitochondrial membrane depolarization andcaspasescascaderdquo Life Sciences vol 77 no 6 pp 707ndash719 2005

[29] H S Kang E K Park K H Kim et al ldquoReceptor activatorof nuclear factor-kappa B is induced by a rottlerin-sensitiveand p38 MAP kinase-dependent pathway during monocytedifferentiationrdquoMolecules and Cells vol 17 no 3 pp 438ndash4452004

12 BioMed Research International

[30] S P Soltoff ldquoRottlerin an inappropriate and ineffectiveinhibitor of PKC120575rdquo Trends in Pharmacological Sciences vol 28no 9 pp 453ndash458 2007

[31] Y Choi D K Kim S S Kang J K Sonn and E J Jin ldquoIntegrinsignaling and cell spreading alterations by rottlerin treatment ofchick limb bud mesenchymal cellsrdquo Biochimie vol 91 no 5 pp624ndash631 2009

[32] C Springael S Thomas S Rahmouni et al ldquoRottlerin inhibitshuman T cell responsesrdquo Biochemical Pharmacology vol 73 no4 pp 515ndash525 2007

[33] J H Choi Y P Hwang E H Han et al ldquoInhibition of acrolein-stimulated MUC5AC expression by Platycodon grandiflorumroot-derived saponin in A549 cellsrdquo Food and Chemical Toxi-cology vol 49 no 9 pp 2157ndash2166 2011

[34] E L M Guimaraes C Empsen A Geerts and L A vanGrunsven ldquoAdvanced glycation end products induce produc-tion of reactive oxygen species via the activation of NADPHoxidase in murine hepatic stellate cellsrdquo Journal of Hepatologyvol 52 no 3 pp 389ndash397 2010

[35] H Mizuguchi T Terao M Kitai et al ldquoInvolvement of pro-tein kinase C120575extracellular signal-regulated kinasepoly(ADP-ribose) polymerase-1 (PARP-1) signaling pathway in histamine-induced up-regulation of histamine H1 receptor gene expres-sion in HeLa cellsrdquo Journal of Biological Chemistry vol 286 no35 pp 30542ndash30551 2011

[36] S Ramakrishna K M Geetha P V V S Bhaskar gopalR P Kumar C P Madav and L Umachandar ldquoEffect ofMallotus PhilippinensisMuell-Arg leaves against hepatotoxicityof Carbon tetrachloride in ratsrdquo International Journal of Phar-maceutical Sciences and Research vol 2 pp 74ndash83 2011

[37] V Sharma ldquoA polyphenolic compound rottlerin demonstratessignificant in vitro cytotoxicity against human cancer celllines isolation and characterization from the fruits ofMallotusphilippinensisrdquo Journal of Plant Biochemistry and Biotechnologyvol 20 no 2 pp 190ndash195 2011

[38] M S Akhtar and I Ahmad ldquoComparative efficacy of Mallotusphilippinensis fruit (Kamala) or Nilzan drug against gastroin-testinal cestodes in Beetal goatsrdquo Small Ruminant Research vol8 no 1-2 pp 121ndash128 1992

[39] A Jabbar M A Raza Z Iqbal and M N Khan ldquoAn inventoryof the ethnobotanicals used as anthelmintics in the southernPunjab (Pakistan)rdquo Journal of Ethnopharmacology vol 108 no1 pp 152ndash154 2006

[40] M Gangwar A Dalai A Chaudhary et al ldquoStudy on activityof alcoholic extract of glands and hairs of fruits of Mallotusphilippinensis in murine cestodal infection modelrdquo Interna-tional Journal of Pharmacy amp Pharmaceutical Sciences vol 4no 1 pp 643ndash645 2012

[41] M Gangwar V C Verma T D Singh S K Singh R KGoel and G Nath ldquoIn-vitro scolicidal activity of Mallotusphilippinensis (Lam) Muell Arg fruit glandular hair extractagainst hydatid cyst Echinococcus granulosusrdquo Asian PacificJournal of Tropical Medicine vol 6 no 8 pp 595ndash601 2013

[42] S S Gupta P Verma and K Hishikar ldquoPurgative andanthelmintic effects of Mallotus philippinensis in rats againsttape wormrdquo Indian Journal of Physiology amp Pharmacology vol28 no 1 pp 63ndash66 1984

[43] A Hussain M N Khan Z Iqbal and M S Sajid ldquoAn accountof the botanical anthelmintics used in traditional veterinarypractices in Sahiwal district of Punjab Pakistanrdquo Journal ofEthnopharmacology vol 119 no 1 pp 185ndash190 2008

[44] Q Hong D E Minter S G Franzblau M Arfan H Amin andM G Reinecke ldquoAnti-tuberculosis compounds from Mallotusphilippinensisrdquo Natural Product Communications vol 5 no 2pp 211ndash217 2010

[45] V K Gupta C Shukla G R S Bisht D Saikia S Kumarand R L Thakur ldquoDetection of anti-tuberculosis activity insome folklore plants by radiometric BACTEC assayrdquo Letters inApplied Microbiology vol 52 no 1 pp 33ndash40 2011

[46] R Tanaka T Nakata C Yamaguchi S Wada T Yamadaand H Tokuda ldquoPotential anti-tumor-promoting activity of3120572-Hydroxy-D a-friedooleanan-2-one from the stem bark ofMallotus philippinensisrdquo Planta Medica vol 74 no 4 pp 413ndash416 2008

[47] A Daikonya S Katsuki J B Wu and S Kitanaka ldquoAnti-allergic agents from natural sources (4) anti-allergic activityof new phloroglucinol derivatives from Mallotus philippinensis(Euphorbiaceae)rdquo Chemical and Pharmaceutical Bulletin vol50 no 12 pp 1566ndash1569 2002

[48] T K Chan S W David C Cheng S P Guan H MKoh and W S Wong ldquoAnti-allergic actions of rottlerin fromMallotus philippinensisis in experimental mast cell-mediatedanaphylactic modelsrdquo Phytomedicine vol 20 no 10 pp 853ndash860 2013

[49] M Khan R A Qureshi M Hussain K Mehmood and R AKhan ldquoHexane soluble extract ofMallotus philippinensis (Lam)Muell Arg root possesses anti-leukaemic activityrdquo ChemistryCentral Journal vol 7 no 1 article 157 2013

[50] R Roshan S G Kulkarni S P Tupe et al ldquoAntifungal dimericchalcone derivative kamalachalcone E from Mallotus philip-pinensisrdquo Natural Product Research Formerly Natural ProductLetters vol 28 no 4 pp 245ndash250 2014

[51] H Nakane M Arisawa A Fujita S Koshimura and KOno ldquoInhibition of HIV-reverse transcriptase activity by somephloroglucinol derivativesrdquo FEBS Letters vol 286 no 1-2 pp83ndash85 1991

[52] T Furumoto N Ozawa Y Inami et al ldquoMallotus philippinensisbark extracts promote preferential migration of mesenchymalstem cells and improve wound healing in micerdquo Phytomedicinevol 21 no 3 pp 247ndash253 2014

[53] Maeda ldquoMethod for producing Mallotus philippinensis dyecomposition and the compositionrdquo US7556829 B2 2009

[54] C Wiart Medicinal Plants of the Asia-Pacific Drugs for theFutureWorld Scientific Singapore 2006

[55] V R Sharma ldquoA review on endangered plant of Mallotusphilippinensis (Lam) MArgrdquo Pharmacologyonline vol 3 pp1256ndash1265 2011

[56] V Tangpu T Temjenmongla and A K Yadav ldquoAnticestodalproperty of Strobilanthes discolor an experimental study inHymenolepis diminutamdashratmodelrdquo Journal of Ethnopharmacol-ogy vol 105 no 3 pp 459ndash463 2006

[57] V Tangpu K Temjenmongla and A K Yadav ldquoAnticestodalactivity ofTrifolium repens extractrdquo Pharmaceutical Biology vol42 no 8 pp 656ndash658 2004

[58] A K Yadav and T Temjenmongla ldquoAnticestodal activity ofHouttuynia cordata leaf extract againstHymenolepis diminuta inexperimentally infected ratsrdquo Journal of Parasitic Diseases vol35 no 2 pp 190ndash194 2011

[59] T Temjenmongla and A K Yadav ldquoAnticestodal efficacy ofLasia spinosa extract against experimental Hymenolepis dimin-uta infections in ratsrdquo Pharmaceutical Biology vol 44 no 7 pp499ndash502 2006

BioMed Research International 13

[60] M L Dhar M M Dhar B N Dhawan B N Mehrotra and CRay ldquoScreening of Indian plants for biological activityrdquo IndianJournal of Experimental Biology vol 6 no 4 pp 232ndash247 1968

[61] Temjenmongla and A K Yadav ldquoAnticestodal efficacy offolklore medicinal plants of Naga tribes in north-east IndiardquoAfrican Journal of Traditional Complementary and AlternativeMedicines vol 2 pp 129ndash133 2005

[62] T V Tangpu and A K Yadav ldquoAnticestodal efficacy of Psidiumguajava against experimental Hymenolepis diminuta infectionin ratsrdquo Indian Journal of Pharmacology vol 38 no 1 pp 29ndash32 2006

[63] R Singh A Mehta P Mehta and K Shukla ldquoAnthelminticactivity of Rhizome extracts of Curcuma longa and Zingiberofficinalerdquo International Journal of Pharmacy and Pharmaceu-tical Sciences vol 3 no 2 pp 236ndash237 2011

[64] M K Asha D Prashanth B Murali R Padmaja and A AmitldquoAnthelmintic activity of essential oil of Ocimum sanctum andeugenolrdquo Fitoterapia vol 72 no 6 pp 669ndash670 2001

[65] J B Githiori J Hoglund P J Waller and R L Baker ldquoTheanthelmintic efficacy of the plantAlbizia anthelmintica againstthe nematode parasites Haemonchus contortus of sheep andHeligmosomoides polygyrus of micerdquo Veterinary Parasitologyvol 116 no 1 pp 23ndash34 2003

[66] N M Enwerema J I Okoguna C O Wambebea D A Oko-rieb and P A Akahc ldquoAnthelmintic activity of the stem barkextracts of Berlina grandiflora and one of its active principlesBetulinic acidrdquo Phytomedicine vol 8 pp 112ndash114 2001

[67] Z Iqbal M Lateef A Jabber M N Ghayur and A HGilani ldquoIn vitro and in vivo anthelmintic activity of Nicotianatabacum L leaves against gastrointestinal nematodes of sheeprdquoPhytotherapy Research vol 20 no 1 pp 46ndash48 2006

[68] Z Iqbal M Lateef A Jabbar G Muhammad and M N KhanldquoAnthelmintic activity of Calotropis procera (Ait) Ait F flowersin sheeprdquo Journal of Ethnopharmacology vol 102 no 2 pp 256ndash261 2005

Submit your manuscripts athttpwwwhindawicom

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MEDIATORSINFLAMMATION

of

Page 8: Mallotus philippinensis Muell. Arg (Euphorbiaceae ...

8 BioMed Research International

(a) (b)

(c) (d)

(e)

Figure 19 Mallotus philippinensis (a) Mature plant (b) leaf (c) initial inflorescence of seed setting (d) mature fruits twig (e) mature fruitwith seed

against 14 human cancer cell lines among different fractions95 ethanolic extract showed the highest cytotoxic effect ascompared to 50 ethanolic and aqueous portion Furtherthe chromatographic analysis of the said fraction afforded apolyphenolic molecule rottlerin inMallotus plant [37]

49 Anticestodal ActivityVeterinary Applications M philip-pinensis fruit was found to be very effective against gas-trointestinal cestodes in Beetal goats and other ruminantsComparative anticestodal efficacies of single oral dose treat-ments with the powdered fruit ofM philippinensis (125 250and 375mgkg) its water or methanol extracts (equivalent to375mgkg) and the total glycosides (25 50 and 100mgkg)were determined in naturally cestode-infected Beetal goats[38] An ethnobotanical survey has been conducted foranthelmintics in ruminants so as to document the plantsused to treat and control helminthes Mallotus has beenfrequently used to treat helminthosis in ruminants [39] M

philippinensis fruit extract of 800mgkg twice daily for 3days was observed to have curative efficacy against matureadult worms of Hymenolepis diminuta The total follow-upperiod of 90 days did not show any further excretion of eggsin the faeces of treated rats Praziquantel at the dosage of5mgkg also produced a similar effect [40] In vitro scolicidalactivity ofM philippinensis (Lam)Muell Arg fruit glandularhair extract against hydatid cyst Echinococcus granulosusprotoscoleces at concentrations 10 and 20mgmL shows themortality rate 97 to 99 respectively for 60min treatmentwhile up to 93 mortality was observed with 20mgmLfor only 10min treatment This proves that the extract hassignificant scolicidal activity with almost no associated sideeffects [41] In vivo animal model experiment will be furtherrequired to prove its effect against Hydatid cyst

410 Purgative Activity and Anthelmintic Activity A signifi-cant purgative effect after an oral dose (120mgkg) in rats was

BioMed Research International 9

assessed from resins isolated from plant Its effect was evalu-ated from the weight of faeces as well as from surface areaof blotting paper soaked by liquid faeces The anthelminticeffect on tape worm was evaluated in albino rates fromthe resin of the plant showed lethal effect of 3569 and7821 respectively in small intestine in concentrations 60and 120mgkg respectively [42 43]

411 Antituberculosis Activity Organic extract of plant afterbioassay-directed fractionation yields five compounds themost active of which againstMycobacterium tuberculosis wasa new compound 8-cinnamoyl-57-dihydroxy-22-dimethyl-6-geranylchromene for which the name mallotophilippenF is suggested The second compound 8-cinnamoyl-22-dimethyl-7-hydroxy-5-methoxychromene was isolated froma natural source for the first time while the remaining threecompounds rottlerin isoallorottlerin or isorottlerin andthe so-called ldquored compoundrdquo 8-cinnamoyl-57-dihydroxy-226-trimethylchromene had been already isolated fromthis plant Isolated compounds were identified by 2D-NMRand C-13 NMR [44] Ethanolic extract of plant was assayedfor antimycobacterial activity against M smegmatis by discdiffusion assay Further antituberculosis potential of leavesextract was identified by radiometric BACTEC assay resultrevealed that ethanolic extract ofM philippensis showed anti-tuberculosis activity against virulent and avirulent strains ofM tuberculosis H37Rv andM tuberculosis H37Ra with min-imum inhibitory concentrations of 025 and 0125mgmLminus1respectively The inhibition in growth index values of Mtuberculosis was observed in the presence of ethyl acetatefraction at a minimum concentration of 005mgmLminus1 Itsuggests that ethanolic and ethyl acetate fraction of plantpossesses significant antimycobacterial activity [45] Steambark of M philippinensis has also been reported for itsantitumor promoting effect which was due to the presenceof 3120572-Hydroxy-DA-friedooleanan-2-one [46]

412 Antiallergic Activity M philippinensis fruit containstwo new phloroglucinol derivatives mallotophilippensA and B (Figures 10 and 11) which were identified usingchemical and spectral data as 1-[57-dihydroxy-22-di-methyl-6-(246-trihydroxy-3-isobutyryl-5-methyl-benzyl)-2H-chromen-8-yl]-2-methyl-butan-1-one and 1-[6-(3-Acetyl-246-trihydroxy-5-methyl-benzyl)-57-dihydroxy-22-dim-ethyl-2H-chromen-8-yl]-2-methyl-butan-1-one respe-ctively These compounds inhibited the production ofnitric oxide (NO) and inducible NO synthase (iNOS) geneexpression by a murine macrophage-like cell line (RAW2647) which was activated by lipopolysaccharide (LPS)and recombinant mouse interferon-g (IFN-g) Furtherphloroglucinol derivatives inhibit histamine release from ratperitoneal mast cells induced by compound 4880This studysuggests its anti-inflammatory activity [47] Rottlerin hasbeen tested in animal models of IgE-dependent anaphylaxisand the antiallergic mechanisms of action in mast cellsAntiallergic action of rottlerin has been tested in passivecutaneous anaphylaxis and passive systemic anaphylaxismouse models and in anaphylactic contraction of bronchial

rings isolated from sensitized guinea pigs This experimentsproves antiallergic effect of rottlerin by blocking IgE-inducedmast cell degranulation This report suggests the use ofrottlerin in mast cell-mediated allergic disorders includingurticaria and allergic asthma [48]

413 Anti-Leukaemic Activity Root extract ofM philippinen-sis was tested on human promyelocytic leukemia HL-60 cellproliferation cell cycle regulators and apoptosis in order toinvestigate its antileukemic effect Hexane fraction showedpromising toxicity against p53-deficient HL-60 cells (IC

50

15mg dry roots equivalentmL medium) after 72 h andinterestingly inhibition of cell proliferation was preceded bythe upregulation of the protooncogenes Cdc25A and cyclinD1 within 24 hours suggesting its antileukemic effect inHL-60 cells After isolation and identification by GC-MSpolyphenols were the main compounds of the hexane extractthat inhibited proliferation and induced apoptosis [49]

414 Antiproliferative Activity Antiproliferative effect wasevaluated against Thp-1 cell lines from the isolated com-pounds of M philippinensis fruit extract in which 41015840-hydroxyrottlerin showed 54 growth inhibition ofThp-1 cellline [50] Other isolated compounds were also tested againstdifferent fungi andwere found to be very effective IC

50values

415 Anti-HIV Activity Four phloroglucinol derivativesnamed mallotophenone (5-methylene-bis-26-dihydroxy-3-methyl-4-methoxyacetophenone) mallotochromene (8-acetyl-57-dihydroxy-6-(3-acetyl-24-dihydroxy-5-methyl-6-methoxybenzyl)-22-dimethylchromene) mallotojaponin(3-(33(dimethylallyl) S-(3(acetyl-24-dihydroxy-5-methyl-6-methoxybenzyl)-phloracetophenone) andmallotolerin (3-(3-methyl-2-hydroxybut-3-enyl)-5-(3-acetyl-24-dihydroxy-5-methyl-6-methoxybenzyl)-phloracetophenone) weretested for their ability to inhibit the activity of humanimmunodeficiency virus- (HIV-) reverse transcriptaseThe mode of inhibition of mallotojaponin was foundto be competitive with respect to the template primer(rA)n (dT)12ndash18 and noncompetitive with respect to thetriphosphate substrate dTTPThe Ki value of mallotojaponinfor HIV-reverse transcriptase was determined to be 61 120583M[51]

416 Antitumor Activity Four known friedelane-type trit-erpenoids friedelin 3-hydroxy-DA-friedoolean-3-en-2-one 2120573-hydroxy-DA-friedooleanan-3-one and 3120572-hy-droxy-DA-friedooleanan-2-one and two known lupane-type triterpenoids lupeol and betulin were isolated fromthe stem bark of M philippinensis and were tested fortheir inhibitory effects on Epstein-Barr virus early antigen(EBV-EA) activation induced by 12-O-tetradecanoylphorbol13-acetate (TPA) The inhibitory effect of compounds 2(IC50

= 292mol ratio32 pmolTPA) and 4 (IC50

= 288) wasstronger than those of the other compounds tested and thepositive control curcumin (IC

50= 343) Compound 3120572-

hydroxy-DA-friedooleanan-2-one strongly inhibited mouse

10 BioMed Research International

skin tumor promotion in an in vivo two-stage carcinogenesismodel [46]

417 Wound Healing and Mesenchymal Stem Cell (MSC)Proliferation Bark extract ofMallotus philippinensis has beentested in vitro for wound healing activity by examining theproliferation and migration of MSCs KUM6 cells prolifer-ation and migration have been enhanced at 016ndash4 120583gmLand unregulated the activity of MSCs by secreting variouscytokines to wounded site from bone marrow to systemiccirculation and finally remodel wounded tissues [52]

418 Toxicities Seeds of M philippinensis ethereal extracthave adverse effect on various parameters of female rats Eventhe extract reduces serum levels of gonadotropins in treatedanimals at high dose of 100mgkg body weight Reducedweights of ovary and uterus follicular development andincreased atretic follicular in the ovary are due to subnormallevels of steroid hormones Thus pregnancy is very difficultin female rats treated with kamala seed extract [22]

419 Colouring Agent-Dye Glandular hairs of fruit aremostly used as an orange dye for silk [53 54]

5 Pharmacognostic Evaluation ofMallotus philippinensis

Morphological study shows that fruit depresses globoseand is three-lobed capsule 5ndash7mm times 8ndash10ndash12mm stellate-puberulose and with abundant orange or reddish glan-dular granules Seeds are subglobose and black in colorOrganoleptic property of the red fruit shows that it is tastelessand odourless Microscopic description showed the presenceof epicarp which contained a compactly packed layer ofmucilaginous cells and mesocarp composed of columnarcells which are closely arranged Its polygonal cells are com-pactly arranged in 2-3 layers Presence of lignified vasculararrangement has been observed in the transverse section [55]

6 Conclusion and Future Perspective

Medicinal plants have been clinically used and its interest hasbeen dramatically increased over the past decades throughoutthe world and its formulations are increasingly cited inmedia Daily consumption of the natural products and theirformulations by an extensive number of patients lead toserious concern for scientist to study its efficacy and safetyBecause of extensive use and its benefits natural productsin many countries are regulated both as medicinal productsand as food supplements often labeled as natural foodsupplements

Traditional use and its growing demand for Mallotusphilippinensis and its other species lead to compile this reviewand commented on the current knowledge provided byclinical and preclinical research on the effect of this plant

Mallotus philippinensis has been widely used as tradi-tional medicine in several parts of countries including IndiaEvery part of this plant possesses its specific medicinal prop-erties and is usedmainly in ayurveda to fight against intestinalworms in domestic and grazing animals when administeredwith jaggeryHowever only a few reports are attributed to thisplant and its different parts and there is a large scope for inves-tigation Hence it is required to explore more of its potentialwithin the field of medicinal and pharmaceutical sciences fornovel and fruitful application of this plant in form of naturalformulation Along with this medicinal importance thisplant is used against human pathogens including H pylorianti-inflammatory activity antioxidant antiradical proteininhibition hepatoprotective antiallergic anti-HIV activityand many more Phytochemical investigation revealed that alarge number phenol derivatives and several miscellaneouscompounds from different classes have been isolated fromthis species The phenols diterpenoids steroids flavonoidscardenolides triterpenoids coumarins and isocoumarinsare mostly distributed in all parts of the plant The othermajor isolated pure compounds from this species mostlybelong to phenolic group exhibiting most of the biologicalactivity Various types of extracts from different parts andsingle compounds derived from this species have beenfound to possess biological activities including antioxidantantimicrobial anti-inflammatory cytotoxicity and immunemodulatory Fruit and bark of plant contain condensed tan-nins responsible for antioxidant activity Somenovel chalconederivatives mallotophilippens C D and E were isolatedfrom the fruits of M philippinensis Mallotoxin or rottlerinhas great anticancerous potential Among the ever-anticanceragents rottlerin appears to have great potentiality for beingused in chemotherapy Rottlerin will become a potentialmolecule for research in future to treat cancerous cell as itwill affect cell machineries involved in apoptosis survivaland autophage This suggests the view that this species haspotential to be a beneficial chemotherapeutic remedy

Although the data and other reports provided that thismedicinal plant is of great biological use in different phar-macological activities including anticancer further researchis needed in different areas regarding the toxicity and efficacyof pure phytochemicals isolated from different parts of thisplant More data will be needed from preclinical and clinicalstudies on humans to clarify its potency and safety aslack of knowledge with respect to its adverse effects andmethodological accuracy in the literature limits towardsits standardized formulation Furthermore the mechanismof action of the phytochemicals and extract of Mallotusphilippinensis is unclear more exhaustive studies will beperformed to explore its mechanism and structure activityrelationship among various constituents

In conclusion this review confirms the great potential ofMallotus philippinensis As very limited information is stillknown for this species it leads us to continue the study ondifferent species of Mallotus plant and its interesting phar-macological properties Further natural product chemistryof isolated moiety and its structural analysis of compounds

BioMed Research International 11

responsible for these activities will be an interesting field ofresearch

Conflict of Interests

The authors declare that there is no conflict of interests re-garding the publication of this paper

Acknowledgment

The authors gratefully acknowledge the financial supportprovided by CSIR Government of India New Delhi forawarding SRF in the form of research fellowship

References

[1] C-J Widen and H S Puri ldquoNatural occurrence and chemicalvariability of phloroglucinols inKamalardquoPlantaMedica vol 40no 3 pp 284ndash287 1980

[2] R Singh K C Singhal and N U Khan ldquoAntifilarial activity ofMallotus philippinensisLam on Setaria cervie (Nematoda Filar-ioidea) in-vitrordquo Indian Journal of Physiology andPharmacologyvol 41 no 4 pp 397ndash403 1997

[3] V P Kumar N S Chauhan H Padh and M Rajani ldquoSearchfor antibacterial and antifungal agents from selected Indianmedicinal plantsrdquo Journal of Ethnopharmacology vol 107 no2 pp 182ndash188 2006

[4] S Shrikumar and T K Ravi ldquoApproaches towards developmentand promotion of herbal drugsrdquo Pharmaceutical Reviews vol 1no 1 pp 180ndash183 2007

[5] C Orwa A Mutua and R Kindt ldquoAgroforestree Database atree reference and selection guiderdquo Version 4 0 2009

[6] K Usmanghani A Saeed and M T Alam ldquoIndusynicMedicine Karachirdquo Research Institute of Indusyunic Medicinevol 1997 pp 285ndash287 1997

[7] F Ahmad and S Hashmi ldquoAdulteration in commercial Kamila(Mallotus philippinensisMuell) an anthelmintic drug of reputerdquoHamdard Medicus vol 38 pp 62ndash67 1995

[8] K D Roberts E Weiss and T Reichstein ldquoGlycosides andaglycons CCLII Cardenolides of the seed of Mallotus philip-pinensisrdquo Helvetica Chimica Acta vol 46 pp 2886ndash2893 1963

[9] M Bandopadhyay V K Dhingra and S K Mukerjee ldquoTriter-penoid and other components of Mallotus philippinensisrdquo Phy-tochemistry vol 11 no 4 p 1511 1972

[10] S P Nair and J Madhusudana Rao ldquoKamaladiol-3-acetate fromthe stem bark of Mallotus philippinensisrdquo Phytochemistry vol32 pp 407ndash409 1993

[11] J DWansi JWandjiW A Kamdem et al ldquoTriterpenoids fromDrypetes chevalieri Beille (Euphorbiaceae)rdquo Natural ProductResearch vol 20 no 6 pp 586ndash592 2006

[12] P Castenada A Bahena and E Garcia ldquoChemical studieson Mexican plants used in traditional medicine XXIX Sec-ondary metabolites from the stem bark of Celaeno-dendronmexicanumrdquo Journal of Natural Products vol 56 pp 1575ndash15791993

[13] T Tanaka T Ito M Iinuma Y Takahashi and H NaganawaldquoDimeric chalcone derivatives from Mallotus philippinensisrdquoPhytochemistry vol 48 no 8 pp 1423ndash1427 1998

[14] T M Nguyen V M Chau V K Phan et al ldquoStudy on chemicalconstituents of the leaves of Mallotus philippinensisrdquo Tap ChiHoa Hoc vol 48 pp 352ndash357 2010

[15] M Furusawa Y Ido T Tanaka et al ldquoNovel complex flavonoidsfrom Mallotus philippinensis (Kamala tree)rdquo Helvetica ChimicaActa vol 88 no 5 pp 1048ndash1058 2005

[16] M Lounasmaa C J Widen C M Tuuf and A HuhtikangasldquoOn the phloroglucinol derivatives of Mallotus philippinensisrdquoPlanta Medica vol 28 no 1 pp 16ndash31 1975

[17] S F H Zaidi I Yoshida F Butt et al ldquoPotent bactericidal con-stituents from Mallotus philippinensis against clarithromycinand metronidazole resistant strains of Japanese and Pakistanihelicobacter pylorirdquo Biological and Pharmaceutical Bulletin vol32 no 4 pp 631ndash636 2009

[18] M Arfan H Amin M Karamac et al ldquoAntioxidant activityof extracts of Mallotus philippinensis fruit and barkrdquo Journal ofFood Lipids vol 14 no 3 pp 280ndash297 2007

[19] M Arfan K Hazrat and K Magdalena ldquoAntioxidant activityof phenolic fractions of Mallotus philippinensis bark extractrdquoJournal of Food Science vol 27 no 2 pp 109ndash117 2009

[20] R Saijo G Nonaka and I Nishioka ldquoTannins and related com-pounds LXXXVIII Isolation and characterization of hydrolyz-able tannins fromMallotus japonicus (Thunb)Mueller-Arg andM philippinensis (Lam)Mueller-ArgrdquoChemical amp Pharmaceu-tical Bulletin vol 37 no 11 pp 2940ndash2947 1989

[21] S C Gupta S S Gupta and J S Aggarwal ldquoChemical exami-nation of the seeds of Mallotus philippinensis III Constitutionof kamlolenic acid isolated from the oilrdquo Journal of Scientific ampIndustrial Research vol 12 pp 240ndash242 1953

[22] S C Thakur S S Thakur S K Chaube and S P Singh ldquoAnetheral extract of Kamala (Mallotus philippinensis (Moll Arg)Lam) seed induce adverse effects on reproductive parametersof female ratsrdquo Reproductive Toxicology vol 20 no 1 pp 149ndash156 2005

[23] M L Gujral D R Varma K N Sareen and A K Roy ldquoOralcontraceptives II Antifertility effect ofMallotus philippinensisrdquoIndian Journal of Medical Research vol 48 pp 52ndash58 1960

[24] KMoorthy K Srinivasan C Subramanian CMohanasundariand M Palaniswamy ldquoPhyto-chemical screening and antibac-terial evaluation of stem bark of Mallotus philippinensis varTomentosusrdquoAfrican Journal of Biotechnology vol 6 no 13 pp1521ndash1523 2007

[25] M Gangwar D Kumar R Tilak et al ldquoQualitative phy-tochemical characterization and antibacterial evaluation ofglandular hairs ofMallotus philippinensis fruit extractrdquo Journalof Pharmacy Research vol 4 no 11 pp 4214ndash4216 2011

[26] A Daikonya S Katsuki and S Kitanaka ldquoAntiallergic agentsfrom naturalsources 9 Inhibition of nitric oxide productionby novel chalcone derivatives from Mallotus philippinensis(Euphorbiaceae)rdquo Chemical amp Pharmaceutical Bulletin vol 52no 11 pp 1326ndash1329 2004

[27] M Gschwendt H J Muller K Kielbassa et al ldquoRottlerina novel protein kinase inhibitorrdquo Biochemical and BiophysicalResearch Communications vol 199 no 1 pp 93ndash98 1994

[28] Y F Liao Y C Hung W H Chang et al ldquoThe PKC deltainhibitor rottlerin induces apoptosis of haematopoietic celllines through mitochondrial membrane depolarization andcaspasescascaderdquo Life Sciences vol 77 no 6 pp 707ndash719 2005

[29] H S Kang E K Park K H Kim et al ldquoReceptor activatorof nuclear factor-kappa B is induced by a rottlerin-sensitiveand p38 MAP kinase-dependent pathway during monocytedifferentiationrdquoMolecules and Cells vol 17 no 3 pp 438ndash4452004

12 BioMed Research International

[30] S P Soltoff ldquoRottlerin an inappropriate and ineffectiveinhibitor of PKC120575rdquo Trends in Pharmacological Sciences vol 28no 9 pp 453ndash458 2007

[31] Y Choi D K Kim S S Kang J K Sonn and E J Jin ldquoIntegrinsignaling and cell spreading alterations by rottlerin treatment ofchick limb bud mesenchymal cellsrdquo Biochimie vol 91 no 5 pp624ndash631 2009

[32] C Springael S Thomas S Rahmouni et al ldquoRottlerin inhibitshuman T cell responsesrdquo Biochemical Pharmacology vol 73 no4 pp 515ndash525 2007

[33] J H Choi Y P Hwang E H Han et al ldquoInhibition of acrolein-stimulated MUC5AC expression by Platycodon grandiflorumroot-derived saponin in A549 cellsrdquo Food and Chemical Toxi-cology vol 49 no 9 pp 2157ndash2166 2011

[34] E L M Guimaraes C Empsen A Geerts and L A vanGrunsven ldquoAdvanced glycation end products induce produc-tion of reactive oxygen species via the activation of NADPHoxidase in murine hepatic stellate cellsrdquo Journal of Hepatologyvol 52 no 3 pp 389ndash397 2010

[35] H Mizuguchi T Terao M Kitai et al ldquoInvolvement of pro-tein kinase C120575extracellular signal-regulated kinasepoly(ADP-ribose) polymerase-1 (PARP-1) signaling pathway in histamine-induced up-regulation of histamine H1 receptor gene expres-sion in HeLa cellsrdquo Journal of Biological Chemistry vol 286 no35 pp 30542ndash30551 2011

[36] S Ramakrishna K M Geetha P V V S Bhaskar gopalR P Kumar C P Madav and L Umachandar ldquoEffect ofMallotus PhilippinensisMuell-Arg leaves against hepatotoxicityof Carbon tetrachloride in ratsrdquo International Journal of Phar-maceutical Sciences and Research vol 2 pp 74ndash83 2011

[37] V Sharma ldquoA polyphenolic compound rottlerin demonstratessignificant in vitro cytotoxicity against human cancer celllines isolation and characterization from the fruits ofMallotusphilippinensisrdquo Journal of Plant Biochemistry and Biotechnologyvol 20 no 2 pp 190ndash195 2011

[38] M S Akhtar and I Ahmad ldquoComparative efficacy of Mallotusphilippinensis fruit (Kamala) or Nilzan drug against gastroin-testinal cestodes in Beetal goatsrdquo Small Ruminant Research vol8 no 1-2 pp 121ndash128 1992

[39] A Jabbar M A Raza Z Iqbal and M N Khan ldquoAn inventoryof the ethnobotanicals used as anthelmintics in the southernPunjab (Pakistan)rdquo Journal of Ethnopharmacology vol 108 no1 pp 152ndash154 2006

[40] M Gangwar A Dalai A Chaudhary et al ldquoStudy on activityof alcoholic extract of glands and hairs of fruits of Mallotusphilippinensis in murine cestodal infection modelrdquo Interna-tional Journal of Pharmacy amp Pharmaceutical Sciences vol 4no 1 pp 643ndash645 2012

[41] M Gangwar V C Verma T D Singh S K Singh R KGoel and G Nath ldquoIn-vitro scolicidal activity of Mallotusphilippinensis (Lam) Muell Arg fruit glandular hair extractagainst hydatid cyst Echinococcus granulosusrdquo Asian PacificJournal of Tropical Medicine vol 6 no 8 pp 595ndash601 2013

[42] S S Gupta P Verma and K Hishikar ldquoPurgative andanthelmintic effects of Mallotus philippinensis in rats againsttape wormrdquo Indian Journal of Physiology amp Pharmacology vol28 no 1 pp 63ndash66 1984

[43] A Hussain M N Khan Z Iqbal and M S Sajid ldquoAn accountof the botanical anthelmintics used in traditional veterinarypractices in Sahiwal district of Punjab Pakistanrdquo Journal ofEthnopharmacology vol 119 no 1 pp 185ndash190 2008

[44] Q Hong D E Minter S G Franzblau M Arfan H Amin andM G Reinecke ldquoAnti-tuberculosis compounds from Mallotusphilippinensisrdquo Natural Product Communications vol 5 no 2pp 211ndash217 2010

[45] V K Gupta C Shukla G R S Bisht D Saikia S Kumarand R L Thakur ldquoDetection of anti-tuberculosis activity insome folklore plants by radiometric BACTEC assayrdquo Letters inApplied Microbiology vol 52 no 1 pp 33ndash40 2011

[46] R Tanaka T Nakata C Yamaguchi S Wada T Yamadaand H Tokuda ldquoPotential anti-tumor-promoting activity of3120572-Hydroxy-D a-friedooleanan-2-one from the stem bark ofMallotus philippinensisrdquo Planta Medica vol 74 no 4 pp 413ndash416 2008

[47] A Daikonya S Katsuki J B Wu and S Kitanaka ldquoAnti-allergic agents from natural sources (4) anti-allergic activityof new phloroglucinol derivatives from Mallotus philippinensis(Euphorbiaceae)rdquo Chemical and Pharmaceutical Bulletin vol50 no 12 pp 1566ndash1569 2002

[48] T K Chan S W David C Cheng S P Guan H MKoh and W S Wong ldquoAnti-allergic actions of rottlerin fromMallotus philippinensisis in experimental mast cell-mediatedanaphylactic modelsrdquo Phytomedicine vol 20 no 10 pp 853ndash860 2013

[49] M Khan R A Qureshi M Hussain K Mehmood and R AKhan ldquoHexane soluble extract ofMallotus philippinensis (Lam)Muell Arg root possesses anti-leukaemic activityrdquo ChemistryCentral Journal vol 7 no 1 article 157 2013

[50] R Roshan S G Kulkarni S P Tupe et al ldquoAntifungal dimericchalcone derivative kamalachalcone E from Mallotus philip-pinensisrdquo Natural Product Research Formerly Natural ProductLetters vol 28 no 4 pp 245ndash250 2014

[51] H Nakane M Arisawa A Fujita S Koshimura and KOno ldquoInhibition of HIV-reverse transcriptase activity by somephloroglucinol derivativesrdquo FEBS Letters vol 286 no 1-2 pp83ndash85 1991

[52] T Furumoto N Ozawa Y Inami et al ldquoMallotus philippinensisbark extracts promote preferential migration of mesenchymalstem cells and improve wound healing in micerdquo Phytomedicinevol 21 no 3 pp 247ndash253 2014

[53] Maeda ldquoMethod for producing Mallotus philippinensis dyecomposition and the compositionrdquo US7556829 B2 2009

[54] C Wiart Medicinal Plants of the Asia-Pacific Drugs for theFutureWorld Scientific Singapore 2006

[55] V R Sharma ldquoA review on endangered plant of Mallotusphilippinensis (Lam) MArgrdquo Pharmacologyonline vol 3 pp1256ndash1265 2011

[56] V Tangpu T Temjenmongla and A K Yadav ldquoAnticestodalproperty of Strobilanthes discolor an experimental study inHymenolepis diminutamdashratmodelrdquo Journal of Ethnopharmacol-ogy vol 105 no 3 pp 459ndash463 2006

[57] V Tangpu K Temjenmongla and A K Yadav ldquoAnticestodalactivity ofTrifolium repens extractrdquo Pharmaceutical Biology vol42 no 8 pp 656ndash658 2004

[58] A K Yadav and T Temjenmongla ldquoAnticestodal activity ofHouttuynia cordata leaf extract againstHymenolepis diminuta inexperimentally infected ratsrdquo Journal of Parasitic Diseases vol35 no 2 pp 190ndash194 2011

[59] T Temjenmongla and A K Yadav ldquoAnticestodal efficacy ofLasia spinosa extract against experimental Hymenolepis dimin-uta infections in ratsrdquo Pharmaceutical Biology vol 44 no 7 pp499ndash502 2006

BioMed Research International 13

[60] M L Dhar M M Dhar B N Dhawan B N Mehrotra and CRay ldquoScreening of Indian plants for biological activityrdquo IndianJournal of Experimental Biology vol 6 no 4 pp 232ndash247 1968

[61] Temjenmongla and A K Yadav ldquoAnticestodal efficacy offolklore medicinal plants of Naga tribes in north-east IndiardquoAfrican Journal of Traditional Complementary and AlternativeMedicines vol 2 pp 129ndash133 2005

[62] T V Tangpu and A K Yadav ldquoAnticestodal efficacy of Psidiumguajava against experimental Hymenolepis diminuta infectionin ratsrdquo Indian Journal of Pharmacology vol 38 no 1 pp 29ndash32 2006

[63] R Singh A Mehta P Mehta and K Shukla ldquoAnthelminticactivity of Rhizome extracts of Curcuma longa and Zingiberofficinalerdquo International Journal of Pharmacy and Pharmaceu-tical Sciences vol 3 no 2 pp 236ndash237 2011

[64] M K Asha D Prashanth B Murali R Padmaja and A AmitldquoAnthelmintic activity of essential oil of Ocimum sanctum andeugenolrdquo Fitoterapia vol 72 no 6 pp 669ndash670 2001

[65] J B Githiori J Hoglund P J Waller and R L Baker ldquoTheanthelmintic efficacy of the plantAlbizia anthelmintica againstthe nematode parasites Haemonchus contortus of sheep andHeligmosomoides polygyrus of micerdquo Veterinary Parasitologyvol 116 no 1 pp 23ndash34 2003

[66] N M Enwerema J I Okoguna C O Wambebea D A Oko-rieb and P A Akahc ldquoAnthelmintic activity of the stem barkextracts of Berlina grandiflora and one of its active principlesBetulinic acidrdquo Phytomedicine vol 8 pp 112ndash114 2001

[67] Z Iqbal M Lateef A Jabber M N Ghayur and A HGilani ldquoIn vitro and in vivo anthelmintic activity of Nicotianatabacum L leaves against gastrointestinal nematodes of sheeprdquoPhytotherapy Research vol 20 no 1 pp 46ndash48 2006

[68] Z Iqbal M Lateef A Jabbar G Muhammad and M N KhanldquoAnthelmintic activity of Calotropis procera (Ait) Ait F flowersin sheeprdquo Journal of Ethnopharmacology vol 102 no 2 pp 256ndash261 2005

Submit your manuscripts athttpwwwhindawicom

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Hindawi Publishing Corporationhttpwwwhindawicom

Volume 2014

ToxinsJournal of

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Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

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Medicinal ChemistryInternational Journal of

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Autoimmune Diseases

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MEDIATORSINFLAMMATION

of

Page 9: Mallotus philippinensis Muell. Arg (Euphorbiaceae ...

BioMed Research International 9

assessed from resins isolated from plant Its effect was evalu-ated from the weight of faeces as well as from surface areaof blotting paper soaked by liquid faeces The anthelminticeffect on tape worm was evaluated in albino rates fromthe resin of the plant showed lethal effect of 3569 and7821 respectively in small intestine in concentrations 60and 120mgkg respectively [42 43]

411 Antituberculosis Activity Organic extract of plant afterbioassay-directed fractionation yields five compounds themost active of which againstMycobacterium tuberculosis wasa new compound 8-cinnamoyl-57-dihydroxy-22-dimethyl-6-geranylchromene for which the name mallotophilippenF is suggested The second compound 8-cinnamoyl-22-dimethyl-7-hydroxy-5-methoxychromene was isolated froma natural source for the first time while the remaining threecompounds rottlerin isoallorottlerin or isorottlerin andthe so-called ldquored compoundrdquo 8-cinnamoyl-57-dihydroxy-226-trimethylchromene had been already isolated fromthis plant Isolated compounds were identified by 2D-NMRand C-13 NMR [44] Ethanolic extract of plant was assayedfor antimycobacterial activity against M smegmatis by discdiffusion assay Further antituberculosis potential of leavesextract was identified by radiometric BACTEC assay resultrevealed that ethanolic extract ofM philippensis showed anti-tuberculosis activity against virulent and avirulent strains ofM tuberculosis H37Rv andM tuberculosis H37Ra with min-imum inhibitory concentrations of 025 and 0125mgmLminus1respectively The inhibition in growth index values of Mtuberculosis was observed in the presence of ethyl acetatefraction at a minimum concentration of 005mgmLminus1 Itsuggests that ethanolic and ethyl acetate fraction of plantpossesses significant antimycobacterial activity [45] Steambark of M philippinensis has also been reported for itsantitumor promoting effect which was due to the presenceof 3120572-Hydroxy-DA-friedooleanan-2-one [46]

412 Antiallergic Activity M philippinensis fruit containstwo new phloroglucinol derivatives mallotophilippensA and B (Figures 10 and 11) which were identified usingchemical and spectral data as 1-[57-dihydroxy-22-di-methyl-6-(246-trihydroxy-3-isobutyryl-5-methyl-benzyl)-2H-chromen-8-yl]-2-methyl-butan-1-one and 1-[6-(3-Acetyl-246-trihydroxy-5-methyl-benzyl)-57-dihydroxy-22-dim-ethyl-2H-chromen-8-yl]-2-methyl-butan-1-one respe-ctively These compounds inhibited the production ofnitric oxide (NO) and inducible NO synthase (iNOS) geneexpression by a murine macrophage-like cell line (RAW2647) which was activated by lipopolysaccharide (LPS)and recombinant mouse interferon-g (IFN-g) Furtherphloroglucinol derivatives inhibit histamine release from ratperitoneal mast cells induced by compound 4880This studysuggests its anti-inflammatory activity [47] Rottlerin hasbeen tested in animal models of IgE-dependent anaphylaxisand the antiallergic mechanisms of action in mast cellsAntiallergic action of rottlerin has been tested in passivecutaneous anaphylaxis and passive systemic anaphylaxismouse models and in anaphylactic contraction of bronchial

rings isolated from sensitized guinea pigs This experimentsproves antiallergic effect of rottlerin by blocking IgE-inducedmast cell degranulation This report suggests the use ofrottlerin in mast cell-mediated allergic disorders includingurticaria and allergic asthma [48]

413 Anti-Leukaemic Activity Root extract ofM philippinen-sis was tested on human promyelocytic leukemia HL-60 cellproliferation cell cycle regulators and apoptosis in order toinvestigate its antileukemic effect Hexane fraction showedpromising toxicity against p53-deficient HL-60 cells (IC

50

15mg dry roots equivalentmL medium) after 72 h andinterestingly inhibition of cell proliferation was preceded bythe upregulation of the protooncogenes Cdc25A and cyclinD1 within 24 hours suggesting its antileukemic effect inHL-60 cells After isolation and identification by GC-MSpolyphenols were the main compounds of the hexane extractthat inhibited proliferation and induced apoptosis [49]

414 Antiproliferative Activity Antiproliferative effect wasevaluated against Thp-1 cell lines from the isolated com-pounds of M philippinensis fruit extract in which 41015840-hydroxyrottlerin showed 54 growth inhibition ofThp-1 cellline [50] Other isolated compounds were also tested againstdifferent fungi andwere found to be very effective IC

50values

415 Anti-HIV Activity Four phloroglucinol derivativesnamed mallotophenone (5-methylene-bis-26-dihydroxy-3-methyl-4-methoxyacetophenone) mallotochromene (8-acetyl-57-dihydroxy-6-(3-acetyl-24-dihydroxy-5-methyl-6-methoxybenzyl)-22-dimethylchromene) mallotojaponin(3-(33(dimethylallyl) S-(3(acetyl-24-dihydroxy-5-methyl-6-methoxybenzyl)-phloracetophenone) andmallotolerin (3-(3-methyl-2-hydroxybut-3-enyl)-5-(3-acetyl-24-dihydroxy-5-methyl-6-methoxybenzyl)-phloracetophenone) weretested for their ability to inhibit the activity of humanimmunodeficiency virus- (HIV-) reverse transcriptaseThe mode of inhibition of mallotojaponin was foundto be competitive with respect to the template primer(rA)n (dT)12ndash18 and noncompetitive with respect to thetriphosphate substrate dTTPThe Ki value of mallotojaponinfor HIV-reverse transcriptase was determined to be 61 120583M[51]

416 Antitumor Activity Four known friedelane-type trit-erpenoids friedelin 3-hydroxy-DA-friedoolean-3-en-2-one 2120573-hydroxy-DA-friedooleanan-3-one and 3120572-hy-droxy-DA-friedooleanan-2-one and two known lupane-type triterpenoids lupeol and betulin were isolated fromthe stem bark of M philippinensis and were tested fortheir inhibitory effects on Epstein-Barr virus early antigen(EBV-EA) activation induced by 12-O-tetradecanoylphorbol13-acetate (TPA) The inhibitory effect of compounds 2(IC50

= 292mol ratio32 pmolTPA) and 4 (IC50

= 288) wasstronger than those of the other compounds tested and thepositive control curcumin (IC

50= 343) Compound 3120572-

hydroxy-DA-friedooleanan-2-one strongly inhibited mouse

10 BioMed Research International

skin tumor promotion in an in vivo two-stage carcinogenesismodel [46]

417 Wound Healing and Mesenchymal Stem Cell (MSC)Proliferation Bark extract ofMallotus philippinensis has beentested in vitro for wound healing activity by examining theproliferation and migration of MSCs KUM6 cells prolifer-ation and migration have been enhanced at 016ndash4 120583gmLand unregulated the activity of MSCs by secreting variouscytokines to wounded site from bone marrow to systemiccirculation and finally remodel wounded tissues [52]

418 Toxicities Seeds of M philippinensis ethereal extracthave adverse effect on various parameters of female rats Eventhe extract reduces serum levels of gonadotropins in treatedanimals at high dose of 100mgkg body weight Reducedweights of ovary and uterus follicular development andincreased atretic follicular in the ovary are due to subnormallevels of steroid hormones Thus pregnancy is very difficultin female rats treated with kamala seed extract [22]

419 Colouring Agent-Dye Glandular hairs of fruit aremostly used as an orange dye for silk [53 54]

5 Pharmacognostic Evaluation ofMallotus philippinensis

Morphological study shows that fruit depresses globoseand is three-lobed capsule 5ndash7mm times 8ndash10ndash12mm stellate-puberulose and with abundant orange or reddish glan-dular granules Seeds are subglobose and black in colorOrganoleptic property of the red fruit shows that it is tastelessand odourless Microscopic description showed the presenceof epicarp which contained a compactly packed layer ofmucilaginous cells and mesocarp composed of columnarcells which are closely arranged Its polygonal cells are com-pactly arranged in 2-3 layers Presence of lignified vasculararrangement has been observed in the transverse section [55]

6 Conclusion and Future Perspective

Medicinal plants have been clinically used and its interest hasbeen dramatically increased over the past decades throughoutthe world and its formulations are increasingly cited inmedia Daily consumption of the natural products and theirformulations by an extensive number of patients lead toserious concern for scientist to study its efficacy and safetyBecause of extensive use and its benefits natural productsin many countries are regulated both as medicinal productsand as food supplements often labeled as natural foodsupplements

Traditional use and its growing demand for Mallotusphilippinensis and its other species lead to compile this reviewand commented on the current knowledge provided byclinical and preclinical research on the effect of this plant

Mallotus philippinensis has been widely used as tradi-tional medicine in several parts of countries including IndiaEvery part of this plant possesses its specific medicinal prop-erties and is usedmainly in ayurveda to fight against intestinalworms in domestic and grazing animals when administeredwith jaggeryHowever only a few reports are attributed to thisplant and its different parts and there is a large scope for inves-tigation Hence it is required to explore more of its potentialwithin the field of medicinal and pharmaceutical sciences fornovel and fruitful application of this plant in form of naturalformulation Along with this medicinal importance thisplant is used against human pathogens including H pylorianti-inflammatory activity antioxidant antiradical proteininhibition hepatoprotective antiallergic anti-HIV activityand many more Phytochemical investigation revealed that alarge number phenol derivatives and several miscellaneouscompounds from different classes have been isolated fromthis species The phenols diterpenoids steroids flavonoidscardenolides triterpenoids coumarins and isocoumarinsare mostly distributed in all parts of the plant The othermajor isolated pure compounds from this species mostlybelong to phenolic group exhibiting most of the biologicalactivity Various types of extracts from different parts andsingle compounds derived from this species have beenfound to possess biological activities including antioxidantantimicrobial anti-inflammatory cytotoxicity and immunemodulatory Fruit and bark of plant contain condensed tan-nins responsible for antioxidant activity Somenovel chalconederivatives mallotophilippens C D and E were isolatedfrom the fruits of M philippinensis Mallotoxin or rottlerinhas great anticancerous potential Among the ever-anticanceragents rottlerin appears to have great potentiality for beingused in chemotherapy Rottlerin will become a potentialmolecule for research in future to treat cancerous cell as itwill affect cell machineries involved in apoptosis survivaland autophage This suggests the view that this species haspotential to be a beneficial chemotherapeutic remedy

Although the data and other reports provided that thismedicinal plant is of great biological use in different phar-macological activities including anticancer further researchis needed in different areas regarding the toxicity and efficacyof pure phytochemicals isolated from different parts of thisplant More data will be needed from preclinical and clinicalstudies on humans to clarify its potency and safety aslack of knowledge with respect to its adverse effects andmethodological accuracy in the literature limits towardsits standardized formulation Furthermore the mechanismof action of the phytochemicals and extract of Mallotusphilippinensis is unclear more exhaustive studies will beperformed to explore its mechanism and structure activityrelationship among various constituents

In conclusion this review confirms the great potential ofMallotus philippinensis As very limited information is stillknown for this species it leads us to continue the study ondifferent species of Mallotus plant and its interesting phar-macological properties Further natural product chemistryof isolated moiety and its structural analysis of compounds

BioMed Research International 11

responsible for these activities will be an interesting field ofresearch

Conflict of Interests

The authors declare that there is no conflict of interests re-garding the publication of this paper

Acknowledgment

The authors gratefully acknowledge the financial supportprovided by CSIR Government of India New Delhi forawarding SRF in the form of research fellowship

References

[1] C-J Widen and H S Puri ldquoNatural occurrence and chemicalvariability of phloroglucinols inKamalardquoPlantaMedica vol 40no 3 pp 284ndash287 1980

[2] R Singh K C Singhal and N U Khan ldquoAntifilarial activity ofMallotus philippinensisLam on Setaria cervie (Nematoda Filar-ioidea) in-vitrordquo Indian Journal of Physiology andPharmacologyvol 41 no 4 pp 397ndash403 1997

[3] V P Kumar N S Chauhan H Padh and M Rajani ldquoSearchfor antibacterial and antifungal agents from selected Indianmedicinal plantsrdquo Journal of Ethnopharmacology vol 107 no2 pp 182ndash188 2006

[4] S Shrikumar and T K Ravi ldquoApproaches towards developmentand promotion of herbal drugsrdquo Pharmaceutical Reviews vol 1no 1 pp 180ndash183 2007

[5] C Orwa A Mutua and R Kindt ldquoAgroforestree Database atree reference and selection guiderdquo Version 4 0 2009

[6] K Usmanghani A Saeed and M T Alam ldquoIndusynicMedicine Karachirdquo Research Institute of Indusyunic Medicinevol 1997 pp 285ndash287 1997

[7] F Ahmad and S Hashmi ldquoAdulteration in commercial Kamila(Mallotus philippinensisMuell) an anthelmintic drug of reputerdquoHamdard Medicus vol 38 pp 62ndash67 1995

[8] K D Roberts E Weiss and T Reichstein ldquoGlycosides andaglycons CCLII Cardenolides of the seed of Mallotus philip-pinensisrdquo Helvetica Chimica Acta vol 46 pp 2886ndash2893 1963

[9] M Bandopadhyay V K Dhingra and S K Mukerjee ldquoTriter-penoid and other components of Mallotus philippinensisrdquo Phy-tochemistry vol 11 no 4 p 1511 1972

[10] S P Nair and J Madhusudana Rao ldquoKamaladiol-3-acetate fromthe stem bark of Mallotus philippinensisrdquo Phytochemistry vol32 pp 407ndash409 1993

[11] J DWansi JWandjiW A Kamdem et al ldquoTriterpenoids fromDrypetes chevalieri Beille (Euphorbiaceae)rdquo Natural ProductResearch vol 20 no 6 pp 586ndash592 2006

[12] P Castenada A Bahena and E Garcia ldquoChemical studieson Mexican plants used in traditional medicine XXIX Sec-ondary metabolites from the stem bark of Celaeno-dendronmexicanumrdquo Journal of Natural Products vol 56 pp 1575ndash15791993

[13] T Tanaka T Ito M Iinuma Y Takahashi and H NaganawaldquoDimeric chalcone derivatives from Mallotus philippinensisrdquoPhytochemistry vol 48 no 8 pp 1423ndash1427 1998

[14] T M Nguyen V M Chau V K Phan et al ldquoStudy on chemicalconstituents of the leaves of Mallotus philippinensisrdquo Tap ChiHoa Hoc vol 48 pp 352ndash357 2010

[15] M Furusawa Y Ido T Tanaka et al ldquoNovel complex flavonoidsfrom Mallotus philippinensis (Kamala tree)rdquo Helvetica ChimicaActa vol 88 no 5 pp 1048ndash1058 2005

[16] M Lounasmaa C J Widen C M Tuuf and A HuhtikangasldquoOn the phloroglucinol derivatives of Mallotus philippinensisrdquoPlanta Medica vol 28 no 1 pp 16ndash31 1975

[17] S F H Zaidi I Yoshida F Butt et al ldquoPotent bactericidal con-stituents from Mallotus philippinensis against clarithromycinand metronidazole resistant strains of Japanese and Pakistanihelicobacter pylorirdquo Biological and Pharmaceutical Bulletin vol32 no 4 pp 631ndash636 2009

[18] M Arfan H Amin M Karamac et al ldquoAntioxidant activityof extracts of Mallotus philippinensis fruit and barkrdquo Journal ofFood Lipids vol 14 no 3 pp 280ndash297 2007

[19] M Arfan K Hazrat and K Magdalena ldquoAntioxidant activityof phenolic fractions of Mallotus philippinensis bark extractrdquoJournal of Food Science vol 27 no 2 pp 109ndash117 2009

[20] R Saijo G Nonaka and I Nishioka ldquoTannins and related com-pounds LXXXVIII Isolation and characterization of hydrolyz-able tannins fromMallotus japonicus (Thunb)Mueller-Arg andM philippinensis (Lam)Mueller-ArgrdquoChemical amp Pharmaceu-tical Bulletin vol 37 no 11 pp 2940ndash2947 1989

[21] S C Gupta S S Gupta and J S Aggarwal ldquoChemical exami-nation of the seeds of Mallotus philippinensis III Constitutionof kamlolenic acid isolated from the oilrdquo Journal of Scientific ampIndustrial Research vol 12 pp 240ndash242 1953

[22] S C Thakur S S Thakur S K Chaube and S P Singh ldquoAnetheral extract of Kamala (Mallotus philippinensis (Moll Arg)Lam) seed induce adverse effects on reproductive parametersof female ratsrdquo Reproductive Toxicology vol 20 no 1 pp 149ndash156 2005

[23] M L Gujral D R Varma K N Sareen and A K Roy ldquoOralcontraceptives II Antifertility effect ofMallotus philippinensisrdquoIndian Journal of Medical Research vol 48 pp 52ndash58 1960

[24] KMoorthy K Srinivasan C Subramanian CMohanasundariand M Palaniswamy ldquoPhyto-chemical screening and antibac-terial evaluation of stem bark of Mallotus philippinensis varTomentosusrdquoAfrican Journal of Biotechnology vol 6 no 13 pp1521ndash1523 2007

[25] M Gangwar D Kumar R Tilak et al ldquoQualitative phy-tochemical characterization and antibacterial evaluation ofglandular hairs ofMallotus philippinensis fruit extractrdquo Journalof Pharmacy Research vol 4 no 11 pp 4214ndash4216 2011

[26] A Daikonya S Katsuki and S Kitanaka ldquoAntiallergic agentsfrom naturalsources 9 Inhibition of nitric oxide productionby novel chalcone derivatives from Mallotus philippinensis(Euphorbiaceae)rdquo Chemical amp Pharmaceutical Bulletin vol 52no 11 pp 1326ndash1329 2004

[27] M Gschwendt H J Muller K Kielbassa et al ldquoRottlerina novel protein kinase inhibitorrdquo Biochemical and BiophysicalResearch Communications vol 199 no 1 pp 93ndash98 1994

[28] Y F Liao Y C Hung W H Chang et al ldquoThe PKC deltainhibitor rottlerin induces apoptosis of haematopoietic celllines through mitochondrial membrane depolarization andcaspasescascaderdquo Life Sciences vol 77 no 6 pp 707ndash719 2005

[29] H S Kang E K Park K H Kim et al ldquoReceptor activatorof nuclear factor-kappa B is induced by a rottlerin-sensitiveand p38 MAP kinase-dependent pathway during monocytedifferentiationrdquoMolecules and Cells vol 17 no 3 pp 438ndash4452004

12 BioMed Research International

[30] S P Soltoff ldquoRottlerin an inappropriate and ineffectiveinhibitor of PKC120575rdquo Trends in Pharmacological Sciences vol 28no 9 pp 453ndash458 2007

[31] Y Choi D K Kim S S Kang J K Sonn and E J Jin ldquoIntegrinsignaling and cell spreading alterations by rottlerin treatment ofchick limb bud mesenchymal cellsrdquo Biochimie vol 91 no 5 pp624ndash631 2009

[32] C Springael S Thomas S Rahmouni et al ldquoRottlerin inhibitshuman T cell responsesrdquo Biochemical Pharmacology vol 73 no4 pp 515ndash525 2007

[33] J H Choi Y P Hwang E H Han et al ldquoInhibition of acrolein-stimulated MUC5AC expression by Platycodon grandiflorumroot-derived saponin in A549 cellsrdquo Food and Chemical Toxi-cology vol 49 no 9 pp 2157ndash2166 2011

[34] E L M Guimaraes C Empsen A Geerts and L A vanGrunsven ldquoAdvanced glycation end products induce produc-tion of reactive oxygen species via the activation of NADPHoxidase in murine hepatic stellate cellsrdquo Journal of Hepatologyvol 52 no 3 pp 389ndash397 2010

[35] H Mizuguchi T Terao M Kitai et al ldquoInvolvement of pro-tein kinase C120575extracellular signal-regulated kinasepoly(ADP-ribose) polymerase-1 (PARP-1) signaling pathway in histamine-induced up-regulation of histamine H1 receptor gene expres-sion in HeLa cellsrdquo Journal of Biological Chemistry vol 286 no35 pp 30542ndash30551 2011

[36] S Ramakrishna K M Geetha P V V S Bhaskar gopalR P Kumar C P Madav and L Umachandar ldquoEffect ofMallotus PhilippinensisMuell-Arg leaves against hepatotoxicityof Carbon tetrachloride in ratsrdquo International Journal of Phar-maceutical Sciences and Research vol 2 pp 74ndash83 2011

[37] V Sharma ldquoA polyphenolic compound rottlerin demonstratessignificant in vitro cytotoxicity against human cancer celllines isolation and characterization from the fruits ofMallotusphilippinensisrdquo Journal of Plant Biochemistry and Biotechnologyvol 20 no 2 pp 190ndash195 2011

[38] M S Akhtar and I Ahmad ldquoComparative efficacy of Mallotusphilippinensis fruit (Kamala) or Nilzan drug against gastroin-testinal cestodes in Beetal goatsrdquo Small Ruminant Research vol8 no 1-2 pp 121ndash128 1992

[39] A Jabbar M A Raza Z Iqbal and M N Khan ldquoAn inventoryof the ethnobotanicals used as anthelmintics in the southernPunjab (Pakistan)rdquo Journal of Ethnopharmacology vol 108 no1 pp 152ndash154 2006

[40] M Gangwar A Dalai A Chaudhary et al ldquoStudy on activityof alcoholic extract of glands and hairs of fruits of Mallotusphilippinensis in murine cestodal infection modelrdquo Interna-tional Journal of Pharmacy amp Pharmaceutical Sciences vol 4no 1 pp 643ndash645 2012

[41] M Gangwar V C Verma T D Singh S K Singh R KGoel and G Nath ldquoIn-vitro scolicidal activity of Mallotusphilippinensis (Lam) Muell Arg fruit glandular hair extractagainst hydatid cyst Echinococcus granulosusrdquo Asian PacificJournal of Tropical Medicine vol 6 no 8 pp 595ndash601 2013

[42] S S Gupta P Verma and K Hishikar ldquoPurgative andanthelmintic effects of Mallotus philippinensis in rats againsttape wormrdquo Indian Journal of Physiology amp Pharmacology vol28 no 1 pp 63ndash66 1984

[43] A Hussain M N Khan Z Iqbal and M S Sajid ldquoAn accountof the botanical anthelmintics used in traditional veterinarypractices in Sahiwal district of Punjab Pakistanrdquo Journal ofEthnopharmacology vol 119 no 1 pp 185ndash190 2008

[44] Q Hong D E Minter S G Franzblau M Arfan H Amin andM G Reinecke ldquoAnti-tuberculosis compounds from Mallotusphilippinensisrdquo Natural Product Communications vol 5 no 2pp 211ndash217 2010

[45] V K Gupta C Shukla G R S Bisht D Saikia S Kumarand R L Thakur ldquoDetection of anti-tuberculosis activity insome folklore plants by radiometric BACTEC assayrdquo Letters inApplied Microbiology vol 52 no 1 pp 33ndash40 2011

[46] R Tanaka T Nakata C Yamaguchi S Wada T Yamadaand H Tokuda ldquoPotential anti-tumor-promoting activity of3120572-Hydroxy-D a-friedooleanan-2-one from the stem bark ofMallotus philippinensisrdquo Planta Medica vol 74 no 4 pp 413ndash416 2008

[47] A Daikonya S Katsuki J B Wu and S Kitanaka ldquoAnti-allergic agents from natural sources (4) anti-allergic activityof new phloroglucinol derivatives from Mallotus philippinensis(Euphorbiaceae)rdquo Chemical and Pharmaceutical Bulletin vol50 no 12 pp 1566ndash1569 2002

[48] T K Chan S W David C Cheng S P Guan H MKoh and W S Wong ldquoAnti-allergic actions of rottlerin fromMallotus philippinensisis in experimental mast cell-mediatedanaphylactic modelsrdquo Phytomedicine vol 20 no 10 pp 853ndash860 2013

[49] M Khan R A Qureshi M Hussain K Mehmood and R AKhan ldquoHexane soluble extract ofMallotus philippinensis (Lam)Muell Arg root possesses anti-leukaemic activityrdquo ChemistryCentral Journal vol 7 no 1 article 157 2013

[50] R Roshan S G Kulkarni S P Tupe et al ldquoAntifungal dimericchalcone derivative kamalachalcone E from Mallotus philip-pinensisrdquo Natural Product Research Formerly Natural ProductLetters vol 28 no 4 pp 245ndash250 2014

[51] H Nakane M Arisawa A Fujita S Koshimura and KOno ldquoInhibition of HIV-reverse transcriptase activity by somephloroglucinol derivativesrdquo FEBS Letters vol 286 no 1-2 pp83ndash85 1991

[52] T Furumoto N Ozawa Y Inami et al ldquoMallotus philippinensisbark extracts promote preferential migration of mesenchymalstem cells and improve wound healing in micerdquo Phytomedicinevol 21 no 3 pp 247ndash253 2014

[53] Maeda ldquoMethod for producing Mallotus philippinensis dyecomposition and the compositionrdquo US7556829 B2 2009

[54] C Wiart Medicinal Plants of the Asia-Pacific Drugs for theFutureWorld Scientific Singapore 2006

[55] V R Sharma ldquoA review on endangered plant of Mallotusphilippinensis (Lam) MArgrdquo Pharmacologyonline vol 3 pp1256ndash1265 2011

[56] V Tangpu T Temjenmongla and A K Yadav ldquoAnticestodalproperty of Strobilanthes discolor an experimental study inHymenolepis diminutamdashratmodelrdquo Journal of Ethnopharmacol-ogy vol 105 no 3 pp 459ndash463 2006

[57] V Tangpu K Temjenmongla and A K Yadav ldquoAnticestodalactivity ofTrifolium repens extractrdquo Pharmaceutical Biology vol42 no 8 pp 656ndash658 2004

[58] A K Yadav and T Temjenmongla ldquoAnticestodal activity ofHouttuynia cordata leaf extract againstHymenolepis diminuta inexperimentally infected ratsrdquo Journal of Parasitic Diseases vol35 no 2 pp 190ndash194 2011

[59] T Temjenmongla and A K Yadav ldquoAnticestodal efficacy ofLasia spinosa extract against experimental Hymenolepis dimin-uta infections in ratsrdquo Pharmaceutical Biology vol 44 no 7 pp499ndash502 2006

BioMed Research International 13

[60] M L Dhar M M Dhar B N Dhawan B N Mehrotra and CRay ldquoScreening of Indian plants for biological activityrdquo IndianJournal of Experimental Biology vol 6 no 4 pp 232ndash247 1968

[61] Temjenmongla and A K Yadav ldquoAnticestodal efficacy offolklore medicinal plants of Naga tribes in north-east IndiardquoAfrican Journal of Traditional Complementary and AlternativeMedicines vol 2 pp 129ndash133 2005

[62] T V Tangpu and A K Yadav ldquoAnticestodal efficacy of Psidiumguajava against experimental Hymenolepis diminuta infectionin ratsrdquo Indian Journal of Pharmacology vol 38 no 1 pp 29ndash32 2006

[63] R Singh A Mehta P Mehta and K Shukla ldquoAnthelminticactivity of Rhizome extracts of Curcuma longa and Zingiberofficinalerdquo International Journal of Pharmacy and Pharmaceu-tical Sciences vol 3 no 2 pp 236ndash237 2011

[64] M K Asha D Prashanth B Murali R Padmaja and A AmitldquoAnthelmintic activity of essential oil of Ocimum sanctum andeugenolrdquo Fitoterapia vol 72 no 6 pp 669ndash670 2001

[65] J B Githiori J Hoglund P J Waller and R L Baker ldquoTheanthelmintic efficacy of the plantAlbizia anthelmintica againstthe nematode parasites Haemonchus contortus of sheep andHeligmosomoides polygyrus of micerdquo Veterinary Parasitologyvol 116 no 1 pp 23ndash34 2003

[66] N M Enwerema J I Okoguna C O Wambebea D A Oko-rieb and P A Akahc ldquoAnthelmintic activity of the stem barkextracts of Berlina grandiflora and one of its active principlesBetulinic acidrdquo Phytomedicine vol 8 pp 112ndash114 2001

[67] Z Iqbal M Lateef A Jabber M N Ghayur and A HGilani ldquoIn vitro and in vivo anthelmintic activity of Nicotianatabacum L leaves against gastrointestinal nematodes of sheeprdquoPhytotherapy Research vol 20 no 1 pp 46ndash48 2006

[68] Z Iqbal M Lateef A Jabbar G Muhammad and M N KhanldquoAnthelmintic activity of Calotropis procera (Ait) Ait F flowersin sheeprdquo Journal of Ethnopharmacology vol 102 no 2 pp 256ndash261 2005

Submit your manuscripts athttpwwwhindawicom

PainResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom

Volume 2014

ToxinsJournal of

VaccinesJournal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AntibioticsInternational Journal of

ToxicologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

StrokeResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Drug DeliveryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in Pharmacological Sciences

Tropical MedicineJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AddictionJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

Emergency Medicine InternationalHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Autoimmune Diseases

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Anesthesiology Research and Practice

ScientificaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Pharmaceutics

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Page 10: Mallotus philippinensis Muell. Arg (Euphorbiaceae ...

10 BioMed Research International

skin tumor promotion in an in vivo two-stage carcinogenesismodel [46]

417 Wound Healing and Mesenchymal Stem Cell (MSC)Proliferation Bark extract ofMallotus philippinensis has beentested in vitro for wound healing activity by examining theproliferation and migration of MSCs KUM6 cells prolifer-ation and migration have been enhanced at 016ndash4 120583gmLand unregulated the activity of MSCs by secreting variouscytokines to wounded site from bone marrow to systemiccirculation and finally remodel wounded tissues [52]

418 Toxicities Seeds of M philippinensis ethereal extracthave adverse effect on various parameters of female rats Eventhe extract reduces serum levels of gonadotropins in treatedanimals at high dose of 100mgkg body weight Reducedweights of ovary and uterus follicular development andincreased atretic follicular in the ovary are due to subnormallevels of steroid hormones Thus pregnancy is very difficultin female rats treated with kamala seed extract [22]

419 Colouring Agent-Dye Glandular hairs of fruit aremostly used as an orange dye for silk [53 54]

5 Pharmacognostic Evaluation ofMallotus philippinensis

Morphological study shows that fruit depresses globoseand is three-lobed capsule 5ndash7mm times 8ndash10ndash12mm stellate-puberulose and with abundant orange or reddish glan-dular granules Seeds are subglobose and black in colorOrganoleptic property of the red fruit shows that it is tastelessand odourless Microscopic description showed the presenceof epicarp which contained a compactly packed layer ofmucilaginous cells and mesocarp composed of columnarcells which are closely arranged Its polygonal cells are com-pactly arranged in 2-3 layers Presence of lignified vasculararrangement has been observed in the transverse section [55]

6 Conclusion and Future Perspective

Medicinal plants have been clinically used and its interest hasbeen dramatically increased over the past decades throughoutthe world and its formulations are increasingly cited inmedia Daily consumption of the natural products and theirformulations by an extensive number of patients lead toserious concern for scientist to study its efficacy and safetyBecause of extensive use and its benefits natural productsin many countries are regulated both as medicinal productsand as food supplements often labeled as natural foodsupplements

Traditional use and its growing demand for Mallotusphilippinensis and its other species lead to compile this reviewand commented on the current knowledge provided byclinical and preclinical research on the effect of this plant

Mallotus philippinensis has been widely used as tradi-tional medicine in several parts of countries including IndiaEvery part of this plant possesses its specific medicinal prop-erties and is usedmainly in ayurveda to fight against intestinalworms in domestic and grazing animals when administeredwith jaggeryHowever only a few reports are attributed to thisplant and its different parts and there is a large scope for inves-tigation Hence it is required to explore more of its potentialwithin the field of medicinal and pharmaceutical sciences fornovel and fruitful application of this plant in form of naturalformulation Along with this medicinal importance thisplant is used against human pathogens including H pylorianti-inflammatory activity antioxidant antiradical proteininhibition hepatoprotective antiallergic anti-HIV activityand many more Phytochemical investigation revealed that alarge number phenol derivatives and several miscellaneouscompounds from different classes have been isolated fromthis species The phenols diterpenoids steroids flavonoidscardenolides triterpenoids coumarins and isocoumarinsare mostly distributed in all parts of the plant The othermajor isolated pure compounds from this species mostlybelong to phenolic group exhibiting most of the biologicalactivity Various types of extracts from different parts andsingle compounds derived from this species have beenfound to possess biological activities including antioxidantantimicrobial anti-inflammatory cytotoxicity and immunemodulatory Fruit and bark of plant contain condensed tan-nins responsible for antioxidant activity Somenovel chalconederivatives mallotophilippens C D and E were isolatedfrom the fruits of M philippinensis Mallotoxin or rottlerinhas great anticancerous potential Among the ever-anticanceragents rottlerin appears to have great potentiality for beingused in chemotherapy Rottlerin will become a potentialmolecule for research in future to treat cancerous cell as itwill affect cell machineries involved in apoptosis survivaland autophage This suggests the view that this species haspotential to be a beneficial chemotherapeutic remedy

Although the data and other reports provided that thismedicinal plant is of great biological use in different phar-macological activities including anticancer further researchis needed in different areas regarding the toxicity and efficacyof pure phytochemicals isolated from different parts of thisplant More data will be needed from preclinical and clinicalstudies on humans to clarify its potency and safety aslack of knowledge with respect to its adverse effects andmethodological accuracy in the literature limits towardsits standardized formulation Furthermore the mechanismof action of the phytochemicals and extract of Mallotusphilippinensis is unclear more exhaustive studies will beperformed to explore its mechanism and structure activityrelationship among various constituents

In conclusion this review confirms the great potential ofMallotus philippinensis As very limited information is stillknown for this species it leads us to continue the study ondifferent species of Mallotus plant and its interesting phar-macological properties Further natural product chemistryof isolated moiety and its structural analysis of compounds

BioMed Research International 11

responsible for these activities will be an interesting field ofresearch

Conflict of Interests

The authors declare that there is no conflict of interests re-garding the publication of this paper

Acknowledgment

The authors gratefully acknowledge the financial supportprovided by CSIR Government of India New Delhi forawarding SRF in the form of research fellowship

References

[1] C-J Widen and H S Puri ldquoNatural occurrence and chemicalvariability of phloroglucinols inKamalardquoPlantaMedica vol 40no 3 pp 284ndash287 1980

[2] R Singh K C Singhal and N U Khan ldquoAntifilarial activity ofMallotus philippinensisLam on Setaria cervie (Nematoda Filar-ioidea) in-vitrordquo Indian Journal of Physiology andPharmacologyvol 41 no 4 pp 397ndash403 1997

[3] V P Kumar N S Chauhan H Padh and M Rajani ldquoSearchfor antibacterial and antifungal agents from selected Indianmedicinal plantsrdquo Journal of Ethnopharmacology vol 107 no2 pp 182ndash188 2006

[4] S Shrikumar and T K Ravi ldquoApproaches towards developmentand promotion of herbal drugsrdquo Pharmaceutical Reviews vol 1no 1 pp 180ndash183 2007

[5] C Orwa A Mutua and R Kindt ldquoAgroforestree Database atree reference and selection guiderdquo Version 4 0 2009

[6] K Usmanghani A Saeed and M T Alam ldquoIndusynicMedicine Karachirdquo Research Institute of Indusyunic Medicinevol 1997 pp 285ndash287 1997

[7] F Ahmad and S Hashmi ldquoAdulteration in commercial Kamila(Mallotus philippinensisMuell) an anthelmintic drug of reputerdquoHamdard Medicus vol 38 pp 62ndash67 1995

[8] K D Roberts E Weiss and T Reichstein ldquoGlycosides andaglycons CCLII Cardenolides of the seed of Mallotus philip-pinensisrdquo Helvetica Chimica Acta vol 46 pp 2886ndash2893 1963

[9] M Bandopadhyay V K Dhingra and S K Mukerjee ldquoTriter-penoid and other components of Mallotus philippinensisrdquo Phy-tochemistry vol 11 no 4 p 1511 1972

[10] S P Nair and J Madhusudana Rao ldquoKamaladiol-3-acetate fromthe stem bark of Mallotus philippinensisrdquo Phytochemistry vol32 pp 407ndash409 1993

[11] J DWansi JWandjiW A Kamdem et al ldquoTriterpenoids fromDrypetes chevalieri Beille (Euphorbiaceae)rdquo Natural ProductResearch vol 20 no 6 pp 586ndash592 2006

[12] P Castenada A Bahena and E Garcia ldquoChemical studieson Mexican plants used in traditional medicine XXIX Sec-ondary metabolites from the stem bark of Celaeno-dendronmexicanumrdquo Journal of Natural Products vol 56 pp 1575ndash15791993

[13] T Tanaka T Ito M Iinuma Y Takahashi and H NaganawaldquoDimeric chalcone derivatives from Mallotus philippinensisrdquoPhytochemistry vol 48 no 8 pp 1423ndash1427 1998

[14] T M Nguyen V M Chau V K Phan et al ldquoStudy on chemicalconstituents of the leaves of Mallotus philippinensisrdquo Tap ChiHoa Hoc vol 48 pp 352ndash357 2010

[15] M Furusawa Y Ido T Tanaka et al ldquoNovel complex flavonoidsfrom Mallotus philippinensis (Kamala tree)rdquo Helvetica ChimicaActa vol 88 no 5 pp 1048ndash1058 2005

[16] M Lounasmaa C J Widen C M Tuuf and A HuhtikangasldquoOn the phloroglucinol derivatives of Mallotus philippinensisrdquoPlanta Medica vol 28 no 1 pp 16ndash31 1975

[17] S F H Zaidi I Yoshida F Butt et al ldquoPotent bactericidal con-stituents from Mallotus philippinensis against clarithromycinand metronidazole resistant strains of Japanese and Pakistanihelicobacter pylorirdquo Biological and Pharmaceutical Bulletin vol32 no 4 pp 631ndash636 2009

[18] M Arfan H Amin M Karamac et al ldquoAntioxidant activityof extracts of Mallotus philippinensis fruit and barkrdquo Journal ofFood Lipids vol 14 no 3 pp 280ndash297 2007

[19] M Arfan K Hazrat and K Magdalena ldquoAntioxidant activityof phenolic fractions of Mallotus philippinensis bark extractrdquoJournal of Food Science vol 27 no 2 pp 109ndash117 2009

[20] R Saijo G Nonaka and I Nishioka ldquoTannins and related com-pounds LXXXVIII Isolation and characterization of hydrolyz-able tannins fromMallotus japonicus (Thunb)Mueller-Arg andM philippinensis (Lam)Mueller-ArgrdquoChemical amp Pharmaceu-tical Bulletin vol 37 no 11 pp 2940ndash2947 1989

[21] S C Gupta S S Gupta and J S Aggarwal ldquoChemical exami-nation of the seeds of Mallotus philippinensis III Constitutionof kamlolenic acid isolated from the oilrdquo Journal of Scientific ampIndustrial Research vol 12 pp 240ndash242 1953

[22] S C Thakur S S Thakur S K Chaube and S P Singh ldquoAnetheral extract of Kamala (Mallotus philippinensis (Moll Arg)Lam) seed induce adverse effects on reproductive parametersof female ratsrdquo Reproductive Toxicology vol 20 no 1 pp 149ndash156 2005

[23] M L Gujral D R Varma K N Sareen and A K Roy ldquoOralcontraceptives II Antifertility effect ofMallotus philippinensisrdquoIndian Journal of Medical Research vol 48 pp 52ndash58 1960

[24] KMoorthy K Srinivasan C Subramanian CMohanasundariand M Palaniswamy ldquoPhyto-chemical screening and antibac-terial evaluation of stem bark of Mallotus philippinensis varTomentosusrdquoAfrican Journal of Biotechnology vol 6 no 13 pp1521ndash1523 2007

[25] M Gangwar D Kumar R Tilak et al ldquoQualitative phy-tochemical characterization and antibacterial evaluation ofglandular hairs ofMallotus philippinensis fruit extractrdquo Journalof Pharmacy Research vol 4 no 11 pp 4214ndash4216 2011

[26] A Daikonya S Katsuki and S Kitanaka ldquoAntiallergic agentsfrom naturalsources 9 Inhibition of nitric oxide productionby novel chalcone derivatives from Mallotus philippinensis(Euphorbiaceae)rdquo Chemical amp Pharmaceutical Bulletin vol 52no 11 pp 1326ndash1329 2004

[27] M Gschwendt H J Muller K Kielbassa et al ldquoRottlerina novel protein kinase inhibitorrdquo Biochemical and BiophysicalResearch Communications vol 199 no 1 pp 93ndash98 1994

[28] Y F Liao Y C Hung W H Chang et al ldquoThe PKC deltainhibitor rottlerin induces apoptosis of haematopoietic celllines through mitochondrial membrane depolarization andcaspasescascaderdquo Life Sciences vol 77 no 6 pp 707ndash719 2005

[29] H S Kang E K Park K H Kim et al ldquoReceptor activatorof nuclear factor-kappa B is induced by a rottlerin-sensitiveand p38 MAP kinase-dependent pathway during monocytedifferentiationrdquoMolecules and Cells vol 17 no 3 pp 438ndash4452004

12 BioMed Research International

[30] S P Soltoff ldquoRottlerin an inappropriate and ineffectiveinhibitor of PKC120575rdquo Trends in Pharmacological Sciences vol 28no 9 pp 453ndash458 2007

[31] Y Choi D K Kim S S Kang J K Sonn and E J Jin ldquoIntegrinsignaling and cell spreading alterations by rottlerin treatment ofchick limb bud mesenchymal cellsrdquo Biochimie vol 91 no 5 pp624ndash631 2009

[32] C Springael S Thomas S Rahmouni et al ldquoRottlerin inhibitshuman T cell responsesrdquo Biochemical Pharmacology vol 73 no4 pp 515ndash525 2007

[33] J H Choi Y P Hwang E H Han et al ldquoInhibition of acrolein-stimulated MUC5AC expression by Platycodon grandiflorumroot-derived saponin in A549 cellsrdquo Food and Chemical Toxi-cology vol 49 no 9 pp 2157ndash2166 2011

[34] E L M Guimaraes C Empsen A Geerts and L A vanGrunsven ldquoAdvanced glycation end products induce produc-tion of reactive oxygen species via the activation of NADPHoxidase in murine hepatic stellate cellsrdquo Journal of Hepatologyvol 52 no 3 pp 389ndash397 2010

[35] H Mizuguchi T Terao M Kitai et al ldquoInvolvement of pro-tein kinase C120575extracellular signal-regulated kinasepoly(ADP-ribose) polymerase-1 (PARP-1) signaling pathway in histamine-induced up-regulation of histamine H1 receptor gene expres-sion in HeLa cellsrdquo Journal of Biological Chemistry vol 286 no35 pp 30542ndash30551 2011

[36] S Ramakrishna K M Geetha P V V S Bhaskar gopalR P Kumar C P Madav and L Umachandar ldquoEffect ofMallotus PhilippinensisMuell-Arg leaves against hepatotoxicityof Carbon tetrachloride in ratsrdquo International Journal of Phar-maceutical Sciences and Research vol 2 pp 74ndash83 2011

[37] V Sharma ldquoA polyphenolic compound rottlerin demonstratessignificant in vitro cytotoxicity against human cancer celllines isolation and characterization from the fruits ofMallotusphilippinensisrdquo Journal of Plant Biochemistry and Biotechnologyvol 20 no 2 pp 190ndash195 2011

[38] M S Akhtar and I Ahmad ldquoComparative efficacy of Mallotusphilippinensis fruit (Kamala) or Nilzan drug against gastroin-testinal cestodes in Beetal goatsrdquo Small Ruminant Research vol8 no 1-2 pp 121ndash128 1992

[39] A Jabbar M A Raza Z Iqbal and M N Khan ldquoAn inventoryof the ethnobotanicals used as anthelmintics in the southernPunjab (Pakistan)rdquo Journal of Ethnopharmacology vol 108 no1 pp 152ndash154 2006

[40] M Gangwar A Dalai A Chaudhary et al ldquoStudy on activityof alcoholic extract of glands and hairs of fruits of Mallotusphilippinensis in murine cestodal infection modelrdquo Interna-tional Journal of Pharmacy amp Pharmaceutical Sciences vol 4no 1 pp 643ndash645 2012

[41] M Gangwar V C Verma T D Singh S K Singh R KGoel and G Nath ldquoIn-vitro scolicidal activity of Mallotusphilippinensis (Lam) Muell Arg fruit glandular hair extractagainst hydatid cyst Echinococcus granulosusrdquo Asian PacificJournal of Tropical Medicine vol 6 no 8 pp 595ndash601 2013

[42] S S Gupta P Verma and K Hishikar ldquoPurgative andanthelmintic effects of Mallotus philippinensis in rats againsttape wormrdquo Indian Journal of Physiology amp Pharmacology vol28 no 1 pp 63ndash66 1984

[43] A Hussain M N Khan Z Iqbal and M S Sajid ldquoAn accountof the botanical anthelmintics used in traditional veterinarypractices in Sahiwal district of Punjab Pakistanrdquo Journal ofEthnopharmacology vol 119 no 1 pp 185ndash190 2008

[44] Q Hong D E Minter S G Franzblau M Arfan H Amin andM G Reinecke ldquoAnti-tuberculosis compounds from Mallotusphilippinensisrdquo Natural Product Communications vol 5 no 2pp 211ndash217 2010

[45] V K Gupta C Shukla G R S Bisht D Saikia S Kumarand R L Thakur ldquoDetection of anti-tuberculosis activity insome folklore plants by radiometric BACTEC assayrdquo Letters inApplied Microbiology vol 52 no 1 pp 33ndash40 2011

[46] R Tanaka T Nakata C Yamaguchi S Wada T Yamadaand H Tokuda ldquoPotential anti-tumor-promoting activity of3120572-Hydroxy-D a-friedooleanan-2-one from the stem bark ofMallotus philippinensisrdquo Planta Medica vol 74 no 4 pp 413ndash416 2008

[47] A Daikonya S Katsuki J B Wu and S Kitanaka ldquoAnti-allergic agents from natural sources (4) anti-allergic activityof new phloroglucinol derivatives from Mallotus philippinensis(Euphorbiaceae)rdquo Chemical and Pharmaceutical Bulletin vol50 no 12 pp 1566ndash1569 2002

[48] T K Chan S W David C Cheng S P Guan H MKoh and W S Wong ldquoAnti-allergic actions of rottlerin fromMallotus philippinensisis in experimental mast cell-mediatedanaphylactic modelsrdquo Phytomedicine vol 20 no 10 pp 853ndash860 2013

[49] M Khan R A Qureshi M Hussain K Mehmood and R AKhan ldquoHexane soluble extract ofMallotus philippinensis (Lam)Muell Arg root possesses anti-leukaemic activityrdquo ChemistryCentral Journal vol 7 no 1 article 157 2013

[50] R Roshan S G Kulkarni S P Tupe et al ldquoAntifungal dimericchalcone derivative kamalachalcone E from Mallotus philip-pinensisrdquo Natural Product Research Formerly Natural ProductLetters vol 28 no 4 pp 245ndash250 2014

[51] H Nakane M Arisawa A Fujita S Koshimura and KOno ldquoInhibition of HIV-reverse transcriptase activity by somephloroglucinol derivativesrdquo FEBS Letters vol 286 no 1-2 pp83ndash85 1991

[52] T Furumoto N Ozawa Y Inami et al ldquoMallotus philippinensisbark extracts promote preferential migration of mesenchymalstem cells and improve wound healing in micerdquo Phytomedicinevol 21 no 3 pp 247ndash253 2014

[53] Maeda ldquoMethod for producing Mallotus philippinensis dyecomposition and the compositionrdquo US7556829 B2 2009

[54] C Wiart Medicinal Plants of the Asia-Pacific Drugs for theFutureWorld Scientific Singapore 2006

[55] V R Sharma ldquoA review on endangered plant of Mallotusphilippinensis (Lam) MArgrdquo Pharmacologyonline vol 3 pp1256ndash1265 2011

[56] V Tangpu T Temjenmongla and A K Yadav ldquoAnticestodalproperty of Strobilanthes discolor an experimental study inHymenolepis diminutamdashratmodelrdquo Journal of Ethnopharmacol-ogy vol 105 no 3 pp 459ndash463 2006

[57] V Tangpu K Temjenmongla and A K Yadav ldquoAnticestodalactivity ofTrifolium repens extractrdquo Pharmaceutical Biology vol42 no 8 pp 656ndash658 2004

[58] A K Yadav and T Temjenmongla ldquoAnticestodal activity ofHouttuynia cordata leaf extract againstHymenolepis diminuta inexperimentally infected ratsrdquo Journal of Parasitic Diseases vol35 no 2 pp 190ndash194 2011

[59] T Temjenmongla and A K Yadav ldquoAnticestodal efficacy ofLasia spinosa extract against experimental Hymenolepis dimin-uta infections in ratsrdquo Pharmaceutical Biology vol 44 no 7 pp499ndash502 2006

BioMed Research International 13

[60] M L Dhar M M Dhar B N Dhawan B N Mehrotra and CRay ldquoScreening of Indian plants for biological activityrdquo IndianJournal of Experimental Biology vol 6 no 4 pp 232ndash247 1968

[61] Temjenmongla and A K Yadav ldquoAnticestodal efficacy offolklore medicinal plants of Naga tribes in north-east IndiardquoAfrican Journal of Traditional Complementary and AlternativeMedicines vol 2 pp 129ndash133 2005

[62] T V Tangpu and A K Yadav ldquoAnticestodal efficacy of Psidiumguajava against experimental Hymenolepis diminuta infectionin ratsrdquo Indian Journal of Pharmacology vol 38 no 1 pp 29ndash32 2006

[63] R Singh A Mehta P Mehta and K Shukla ldquoAnthelminticactivity of Rhizome extracts of Curcuma longa and Zingiberofficinalerdquo International Journal of Pharmacy and Pharmaceu-tical Sciences vol 3 no 2 pp 236ndash237 2011

[64] M K Asha D Prashanth B Murali R Padmaja and A AmitldquoAnthelmintic activity of essential oil of Ocimum sanctum andeugenolrdquo Fitoterapia vol 72 no 6 pp 669ndash670 2001

[65] J B Githiori J Hoglund P J Waller and R L Baker ldquoTheanthelmintic efficacy of the plantAlbizia anthelmintica againstthe nematode parasites Haemonchus contortus of sheep andHeligmosomoides polygyrus of micerdquo Veterinary Parasitologyvol 116 no 1 pp 23ndash34 2003

[66] N M Enwerema J I Okoguna C O Wambebea D A Oko-rieb and P A Akahc ldquoAnthelmintic activity of the stem barkextracts of Berlina grandiflora and one of its active principlesBetulinic acidrdquo Phytomedicine vol 8 pp 112ndash114 2001

[67] Z Iqbal M Lateef A Jabber M N Ghayur and A HGilani ldquoIn vitro and in vivo anthelmintic activity of Nicotianatabacum L leaves against gastrointestinal nematodes of sheeprdquoPhytotherapy Research vol 20 no 1 pp 46ndash48 2006

[68] Z Iqbal M Lateef A Jabbar G Muhammad and M N KhanldquoAnthelmintic activity of Calotropis procera (Ait) Ait F flowersin sheeprdquo Journal of Ethnopharmacology vol 102 no 2 pp 256ndash261 2005

Submit your manuscripts athttpwwwhindawicom

PainResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom

Volume 2014

ToxinsJournal of

VaccinesJournal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AntibioticsInternational Journal of

ToxicologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

StrokeResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Drug DeliveryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in Pharmacological Sciences

Tropical MedicineJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AddictionJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

Emergency Medicine InternationalHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Autoimmune Diseases

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Anesthesiology Research and Practice

ScientificaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Pharmaceutics

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Page 11: Mallotus philippinensis Muell. Arg (Euphorbiaceae ...

BioMed Research International 11

responsible for these activities will be an interesting field ofresearch

Conflict of Interests

The authors declare that there is no conflict of interests re-garding the publication of this paper

Acknowledgment

The authors gratefully acknowledge the financial supportprovided by CSIR Government of India New Delhi forawarding SRF in the form of research fellowship

References

[1] C-J Widen and H S Puri ldquoNatural occurrence and chemicalvariability of phloroglucinols inKamalardquoPlantaMedica vol 40no 3 pp 284ndash287 1980

[2] R Singh K C Singhal and N U Khan ldquoAntifilarial activity ofMallotus philippinensisLam on Setaria cervie (Nematoda Filar-ioidea) in-vitrordquo Indian Journal of Physiology andPharmacologyvol 41 no 4 pp 397ndash403 1997

[3] V P Kumar N S Chauhan H Padh and M Rajani ldquoSearchfor antibacterial and antifungal agents from selected Indianmedicinal plantsrdquo Journal of Ethnopharmacology vol 107 no2 pp 182ndash188 2006

[4] S Shrikumar and T K Ravi ldquoApproaches towards developmentand promotion of herbal drugsrdquo Pharmaceutical Reviews vol 1no 1 pp 180ndash183 2007

[5] C Orwa A Mutua and R Kindt ldquoAgroforestree Database atree reference and selection guiderdquo Version 4 0 2009

[6] K Usmanghani A Saeed and M T Alam ldquoIndusynicMedicine Karachirdquo Research Institute of Indusyunic Medicinevol 1997 pp 285ndash287 1997

[7] F Ahmad and S Hashmi ldquoAdulteration in commercial Kamila(Mallotus philippinensisMuell) an anthelmintic drug of reputerdquoHamdard Medicus vol 38 pp 62ndash67 1995

[8] K D Roberts E Weiss and T Reichstein ldquoGlycosides andaglycons CCLII Cardenolides of the seed of Mallotus philip-pinensisrdquo Helvetica Chimica Acta vol 46 pp 2886ndash2893 1963

[9] M Bandopadhyay V K Dhingra and S K Mukerjee ldquoTriter-penoid and other components of Mallotus philippinensisrdquo Phy-tochemistry vol 11 no 4 p 1511 1972

[10] S P Nair and J Madhusudana Rao ldquoKamaladiol-3-acetate fromthe stem bark of Mallotus philippinensisrdquo Phytochemistry vol32 pp 407ndash409 1993

[11] J DWansi JWandjiW A Kamdem et al ldquoTriterpenoids fromDrypetes chevalieri Beille (Euphorbiaceae)rdquo Natural ProductResearch vol 20 no 6 pp 586ndash592 2006

[12] P Castenada A Bahena and E Garcia ldquoChemical studieson Mexican plants used in traditional medicine XXIX Sec-ondary metabolites from the stem bark of Celaeno-dendronmexicanumrdquo Journal of Natural Products vol 56 pp 1575ndash15791993

[13] T Tanaka T Ito M Iinuma Y Takahashi and H NaganawaldquoDimeric chalcone derivatives from Mallotus philippinensisrdquoPhytochemistry vol 48 no 8 pp 1423ndash1427 1998

[14] T M Nguyen V M Chau V K Phan et al ldquoStudy on chemicalconstituents of the leaves of Mallotus philippinensisrdquo Tap ChiHoa Hoc vol 48 pp 352ndash357 2010

[15] M Furusawa Y Ido T Tanaka et al ldquoNovel complex flavonoidsfrom Mallotus philippinensis (Kamala tree)rdquo Helvetica ChimicaActa vol 88 no 5 pp 1048ndash1058 2005

[16] M Lounasmaa C J Widen C M Tuuf and A HuhtikangasldquoOn the phloroglucinol derivatives of Mallotus philippinensisrdquoPlanta Medica vol 28 no 1 pp 16ndash31 1975

[17] S F H Zaidi I Yoshida F Butt et al ldquoPotent bactericidal con-stituents from Mallotus philippinensis against clarithromycinand metronidazole resistant strains of Japanese and Pakistanihelicobacter pylorirdquo Biological and Pharmaceutical Bulletin vol32 no 4 pp 631ndash636 2009

[18] M Arfan H Amin M Karamac et al ldquoAntioxidant activityof extracts of Mallotus philippinensis fruit and barkrdquo Journal ofFood Lipids vol 14 no 3 pp 280ndash297 2007

[19] M Arfan K Hazrat and K Magdalena ldquoAntioxidant activityof phenolic fractions of Mallotus philippinensis bark extractrdquoJournal of Food Science vol 27 no 2 pp 109ndash117 2009

[20] R Saijo G Nonaka and I Nishioka ldquoTannins and related com-pounds LXXXVIII Isolation and characterization of hydrolyz-able tannins fromMallotus japonicus (Thunb)Mueller-Arg andM philippinensis (Lam)Mueller-ArgrdquoChemical amp Pharmaceu-tical Bulletin vol 37 no 11 pp 2940ndash2947 1989

[21] S C Gupta S S Gupta and J S Aggarwal ldquoChemical exami-nation of the seeds of Mallotus philippinensis III Constitutionof kamlolenic acid isolated from the oilrdquo Journal of Scientific ampIndustrial Research vol 12 pp 240ndash242 1953

[22] S C Thakur S S Thakur S K Chaube and S P Singh ldquoAnetheral extract of Kamala (Mallotus philippinensis (Moll Arg)Lam) seed induce adverse effects on reproductive parametersof female ratsrdquo Reproductive Toxicology vol 20 no 1 pp 149ndash156 2005

[23] M L Gujral D R Varma K N Sareen and A K Roy ldquoOralcontraceptives II Antifertility effect ofMallotus philippinensisrdquoIndian Journal of Medical Research vol 48 pp 52ndash58 1960

[24] KMoorthy K Srinivasan C Subramanian CMohanasundariand M Palaniswamy ldquoPhyto-chemical screening and antibac-terial evaluation of stem bark of Mallotus philippinensis varTomentosusrdquoAfrican Journal of Biotechnology vol 6 no 13 pp1521ndash1523 2007

[25] M Gangwar D Kumar R Tilak et al ldquoQualitative phy-tochemical characterization and antibacterial evaluation ofglandular hairs ofMallotus philippinensis fruit extractrdquo Journalof Pharmacy Research vol 4 no 11 pp 4214ndash4216 2011

[26] A Daikonya S Katsuki and S Kitanaka ldquoAntiallergic agentsfrom naturalsources 9 Inhibition of nitric oxide productionby novel chalcone derivatives from Mallotus philippinensis(Euphorbiaceae)rdquo Chemical amp Pharmaceutical Bulletin vol 52no 11 pp 1326ndash1329 2004

[27] M Gschwendt H J Muller K Kielbassa et al ldquoRottlerina novel protein kinase inhibitorrdquo Biochemical and BiophysicalResearch Communications vol 199 no 1 pp 93ndash98 1994

[28] Y F Liao Y C Hung W H Chang et al ldquoThe PKC deltainhibitor rottlerin induces apoptosis of haematopoietic celllines through mitochondrial membrane depolarization andcaspasescascaderdquo Life Sciences vol 77 no 6 pp 707ndash719 2005

[29] H S Kang E K Park K H Kim et al ldquoReceptor activatorof nuclear factor-kappa B is induced by a rottlerin-sensitiveand p38 MAP kinase-dependent pathway during monocytedifferentiationrdquoMolecules and Cells vol 17 no 3 pp 438ndash4452004

12 BioMed Research International

[30] S P Soltoff ldquoRottlerin an inappropriate and ineffectiveinhibitor of PKC120575rdquo Trends in Pharmacological Sciences vol 28no 9 pp 453ndash458 2007

[31] Y Choi D K Kim S S Kang J K Sonn and E J Jin ldquoIntegrinsignaling and cell spreading alterations by rottlerin treatment ofchick limb bud mesenchymal cellsrdquo Biochimie vol 91 no 5 pp624ndash631 2009

[32] C Springael S Thomas S Rahmouni et al ldquoRottlerin inhibitshuman T cell responsesrdquo Biochemical Pharmacology vol 73 no4 pp 515ndash525 2007

[33] J H Choi Y P Hwang E H Han et al ldquoInhibition of acrolein-stimulated MUC5AC expression by Platycodon grandiflorumroot-derived saponin in A549 cellsrdquo Food and Chemical Toxi-cology vol 49 no 9 pp 2157ndash2166 2011

[34] E L M Guimaraes C Empsen A Geerts and L A vanGrunsven ldquoAdvanced glycation end products induce produc-tion of reactive oxygen species via the activation of NADPHoxidase in murine hepatic stellate cellsrdquo Journal of Hepatologyvol 52 no 3 pp 389ndash397 2010

[35] H Mizuguchi T Terao M Kitai et al ldquoInvolvement of pro-tein kinase C120575extracellular signal-regulated kinasepoly(ADP-ribose) polymerase-1 (PARP-1) signaling pathway in histamine-induced up-regulation of histamine H1 receptor gene expres-sion in HeLa cellsrdquo Journal of Biological Chemistry vol 286 no35 pp 30542ndash30551 2011

[36] S Ramakrishna K M Geetha P V V S Bhaskar gopalR P Kumar C P Madav and L Umachandar ldquoEffect ofMallotus PhilippinensisMuell-Arg leaves against hepatotoxicityof Carbon tetrachloride in ratsrdquo International Journal of Phar-maceutical Sciences and Research vol 2 pp 74ndash83 2011

[37] V Sharma ldquoA polyphenolic compound rottlerin demonstratessignificant in vitro cytotoxicity against human cancer celllines isolation and characterization from the fruits ofMallotusphilippinensisrdquo Journal of Plant Biochemistry and Biotechnologyvol 20 no 2 pp 190ndash195 2011

[38] M S Akhtar and I Ahmad ldquoComparative efficacy of Mallotusphilippinensis fruit (Kamala) or Nilzan drug against gastroin-testinal cestodes in Beetal goatsrdquo Small Ruminant Research vol8 no 1-2 pp 121ndash128 1992

[39] A Jabbar M A Raza Z Iqbal and M N Khan ldquoAn inventoryof the ethnobotanicals used as anthelmintics in the southernPunjab (Pakistan)rdquo Journal of Ethnopharmacology vol 108 no1 pp 152ndash154 2006

[40] M Gangwar A Dalai A Chaudhary et al ldquoStudy on activityof alcoholic extract of glands and hairs of fruits of Mallotusphilippinensis in murine cestodal infection modelrdquo Interna-tional Journal of Pharmacy amp Pharmaceutical Sciences vol 4no 1 pp 643ndash645 2012

[41] M Gangwar V C Verma T D Singh S K Singh R KGoel and G Nath ldquoIn-vitro scolicidal activity of Mallotusphilippinensis (Lam) Muell Arg fruit glandular hair extractagainst hydatid cyst Echinococcus granulosusrdquo Asian PacificJournal of Tropical Medicine vol 6 no 8 pp 595ndash601 2013

[42] S S Gupta P Verma and K Hishikar ldquoPurgative andanthelmintic effects of Mallotus philippinensis in rats againsttape wormrdquo Indian Journal of Physiology amp Pharmacology vol28 no 1 pp 63ndash66 1984

[43] A Hussain M N Khan Z Iqbal and M S Sajid ldquoAn accountof the botanical anthelmintics used in traditional veterinarypractices in Sahiwal district of Punjab Pakistanrdquo Journal ofEthnopharmacology vol 119 no 1 pp 185ndash190 2008

[44] Q Hong D E Minter S G Franzblau M Arfan H Amin andM G Reinecke ldquoAnti-tuberculosis compounds from Mallotusphilippinensisrdquo Natural Product Communications vol 5 no 2pp 211ndash217 2010

[45] V K Gupta C Shukla G R S Bisht D Saikia S Kumarand R L Thakur ldquoDetection of anti-tuberculosis activity insome folklore plants by radiometric BACTEC assayrdquo Letters inApplied Microbiology vol 52 no 1 pp 33ndash40 2011

[46] R Tanaka T Nakata C Yamaguchi S Wada T Yamadaand H Tokuda ldquoPotential anti-tumor-promoting activity of3120572-Hydroxy-D a-friedooleanan-2-one from the stem bark ofMallotus philippinensisrdquo Planta Medica vol 74 no 4 pp 413ndash416 2008

[47] A Daikonya S Katsuki J B Wu and S Kitanaka ldquoAnti-allergic agents from natural sources (4) anti-allergic activityof new phloroglucinol derivatives from Mallotus philippinensis(Euphorbiaceae)rdquo Chemical and Pharmaceutical Bulletin vol50 no 12 pp 1566ndash1569 2002

[48] T K Chan S W David C Cheng S P Guan H MKoh and W S Wong ldquoAnti-allergic actions of rottlerin fromMallotus philippinensisis in experimental mast cell-mediatedanaphylactic modelsrdquo Phytomedicine vol 20 no 10 pp 853ndash860 2013

[49] M Khan R A Qureshi M Hussain K Mehmood and R AKhan ldquoHexane soluble extract ofMallotus philippinensis (Lam)Muell Arg root possesses anti-leukaemic activityrdquo ChemistryCentral Journal vol 7 no 1 article 157 2013

[50] R Roshan S G Kulkarni S P Tupe et al ldquoAntifungal dimericchalcone derivative kamalachalcone E from Mallotus philip-pinensisrdquo Natural Product Research Formerly Natural ProductLetters vol 28 no 4 pp 245ndash250 2014

[51] H Nakane M Arisawa A Fujita S Koshimura and KOno ldquoInhibition of HIV-reverse transcriptase activity by somephloroglucinol derivativesrdquo FEBS Letters vol 286 no 1-2 pp83ndash85 1991

[52] T Furumoto N Ozawa Y Inami et al ldquoMallotus philippinensisbark extracts promote preferential migration of mesenchymalstem cells and improve wound healing in micerdquo Phytomedicinevol 21 no 3 pp 247ndash253 2014

[53] Maeda ldquoMethod for producing Mallotus philippinensis dyecomposition and the compositionrdquo US7556829 B2 2009

[54] C Wiart Medicinal Plants of the Asia-Pacific Drugs for theFutureWorld Scientific Singapore 2006

[55] V R Sharma ldquoA review on endangered plant of Mallotusphilippinensis (Lam) MArgrdquo Pharmacologyonline vol 3 pp1256ndash1265 2011

[56] V Tangpu T Temjenmongla and A K Yadav ldquoAnticestodalproperty of Strobilanthes discolor an experimental study inHymenolepis diminutamdashratmodelrdquo Journal of Ethnopharmacol-ogy vol 105 no 3 pp 459ndash463 2006

[57] V Tangpu K Temjenmongla and A K Yadav ldquoAnticestodalactivity ofTrifolium repens extractrdquo Pharmaceutical Biology vol42 no 8 pp 656ndash658 2004

[58] A K Yadav and T Temjenmongla ldquoAnticestodal activity ofHouttuynia cordata leaf extract againstHymenolepis diminuta inexperimentally infected ratsrdquo Journal of Parasitic Diseases vol35 no 2 pp 190ndash194 2011

[59] T Temjenmongla and A K Yadav ldquoAnticestodal efficacy ofLasia spinosa extract against experimental Hymenolepis dimin-uta infections in ratsrdquo Pharmaceutical Biology vol 44 no 7 pp499ndash502 2006

BioMed Research International 13

[60] M L Dhar M M Dhar B N Dhawan B N Mehrotra and CRay ldquoScreening of Indian plants for biological activityrdquo IndianJournal of Experimental Biology vol 6 no 4 pp 232ndash247 1968

[61] Temjenmongla and A K Yadav ldquoAnticestodal efficacy offolklore medicinal plants of Naga tribes in north-east IndiardquoAfrican Journal of Traditional Complementary and AlternativeMedicines vol 2 pp 129ndash133 2005

[62] T V Tangpu and A K Yadav ldquoAnticestodal efficacy of Psidiumguajava against experimental Hymenolepis diminuta infectionin ratsrdquo Indian Journal of Pharmacology vol 38 no 1 pp 29ndash32 2006

[63] R Singh A Mehta P Mehta and K Shukla ldquoAnthelminticactivity of Rhizome extracts of Curcuma longa and Zingiberofficinalerdquo International Journal of Pharmacy and Pharmaceu-tical Sciences vol 3 no 2 pp 236ndash237 2011

[64] M K Asha D Prashanth B Murali R Padmaja and A AmitldquoAnthelmintic activity of essential oil of Ocimum sanctum andeugenolrdquo Fitoterapia vol 72 no 6 pp 669ndash670 2001

[65] J B Githiori J Hoglund P J Waller and R L Baker ldquoTheanthelmintic efficacy of the plantAlbizia anthelmintica againstthe nematode parasites Haemonchus contortus of sheep andHeligmosomoides polygyrus of micerdquo Veterinary Parasitologyvol 116 no 1 pp 23ndash34 2003

[66] N M Enwerema J I Okoguna C O Wambebea D A Oko-rieb and P A Akahc ldquoAnthelmintic activity of the stem barkextracts of Berlina grandiflora and one of its active principlesBetulinic acidrdquo Phytomedicine vol 8 pp 112ndash114 2001

[67] Z Iqbal M Lateef A Jabber M N Ghayur and A HGilani ldquoIn vitro and in vivo anthelmintic activity of Nicotianatabacum L leaves against gastrointestinal nematodes of sheeprdquoPhytotherapy Research vol 20 no 1 pp 46ndash48 2006

[68] Z Iqbal M Lateef A Jabbar G Muhammad and M N KhanldquoAnthelmintic activity of Calotropis procera (Ait) Ait F flowersin sheeprdquo Journal of Ethnopharmacology vol 102 no 2 pp 256ndash261 2005

Submit your manuscripts athttpwwwhindawicom

PainResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom

Volume 2014

ToxinsJournal of

VaccinesJournal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AntibioticsInternational Journal of

ToxicologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

StrokeResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Drug DeliveryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in Pharmacological Sciences

Tropical MedicineJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AddictionJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

Emergency Medicine InternationalHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Autoimmune Diseases

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Anesthesiology Research and Practice

ScientificaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Pharmaceutics

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Page 12: Mallotus philippinensis Muell. Arg (Euphorbiaceae ...

12 BioMed Research International

[30] S P Soltoff ldquoRottlerin an inappropriate and ineffectiveinhibitor of PKC120575rdquo Trends in Pharmacological Sciences vol 28no 9 pp 453ndash458 2007

[31] Y Choi D K Kim S S Kang J K Sonn and E J Jin ldquoIntegrinsignaling and cell spreading alterations by rottlerin treatment ofchick limb bud mesenchymal cellsrdquo Biochimie vol 91 no 5 pp624ndash631 2009

[32] C Springael S Thomas S Rahmouni et al ldquoRottlerin inhibitshuman T cell responsesrdquo Biochemical Pharmacology vol 73 no4 pp 515ndash525 2007

[33] J H Choi Y P Hwang E H Han et al ldquoInhibition of acrolein-stimulated MUC5AC expression by Platycodon grandiflorumroot-derived saponin in A549 cellsrdquo Food and Chemical Toxi-cology vol 49 no 9 pp 2157ndash2166 2011

[34] E L M Guimaraes C Empsen A Geerts and L A vanGrunsven ldquoAdvanced glycation end products induce produc-tion of reactive oxygen species via the activation of NADPHoxidase in murine hepatic stellate cellsrdquo Journal of Hepatologyvol 52 no 3 pp 389ndash397 2010

[35] H Mizuguchi T Terao M Kitai et al ldquoInvolvement of pro-tein kinase C120575extracellular signal-regulated kinasepoly(ADP-ribose) polymerase-1 (PARP-1) signaling pathway in histamine-induced up-regulation of histamine H1 receptor gene expres-sion in HeLa cellsrdquo Journal of Biological Chemistry vol 286 no35 pp 30542ndash30551 2011

[36] S Ramakrishna K M Geetha P V V S Bhaskar gopalR P Kumar C P Madav and L Umachandar ldquoEffect ofMallotus PhilippinensisMuell-Arg leaves against hepatotoxicityof Carbon tetrachloride in ratsrdquo International Journal of Phar-maceutical Sciences and Research vol 2 pp 74ndash83 2011

[37] V Sharma ldquoA polyphenolic compound rottlerin demonstratessignificant in vitro cytotoxicity against human cancer celllines isolation and characterization from the fruits ofMallotusphilippinensisrdquo Journal of Plant Biochemistry and Biotechnologyvol 20 no 2 pp 190ndash195 2011

[38] M S Akhtar and I Ahmad ldquoComparative efficacy of Mallotusphilippinensis fruit (Kamala) or Nilzan drug against gastroin-testinal cestodes in Beetal goatsrdquo Small Ruminant Research vol8 no 1-2 pp 121ndash128 1992

[39] A Jabbar M A Raza Z Iqbal and M N Khan ldquoAn inventoryof the ethnobotanicals used as anthelmintics in the southernPunjab (Pakistan)rdquo Journal of Ethnopharmacology vol 108 no1 pp 152ndash154 2006

[40] M Gangwar A Dalai A Chaudhary et al ldquoStudy on activityof alcoholic extract of glands and hairs of fruits of Mallotusphilippinensis in murine cestodal infection modelrdquo Interna-tional Journal of Pharmacy amp Pharmaceutical Sciences vol 4no 1 pp 643ndash645 2012

[41] M Gangwar V C Verma T D Singh S K Singh R KGoel and G Nath ldquoIn-vitro scolicidal activity of Mallotusphilippinensis (Lam) Muell Arg fruit glandular hair extractagainst hydatid cyst Echinococcus granulosusrdquo Asian PacificJournal of Tropical Medicine vol 6 no 8 pp 595ndash601 2013

[42] S S Gupta P Verma and K Hishikar ldquoPurgative andanthelmintic effects of Mallotus philippinensis in rats againsttape wormrdquo Indian Journal of Physiology amp Pharmacology vol28 no 1 pp 63ndash66 1984

[43] A Hussain M N Khan Z Iqbal and M S Sajid ldquoAn accountof the botanical anthelmintics used in traditional veterinarypractices in Sahiwal district of Punjab Pakistanrdquo Journal ofEthnopharmacology vol 119 no 1 pp 185ndash190 2008

[44] Q Hong D E Minter S G Franzblau M Arfan H Amin andM G Reinecke ldquoAnti-tuberculosis compounds from Mallotusphilippinensisrdquo Natural Product Communications vol 5 no 2pp 211ndash217 2010

[45] V K Gupta C Shukla G R S Bisht D Saikia S Kumarand R L Thakur ldquoDetection of anti-tuberculosis activity insome folklore plants by radiometric BACTEC assayrdquo Letters inApplied Microbiology vol 52 no 1 pp 33ndash40 2011

[46] R Tanaka T Nakata C Yamaguchi S Wada T Yamadaand H Tokuda ldquoPotential anti-tumor-promoting activity of3120572-Hydroxy-D a-friedooleanan-2-one from the stem bark ofMallotus philippinensisrdquo Planta Medica vol 74 no 4 pp 413ndash416 2008

[47] A Daikonya S Katsuki J B Wu and S Kitanaka ldquoAnti-allergic agents from natural sources (4) anti-allergic activityof new phloroglucinol derivatives from Mallotus philippinensis(Euphorbiaceae)rdquo Chemical and Pharmaceutical Bulletin vol50 no 12 pp 1566ndash1569 2002

[48] T K Chan S W David C Cheng S P Guan H MKoh and W S Wong ldquoAnti-allergic actions of rottlerin fromMallotus philippinensisis in experimental mast cell-mediatedanaphylactic modelsrdquo Phytomedicine vol 20 no 10 pp 853ndash860 2013

[49] M Khan R A Qureshi M Hussain K Mehmood and R AKhan ldquoHexane soluble extract ofMallotus philippinensis (Lam)Muell Arg root possesses anti-leukaemic activityrdquo ChemistryCentral Journal vol 7 no 1 article 157 2013

[50] R Roshan S G Kulkarni S P Tupe et al ldquoAntifungal dimericchalcone derivative kamalachalcone E from Mallotus philip-pinensisrdquo Natural Product Research Formerly Natural ProductLetters vol 28 no 4 pp 245ndash250 2014

[51] H Nakane M Arisawa A Fujita S Koshimura and KOno ldquoInhibition of HIV-reverse transcriptase activity by somephloroglucinol derivativesrdquo FEBS Letters vol 286 no 1-2 pp83ndash85 1991

[52] T Furumoto N Ozawa Y Inami et al ldquoMallotus philippinensisbark extracts promote preferential migration of mesenchymalstem cells and improve wound healing in micerdquo Phytomedicinevol 21 no 3 pp 247ndash253 2014

[53] Maeda ldquoMethod for producing Mallotus philippinensis dyecomposition and the compositionrdquo US7556829 B2 2009

[54] C Wiart Medicinal Plants of the Asia-Pacific Drugs for theFutureWorld Scientific Singapore 2006

[55] V R Sharma ldquoA review on endangered plant of Mallotusphilippinensis (Lam) MArgrdquo Pharmacologyonline vol 3 pp1256ndash1265 2011

[56] V Tangpu T Temjenmongla and A K Yadav ldquoAnticestodalproperty of Strobilanthes discolor an experimental study inHymenolepis diminutamdashratmodelrdquo Journal of Ethnopharmacol-ogy vol 105 no 3 pp 459ndash463 2006

[57] V Tangpu K Temjenmongla and A K Yadav ldquoAnticestodalactivity ofTrifolium repens extractrdquo Pharmaceutical Biology vol42 no 8 pp 656ndash658 2004

[58] A K Yadav and T Temjenmongla ldquoAnticestodal activity ofHouttuynia cordata leaf extract againstHymenolepis diminuta inexperimentally infected ratsrdquo Journal of Parasitic Diseases vol35 no 2 pp 190ndash194 2011

[59] T Temjenmongla and A K Yadav ldquoAnticestodal efficacy ofLasia spinosa extract against experimental Hymenolepis dimin-uta infections in ratsrdquo Pharmaceutical Biology vol 44 no 7 pp499ndash502 2006

BioMed Research International 13

[60] M L Dhar M M Dhar B N Dhawan B N Mehrotra and CRay ldquoScreening of Indian plants for biological activityrdquo IndianJournal of Experimental Biology vol 6 no 4 pp 232ndash247 1968

[61] Temjenmongla and A K Yadav ldquoAnticestodal efficacy offolklore medicinal plants of Naga tribes in north-east IndiardquoAfrican Journal of Traditional Complementary and AlternativeMedicines vol 2 pp 129ndash133 2005

[62] T V Tangpu and A K Yadav ldquoAnticestodal efficacy of Psidiumguajava against experimental Hymenolepis diminuta infectionin ratsrdquo Indian Journal of Pharmacology vol 38 no 1 pp 29ndash32 2006

[63] R Singh A Mehta P Mehta and K Shukla ldquoAnthelminticactivity of Rhizome extracts of Curcuma longa and Zingiberofficinalerdquo International Journal of Pharmacy and Pharmaceu-tical Sciences vol 3 no 2 pp 236ndash237 2011

[64] M K Asha D Prashanth B Murali R Padmaja and A AmitldquoAnthelmintic activity of essential oil of Ocimum sanctum andeugenolrdquo Fitoterapia vol 72 no 6 pp 669ndash670 2001

[65] J B Githiori J Hoglund P J Waller and R L Baker ldquoTheanthelmintic efficacy of the plantAlbizia anthelmintica againstthe nematode parasites Haemonchus contortus of sheep andHeligmosomoides polygyrus of micerdquo Veterinary Parasitologyvol 116 no 1 pp 23ndash34 2003

[66] N M Enwerema J I Okoguna C O Wambebea D A Oko-rieb and P A Akahc ldquoAnthelmintic activity of the stem barkextracts of Berlina grandiflora and one of its active principlesBetulinic acidrdquo Phytomedicine vol 8 pp 112ndash114 2001

[67] Z Iqbal M Lateef A Jabber M N Ghayur and A HGilani ldquoIn vitro and in vivo anthelmintic activity of Nicotianatabacum L leaves against gastrointestinal nematodes of sheeprdquoPhytotherapy Research vol 20 no 1 pp 46ndash48 2006

[68] Z Iqbal M Lateef A Jabbar G Muhammad and M N KhanldquoAnthelmintic activity of Calotropis procera (Ait) Ait F flowersin sheeprdquo Journal of Ethnopharmacology vol 102 no 2 pp 256ndash261 2005

Submit your manuscripts athttpwwwhindawicom

PainResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom

Volume 2014

ToxinsJournal of

VaccinesJournal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AntibioticsInternational Journal of

ToxicologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

StrokeResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Drug DeliveryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in Pharmacological Sciences

Tropical MedicineJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AddictionJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

Emergency Medicine InternationalHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Autoimmune Diseases

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Anesthesiology Research and Practice

ScientificaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Pharmaceutics

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Page 13: Mallotus philippinensis Muell. Arg (Euphorbiaceae ...

BioMed Research International 13

[60] M L Dhar M M Dhar B N Dhawan B N Mehrotra and CRay ldquoScreening of Indian plants for biological activityrdquo IndianJournal of Experimental Biology vol 6 no 4 pp 232ndash247 1968

[61] Temjenmongla and A K Yadav ldquoAnticestodal efficacy offolklore medicinal plants of Naga tribes in north-east IndiardquoAfrican Journal of Traditional Complementary and AlternativeMedicines vol 2 pp 129ndash133 2005

[62] T V Tangpu and A K Yadav ldquoAnticestodal efficacy of Psidiumguajava against experimental Hymenolepis diminuta infectionin ratsrdquo Indian Journal of Pharmacology vol 38 no 1 pp 29ndash32 2006

[63] R Singh A Mehta P Mehta and K Shukla ldquoAnthelminticactivity of Rhizome extracts of Curcuma longa and Zingiberofficinalerdquo International Journal of Pharmacy and Pharmaceu-tical Sciences vol 3 no 2 pp 236ndash237 2011

[64] M K Asha D Prashanth B Murali R Padmaja and A AmitldquoAnthelmintic activity of essential oil of Ocimum sanctum andeugenolrdquo Fitoterapia vol 72 no 6 pp 669ndash670 2001

[65] J B Githiori J Hoglund P J Waller and R L Baker ldquoTheanthelmintic efficacy of the plantAlbizia anthelmintica againstthe nematode parasites Haemonchus contortus of sheep andHeligmosomoides polygyrus of micerdquo Veterinary Parasitologyvol 116 no 1 pp 23ndash34 2003

[66] N M Enwerema J I Okoguna C O Wambebea D A Oko-rieb and P A Akahc ldquoAnthelmintic activity of the stem barkextracts of Berlina grandiflora and one of its active principlesBetulinic acidrdquo Phytomedicine vol 8 pp 112ndash114 2001

[67] Z Iqbal M Lateef A Jabber M N Ghayur and A HGilani ldquoIn vitro and in vivo anthelmintic activity of Nicotianatabacum L leaves against gastrointestinal nematodes of sheeprdquoPhytotherapy Research vol 20 no 1 pp 46ndash48 2006

[68] Z Iqbal M Lateef A Jabbar G Muhammad and M N KhanldquoAnthelmintic activity of Calotropis procera (Ait) Ait F flowersin sheeprdquo Journal of Ethnopharmacology vol 102 no 2 pp 256ndash261 2005

Submit your manuscripts athttpwwwhindawicom

PainResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom

Volume 2014

ToxinsJournal of

VaccinesJournal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AntibioticsInternational Journal of

ToxicologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

StrokeResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Drug DeliveryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in Pharmacological Sciences

Tropical MedicineJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AddictionJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

Emergency Medicine InternationalHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Autoimmune Diseases

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Anesthesiology Research and Practice

ScientificaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Pharmaceutics

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Page 14: Mallotus philippinensis Muell. Arg (Euphorbiaceae ...

Submit your manuscripts athttpwwwhindawicom

PainResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom

Volume 2014

ToxinsJournal of

VaccinesJournal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AntibioticsInternational Journal of

ToxicologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

StrokeResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Drug DeliveryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in Pharmacological Sciences

Tropical MedicineJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AddictionJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

Emergency Medicine InternationalHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Autoimmune Diseases

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Anesthesiology Research and Practice

ScientificaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Pharmaceutics

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of