12

2.1 INULA RACEMOSA HOOK. F (ASTERACEAE)

It is a stout herbaceous alpine perennial, 1.5 m tall, with very large basal

leaves and usually terminally borne, yellow flower heads (Fig 1).

2.1.1 TAXONOMICAL HIERARCHY

Kingdom: Plantae

Phyllum: Magnoliophyta

Class: Magnoliopsida

Order: Asterales

Family: Asteraceae

Tribe: Inulae

Genus: Inula

Species: Inula racemosa

2.1.2 SYNONYMN

Inula royleana (C.B.Clarke)

2.1.3 VERNACULAR NAMES

English: Inula, Indian elecampane, Sunspear

Sans & Hindi: Pushkar mool

Kashmiri : Poshkar, manurucha, mano

2.1.4 COMMERCIAL ADULTERANT/SUBSTITUTE

Saussurea lappa Clarke (Asteraceae)

2.1.5 DISTRIBUTION

The plant is distributed in temperate alpine Himalayas at an altitude of 1,500-

4,200 from Kashmir to Kumaon, Afghanistan to Central Nepal. It occurs wild among

13

strong alpine scrub vegetation in the cold arid habitat of NW Himalayas between

2,700-3,500 m in the eastern Ladakh (Leh) region of Kashmir.

Domesticated forms of this incipient cultigen is cultivated on borders of

agricultural fields of wheat, barley and buckwheat both in Kashmir and Lahaul valley

of Himachal Pradesh [1959]

Inula racemosa is a critically endangered species due to the fragile nature of

its habitat, and its exploitation due to commercial medicinal properties. The species is

facing the onslaught of indiscriminate over exploitation, habitat destruction and

competition. The populations of the species in the entire north western Himalayan

range are witnessing a speedy decline in density, dwindling both in size and number

[Parvaiz et al. 2006]

2.1.6 MORPHOLOGY

The plant is a stout shrub, bearing large leaves arranged in a racemose manner.

The stem is grooved and all vegetative parts are scabrid tomentose. Lower leaves are

narrowed to a winged leaf stack. Upper leaves are lanceolate and stem clasping. The

abaxial laminal face is densely tomentose. Radical leaves are 40 x 20 cm broad and

are elliptic lanceolate with long petioles. The cauline leaves are smaller, oblong and

semi aplexicaule. It also "dies very well" in the fall making a stately specimen with

shiny bronze foliage for winter interest.

The flowers are large, shady yellow daisies produced in mid to late summer.

They are borne on apical spike like cluster.

The fruits, slender achenes, 0.4 cm long, bearded with 0.75 cm long pappus

hairs. Root stock branched; fresh roots are irregularly fusiform (20-25 x 5 cm).

Sometimes a number of roots are found in the collar zone, though usually few occur

in each clump. These roots have a dull brownish skin with yellowish colour inside.

They possess a sweet and somewhat camphoraceous odour and have a bitter taste

[Chopra et al. 1956a].

14

Figure 1 - Inula racemosa habit roots

2.1.7 ETHNOMEDICAL USES

Pushkarmool commercially is a very important medicinal plant of the North

western Himalayas. The plant is used in Ayurveda as an expectorant and resolvent in

indurations. Considered a ‘Rasayana’(rejuvenator, immunomodulator) by Ayurvedic

physicians, the drug according to Bhavaprakasha [Bhavaprakasha 1961] is bitter

pungent in taste. When administered it mitigates vatakapha jwara (fever caused by

vata pitta imbalance), sotha (swelling), arachi (anorexia), swasa (breathlessness) and

parswasoola (pain in the sides of the chest).

The root is medicinal and considered a specific for cough, dyspnea, asthma,

pleurisy, tuberculosis and chest pain especially pre cordial pain. The aqueous extract

of the fresh or dry roots is given orally in rheumatic pains and liver problems.

Externally a paste or liniment is used for relieving pain. The root is also used in

15

veterinary medicine as a tonic [2002]. The root forms an important ingredient of

several polyherbal fomulations for heart diseases and inflammatory conditions of

spleen and liver [1978]. Along with Commiphora mukul, the drug combination called

‘pushkar guggulu’ is a popular anti obesity, hypolipidemic indicated in cardiac

ailments.

Inula racemosa is used in Chinese medicine for abdominal distension and

pain, acute enteritis and bacillary dysentery [Pharmacopoeia Committee of the

Ministry of Health 1995].

2.1.8 BIOLOGICAL ACTIVITIES REPORTED

Root powder is reportedly hypoglycemic and hypocholesterolemic in human

subjects [Tripathy et al. 1979]. It brought about a beneficial improvement in ST-T

changes in ECG of patients with Ischemic heart disease (IHD) [Tripathy et al. 1984].

At 450 mg/kg it enhanced PGE2 like activity in isoproterenol induced myocardial

ischemia in rabbits.

In combination with guggulu it is anti anginal and hypolipidemic in patients

with IHD [Ramji et al. 1991]. In multi herb combination with Terminalia arjuna and

Commiphora mukul, it is reported to exert cardioprotective effect in isoproterenol

induced myocardial ischemia in rats [Seth et al. 1998]. Inula racemosa with

Gymnema leaf extrract reduced corticosteroid induced hyperglycemia in mice

[Gholap and Kar 2003].

Petroleum ether extract at 200 µg has been reported to exhibit negative

chronotropic and positive ionotropic effect on isolated frog heart. At 400 mg/kg it is

reported to have shown adrenaline induced beta blocking activity in rats [Tripathi et

al. 1988].

The aqueous, methanolic and total aqueous extract showed better

hepatoprotective activity than the petroleum ether extract at 100 mg/kg in rats and

they were non toxic upto 10 g/kg. The LD50 of pet ether extract is reportedly 1.5g/kg

bw [Rao and Mishra 1997].

16

The alcoholic extract is non toxic upto 2100 ± 60 mg/kg i.p in rats and

provided significant protection against egg albumin induced passive cutaneous

anaphylaxis [Srivastava et al. 1999].

The crude alcoholic extract exhibited anti dermatophytic and anti cholinergic

activities, the former reportedly localized in the hexane soluble fraction [Tripathi et

al. 1978].

2.1.9 CONSTITUENTS ISOLATED

Chemical investigations of the genus Inula have shown that there are 2 main

groups of plants. One containing sesquiterpene lactones, especially eudesmanolides

and one containing simple thymol derivatives [Maxmuller H 1975].

Inula racemosa yields large amounts of sesquiterpene lactones, Alantolactone

(ALT) and isoalantolactone (IALT) [Arora et al. 1980]. Dihydroalantolactone,

dihydro isoalantolactone, inunolide [Raghavan et al. 1969], dihydroinunolide,

neoalantolactone, isoalloalantolactone [Ravindranath et al. 1978], alloalantolactone

[Prabha and Rastogi 1983], inunal, isoinunal [Kalsa et al. 1988], alantodiene and

isoalantodiene [Kalsa et al. 1989] are other sesquiterpene lactones isolated from the

non polar fractions of the root.

Daucosterol and Beta sitosterol have also been reported in quantity from the

roots [Tan et al. 1998].

1.3-2.6% essential oil is reported to be obtained from Inula racemosa from

Kashmir and it is constituted of ca 60% sesquiterpenes, although the most abundant

constituent is aplotaxene (hepta deca,1,8,11,14- tetraene ca 22%) apart from

phenylacetonitrile (ca 2%) [Bokadia et al. 1986].

Roots of ‘mano’ from Kashmir is reported to yield 5.7-6.2% petroleum ether

extract [Singh et al. 1959], while those from Lahaul valley, Himachal Pradesh

reportedly yield 8.5%w/w constituted of 83%lactones.The major lactones ALT and

IALT are in the ratio 4:6.

17

Investigation on the aerial parts of Inula royleana reported the presence of

several other sesquiterpene lactones namely ivalin acetate, 2d-OH alantolactone, 1-

desoxy-8-epi-ivangustin, 8-epi-isoivangustin, 9β-OH costunolide, 9 β-propionyl

oxycostunolide, 9 β-(2-methylbutaryloxyl) costunolide, 4β-5α-epoxy-10 α, 14H-

inuviscolide, 4β, 5α-epoxy-4,5-cis-inunolide, 4H-tomentosin, 4H carbrone [Ferdinand

et al. 1978].

2.1.10 BIOLOGICAL ACTIVITIES OF ISOLATED CONSTITUENTS

Sesquiterpene lactones have received considerable attention because of their

numerous biological activities [Picman 1986]. They are secondary plant metabolites

that play an important role in protecting plants against pathogenic organisms,

herbivorous insects or mammals. In addition, these compounds, exert their

allelopathic effects on other flora and vertebrate poisoning [Vidari et al. 1976].

Alantolactone and isoalantolactone [Milman 1990]

ALT and IALT are typical representatives of the sesquiterpene lactones found

in a number of plants of the family Compositae. A mixture containing both lactones

and called helenin (or Inula camphor) has long been known. In antiquity Elecampane

(Inula helenium), which contains ALT and IALT was added to food as a seasoning

and in the middle ages it began to be used for medical purposes. Today this mixture

serves as the active principle of the antiulcer drug Alanton. It is used in the treatment

of gastric ulcers and duodenal ulcers. The drug exhibits an anti inflammatory action,

decreases the proteolytic activity of the gastric juice and raises a lowered acid

formation function of the stomach without appreciably affecting a normal or raised

function. Alanton stimulates the formation of mucin and intensifies the regenerative

capacity of the gastric mucosa. Helenin possesses pronounced hemostatic action. The

results of experiments on animals with multiple injections have shown shortened

clotting time at 3 mg/kg by 75%. ALT and IALT are secondary metabolites and have

no obvious function in the basic metabolic processes and play an important role in

protecting plants from phytophagous pests. ALT and IALT are reportedly antifeedant

to granary pests [Streibl et al. 1983]

18

Effective as plant growth regulators at 15-20 mg/L ALT and IALT increased

number of rootlets of Phaseolus aureus by a factor of 2-2.5 as compared with control

experiment [Kaur and Kalsi 1985].

IALT is herbicidal on account of its lipophilicity as it gets incorporated into

cell membrane and does not pass into the other parts of the plant [Dalvi et al. 1971].

As early as the 1930’s the toxicity of lactones ALT and IALT has been studied

in mice. The minimum lethal dose for both compounds was 2000 mg/kg.

At doses of 100-200 mg/kg ALT and IALT increased the antioxidant activity

of lipids, their action considerably exceeding the activity of α-tocopherol and

ubiquinone.

It has been found in experiments in guinea pigs that helenin possesses an

antitussive activity, but this is only half that of codeine.

Inspite of the anti inflammatory action exhibited by helenin, IALT in a

concentration of 37 µM in an in vitro experiment did not inhibit the biosynthesis of

prostaglandins. It has been shown that ALT inhibits the microsomal enzymes of the

liver [Dalvi and Mcgowan 1982].

The antibacterial properties of ALT and IALT against a number of gram

positive and gram negative bacteria have been studied and ALT is completely

inhibitory to B.subtilis, while IALT exhibited weak activity in relation to B.subtilis

and B.vulgaris. At concentrations of 31.2-62.5 and 31.2 µg/ml respectively, ALT and

helenin possessed a pronounced inhibitory effect against pathogenic bacteria S.aureus

and Mycobacterium tuberculosis. The antifungal activity of ALT and IALT has been

studied in relation to more than 16 different cultures and both lactones inhibited the

growth of all the fungi studied, but the effects for each individual culture differed

greatly. Both ALT and IALT exhibited their greatest inhibitory effect on the growth

of the zoophilic fungi Microsporium cookie and Trichophyton mentagrophytes.

Studies on SAR of several sesquiterpenes with respect to antibacterial and

antifungal activities revealed multivalent reasons for their activity, inexplicable for

19

eg., by the presence or absence of an α- methylene group in the lactone ring alone

[Picman 1984].

The antiprotozoal properties of ALT and IALT in relation to the dysentery

amoeba Entamoeba histolytica and a number of strains of Trichomonas vaginalis 46

have also been studied in vitro. Out of the 82 sesquiterpene lactones investigated,

ALT and IALT were among the ten most active compounds.

Lactones ALT and IALT possess anthelmintic activity. The action of 12

nitrogen containing derivatives of ALT and IALT has been studied in relation to

Hirudo medicinalis (leech) Lumbricus terrestris (earthworm) and Ascaris suum

(helminth). The most active were the products of the addition of pyrrolidine to IALT

and of 4-methyl piperidone to ALT.

Analysis of the activity of a number of sesquiterpene lactones in relation to the

nematode Meliodogyne incognito has shown that the activity exhibited is connected to

the presence of α- methylene-γ- lactone group in the molecule. The result of the action

of the lactone ALT on nematodes was 97% mortality.

It is known that compounds possessing anthelmintic activity frequently also

exhibit anticarcinogenic activity. An investigation of the cytotoxic properties of

helenin in comparison with the individual lactones ALT and IALT showed that the

activity of helenin is connected with the presence of IALT in it [Ohta et al. 1977]. The

model used was a culture of human epidermal carcinoma cells. The cytotoxicities of

ALT and IALT have also been determined in in vitro experiments on lines of human

lung carcinoma cells [Wordenbag et al. 1986]. LD50 for ALT was 4.6 µg/ml: and for

IALT, 16 µg/ml. A dose of 50µg/ml completely suppressed the growth of cells.

Presence of the reactive group –CH=C-C=O is one of the main conditions for

the biological activity of sesquiterpene lactones, and in particular, ALT and IALT.

The mechanism of their cytotoxic effect is also treated as a Michael addition reaction

between this grouping and the SH groups of enzymes and proteins [Kupchan et al.

1971]. The role of lipophilicity in the biological activity of the sesquiterpene lactones

has been demonstrated. For example, for IALT, ivalin (2-OH alantolactone) and

20

ivasperin (1,2-dihydroxyalantolactone), cytotoxicity increases with an increase in

lipophilicity [Abeysekara et al. 1985].

Many natural sesquiterpene lactones containing an α- methylene-γ- lactone

grouping cause allergic contact dermatitis. The importance of the reactivity of the

lactone grouping has been shown in model experiments using as examples the

interaction of ALT with a number of amino acids (cysteine, tryptophan, histidine,

lysine), as a result of which ALT lost its immunological reactivity [Dupuis et al.

1974]. At the same time there is information on the toxicity of both ALT and 11,13

dihydro alantolactone in relation to a culture of leukocytes in vitro [Dupuis and

Brisson 1976]. The authors concerned put forward a hypothesis that the toxicity of

ALT is not connected with α- methylene-γ- lactone grouping.

Thus the broad spectrum of the biological activities of alantolactone and

isoalantolactone completely justifies the Russian name of the compound from which

these compounds were isolated – devyasil (nine powers).

Alantolactone and isoalanto lactone, thus remain the object of active

investigation both in relation to chemical properties and in relation to biological

activity [Milman 1990].

Other Lactones

Alantodiene and isoalantodiene isolated from Inula racemosa have displayed

biological activity as plant growth regulators, which not only initiate adventitious root

formation in the stem cuttings of Vignata radiate, but also increase the nitrate

reductase activity in the plant [Kalsa et al. 1988]. Isoinunal isolated from Inula

racemosa displays considerable root initiation activity with hypocotyl cuttings of

Phaseolus aureus [Prabha and Rastogi 1983]. Isoinunal and isoalloalantolactone

were found to cause adventitious root formation on stem cuttings of Phaseolus

aureus.

21

2.1.11 JUSTIFICATION FOR INCLUSION IN THE STUDY

Inula racemosa (IR) has been selected for inclusion in this study on the

following grounds:

• Root is a reputed traditional drug indicated for precordial chest pain by

Susruta the legendary physician/compiler of the ‘Susruta samhita’ a classic

treatise on Ayurvedic medical practice

• Clinical trials of the root powder indicated its hypolipidaemic activity apart

from effecting beneficial ST-T segment changes in ECG of IHD patients

• Alcoholic extract of the root is reportedly cardioprotective in isoproterenol

induced myocardial ischaemia in rabbits

• Petroleum ether extract of the root has exhibited a negative chronotropic and

positive ionotropic effect on isolated frog heart and has shown adrenaline

induced beta blocking activity in rats

• The roots are rich in sesquiterpene lactones known for their powerful

biological activity and generic inhibition of enzymes

• Alantolactone and isoalantolactone, the major constituents are attributed with

a rich spectrum of bio activity

• Anti inflammatory activity of lactones is extensively reported

• The antioxidant activity of the lactones has also been reported

• the root has never been studied for anti atherosclerotic activity

• Demonstration of such an activity shall give scientific validation to traditional

medicine claims and pave way for exploration of mechanism of action of the

extracts and/or phytoisolates

22

2.2 LITERATURE ON ERYTHRINA VARIEGATA LINN.

(LEGUMINOSAE)

A medium sized, quick growing tree reaching a height up to 60 ft, belonging

to the family Leguminosae, Subfamily, Papilionaceae [Gamble 1935; Henry et al.

1987]. It is cultivated in gardens as an ornamental. A number of horticultural forms

are recognized, among them the well known ones are forma alba with white flowers

and forma parcelli with variegated leaves and bright orange to deep red coloured

flowers [1952].

2.2.1 TAXONOMICAL HIERARCHY

Kingdom: Plantae

Division: Magnoliophyta

Class: Magnoliopsida

Order: Fabales

Family: Fabaceae

Subfamily: Faboidae

Tribe: Phaseoleae

Genus: Erythrina

Species: variegata

2.2.2 SYNONYMN

Erythrina indica

2.2.3 VERNACULAR NAMES

English: Tiger’s claw, Sunshine tree, Indian coral tree

Sans: Mandar, parijata

Hin: Dadap

Tel: Badisa, modugu

Tam: Kalyana murungai, Kalyana murukku

23

2.2.4 OTHER RELATED SPECIES

E.suberosa, E.fusca Lour, E.blakei, Hort, E.caffra, E.corallodendron Linn,

E.humeana. Spreng Syn E .humei, E.tomentosa

2.2.5 DISTRIBUTION

The genus Erythrina is distributed in the tropical and subtropical regions of

the world and encompasses over 100 species. Erythrina variegata is native to tropical

and subtropical regions of eastern Africa, southern Asia, northern Australia and the

islands of the Indian ocean and the western Pacific ocean east to Fiji. The tree is

found wild in deciduous forests throughout India especially the upper gangetic plains

of India and Nepal [Sarragiotto et al. 1981]. About 8 indigenous species and 10

introduced ones occur in India. Many of the species of Erythrina are cultivated in

India for their showy flowers; they are also grown in plantations as shade trees and for

green manure.

2.2.6 GENERAL MORPHOLOGY

Erythrina is a genus of trees or shrubs, rarely herbs and usually armed with

spines. Erythrina variegata is a medium sized, quick growing tree reaching a height

up to 27 m (Fig 2). Tree bears coarse spines on trunk and branches, bark is smooth,

yellowish or greenish grey, shining, peeling off in thin papery flakes; branchlets

armed with small dark colored conical prickles upto 3rd or 4th year [Huxley 1992].

Leaves are variegated along major veins or not, trifoliate, variable in size with

leaflet blades broadly triangular and upto 30 cm long. Leaflets are 4-6 in long and

nearly as broad. Flowers appear in Jan- Mar and fruits ripen in May-July. Flowers

large, white or bright orange to deep red, pea flower like, are borne in dense racemes

upto 6-12 in long containing upto 12 seeds. Fruit a pod with large red seeds which are

oblong, smooth, red to dark purple or brown [1952].

2.2.7 ETHNOMEDICAL USES

The leaves and tender shoots of the plant are eaten as pot-herb [Whistler and Elevitch

2006]. This plant has folkloric reputation for medicinal properties in India, China and

24

Indochina [Chopra et al. 1956b]. Different parts of the plant have been used in

traditional medicine as a nervine sedative, collyrium in opthalmia, anti asthmatic, anti

epileptic, antiseptic and as an astringent [Mitscher et al. 1987].

Figure 2. Indian Coral tree - habit

The bark is used as febrifuge, antiseptic and for treatment of liver disorders.

The leaves are reputedly stomachic, diuretic and able to provide pain relief in joints.

In the islands of the South Pacific, it is used in the treatment of filariasis, as a remedy

25

for swollen armpits, swollen breasts, stomachache and coughs. In new guinea, an

infusion of the root is used to treat bronchitis [1998].

Erythrina variegata is also used in folk medicine in southern parts of Japan

and China as an anti bacterial, anti pyretic and as a collyrium. These properties are

used in Chinese herbal medicine for the treatment of pyrexia, scabies and septicemia

{College, 1977). The plant is used in Samoa in the treatment of inflammation and

inflammation like processes [Weiner 1984]. The plant is specifically valued for its

curare like action [Ghosal et al. 1972].

In India the leaves are used as a poultice to reduce fevers and is indicated as an

antiobesity drug in Siddha system of medicine [Yoganarasimhan 2000].

2.2.8 BIOLOGICAL ACTIVITIES REPORTED

Different parts of the plant are reported with insecticidal, haemagglutinating

activity, curaric, skeletal muscle relaxant, feeding deterrent, anti spasmodic and anti

mycobacterial activity [Telikepalli et al. 1990a]. Leaf extract is reported to possess

nematocidal property and is highly toxic to Meliodogyne incognita and

Tylenchorchynchus mashoodi at 1:1 and 1:5 concentrations [Rajareddy and

Sudarshanam 1987].

Root extracts possess anti microbial activity in vitro against Staphylococcus

aureus and Mycobacterium smegmatis [Telikepalli et al. 1990a]. Alcoholic extract of

stem bark of Erythrina variegata at 300-600 mg/kg for 14 weeks prevented

ovariectomy induced increase in serum osteocalcin, alkaline phosphatase and urinary

free deoxy pyridinoline levels. The extract also is reported to prevent

histomorphometrically demonstrable estrogen deficiency and a decrease in trabecular

thickness and area as observed in the tibial proxima [Zhang et al. 2007]. The extract

also improved the energy absorption and stiffness of the midshaft of the rat femur,

indicating ability of the plant extract to suppress the high rate of bone turnover

induced by estrogen deficiency, inhibit bone loss and improve the biomechanical

property of bone in ovariectomized rats. Extracts of various species of Erythrina

exhibit curare like action which is attributable to the presence of hypaphorine [Marion

1960].

26

2.2.9 CONSTITUENTS ISOLATED

The plant is a rich source of alkaloids and they have been isolated from 50

species of the 105 known species of Erythrina [Marion 1960]. Alkaloids of

tetracyclic erythrina type inclusive of tetrahydro isoquinoline type - Erythraline,

erythratine, erythroidine, erysodine, erysotrine, erysotine, epierythritidine, 11- OH

epierythritidine, 11-OH erysotrine, erythronine and hypaphorine are alkaloids isolated

from the root and bark.

The plant is a prolific source of isoflavones, pterocarpans and biphenyls.

Isoflavones erythrinins A,B and C, osajin and alpinum isoflavone in addition to the

styrene oxyresveratrol and dihydro stilbene, dihydroxy resveratrol apart from linear

pyrano isoflavones, robustone and 4-O- methyl alpinum isoflavone are isolated from

the bark [Deshpande et al. 1977; Masouda et al. 1991].

Flowers contain erythritol, 7-methoxy 8-(15-OH pentadecyl)-coumarin,

abyssinone, stigmoidins A,B and C, alpinum isoflavone, erythrinin A,B and C, osajin,

erythrabasin I, phaseollin,besides isoquinoline and isococcoline alkaloids, apart from

29-norcycloartenol, 3-β-acetoxy- β-norcholest-5-ene, docosanoic and capric acid

[Sharma and Chawla 1992].

Seeds are rich in protein like chick-pea. They also contain isolectins (EVLI,

EVLII and EVL III), kuntz-type trypsin inhibitors ETIa and ETIb and chymotrypsin

inhibitor ECI [Dutta and Basu 1981]. Warangalone, Eryvarins F and G, [Tanaka et al.

2003] 5,7,4’-trihydroxy-6-8-diprenyl isoflavone, erycristagallin, erythrabyssin-II,

phaseolin, phaseolidin, isobavachin, cinnamyl phenol, eryvaristyrene [Telikepalli et

al. 1990b], diphenyl propan-1,2-diols, eryvarinols A and B [Tanaka et al. 2002] are

the constituents isolated from the roots. Leaves are reported to have a total alkaloidal

content of 0.11% constituting alkaloids erysovine, erysodine, erysotrine, erythrinine,

and orientaline [Ghosal et al. 1972; Ghosal et al. 1970].

2.2.10. BIOLOGICAL ACTIVITIES OF CONSTITUENTS ISOLATED

Total alkaloids isolated form the bark showed a muscle relaxant activity and

increased the sedative effects of hexabarbitol. The LD50 in mice is 30.4mg/kg. Seeds

27

are a source of potential biopesticides. Lectins from the seeds are D-galactose binding

and have haemagglutinating and leucoagglutinating property [Dutta and Basu 1981].

Some isoflavonoids exhibit anti bacterial , anti inflammatory activity [Telikepalli et

al. 1990a]. Flavonoids abyssinone V, erycristagallin and 4’-hydroxy-6,3’,5’-triprenyl

flavonone have phospholiase A2 inhibitory activity [Hegde et al. 1977]. Isoflavones

erythrinin B and euchrenone b10 inhibit the Na+/H+exchange system [Kobayashi et al.

1997].

2.2.11 JUSTIFICATION FOR INCLUSION IN THE STUDY

• Erythrina variegata (EV) has folkloric/traditional medicine reputation for anti

inflammatory activity in several Asian countries

• The plant is a rich source of alkaloids, some of which are of the tetrahydro

isoquinoline group reported with estrogen agonist/antagonist effect [Lin et al.

2007]

• Cardioprotective effects of estrogen is well established and it is known that the

direct effects of estrogen on the vasculature promote vasodilatation and inhibit

the development and progression of atherosclerosis [Farhat et al. 1996].

• Ev like soyabean belongs to Leguminosae and is rich in isoflavonoids reported

with a rich spectrum of biological activities like anti estrogenic, anti

inflammatory, cardioprotective, anti oxidant and anti thrombotic activities

• Epidemiological reports have associated soy products with reduced incidence

of breast and prostate cancer, cardiovascular disease, osteoporosis and lower

cholesterol [Clarkson et al. 1995].

• Isoflavones being structurally similar to mammalian estradiol [Setchell and

Adler 1988] are referred to as ‘phytoestrogens’. These are weakly estrogenic

and in model systems, are shown be anti estrogens, competing for oestradiol

at the receptor complex, yet they fail to stimulate a full estrogenic response

after binding the nucleus [Tang and Adams 1980]. This raises the possibility

that they may be protective in hormone related diseases such as breast cancer

[Setchell et al. 1984].

28

• Pharmacologically potent stryrene- resveratrol and dihydro stilbene di hydroxy

resveratrol are reported in addition to a rich spectrum of isoflavonoids from

the plant

• Some of the flavonoids isolated from the bark exhibited phospholipase A2

(PLA2) inhibitory activity. PLA2 is an important enzyme in phospholipid

catabolism, believed to be involved in a series of vital regulatory processes

through its ability to release arachidonic acid for the subsequent biosynthesis

of eicasanoids, implicated in the pathology of many diseases especially, those

involving inflammation and allergy. Newer research indicates atherosclerosis

to be an inflammatory disease. The ethnomedical usage of the plant as an anti

inflammatory and the reported activity are the prime reasons for the inclusion

of the plant in the study

• Root, bark, seeds and flowers have been investigated, but apart from alkaloids

isolated, little or no work is reported for leaves which are indicated in Siddha

medicine for anti obesity effect

On the above cited grounds, leaves of EV are selected for evaluation of anti

atherosclerotic potential

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2. (1998) Medicinal Plants in the South Pacific. WHO Regional Publications,

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3. (2002) Wealth of India-Raw Materials, First Suppl Ser,Vol lIII. NISCAIR-

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4. (1978) The Ayurvedic Formulary of India Part 1. Govt of India, Ministry of

Health and Family planning, Dept of Health, pp 7,8.

29

5. (1952) Wealth of India-Raw Materials, Vol. 3. CSIR-NISCAIR, New Delhi,

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6. Abeysekara BF, Abramowski Z, Towers GHN (1985) Chromosomal

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