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S60
Document heading doi: 10.1016/S1995-7645(14)60204-2
A review of therapeutic potential of Saussurea lappa-An endangeredplant from HimalayaKulsoom Zahara, Shaista Tabassum, Sidra Sabir , Muhammad Arshad, Rahmatullah Qureshi, Muhammad Shoaib Amjad,
Sunbal Khalil Chaudhari*
Department of Botany, PMAS Arid Agriculture University Rawalpindi, Pakistan
Asian Pac J Trop Med 2014; 7(Suppl 1): S60-S69
Asian Pacific Journal of Tropical Medicine
journal homepage:www.elsevier.com/locate/apjtm
*Corresponding author: Sunbal Khalil Chaudhari, Department of Botany, PMAS Arid
Agriculture University Rawalpindi, Pakistan.
E-mail: [email protected]
1. Introduction
1.1. Geographical distribution
Saussurea lappa (S. lappa ) is indigenous to
I nd ia , Pak i s t an and China , where i t g rows in
the Himalaya region at 2 500-3 500 m altitude [1 ].
1.2. Morphological description of S. lappa (Decne.) C.B.
Clarke plant
S. lappa C.B. Clarke, syn. Saussurea costus (Falc.) Lipsch
belonging to family Asteraceae (Table 1), commonly known
as Costus which is a tall, perennial herb that grows to a
height of 1-2 m; stem is upright, stout and fibrous while rootis a long stout of approximately 60 cm with a characteristic
odour; leaves are lobate, stalked, membranous, irregularly
toothed; upper leaves are small while basal leaves are large
with long lobately winged stalks. Flowers are stalkless, dark
purple to black in colour and are arranged in terminal and
axillary heads (Figure 1). Pappas is approximately 1.7 cm
long, fluffy, feathery giving an inquisitive appearance to the
fruiting flower heads. Fruit of S. lappa is cupped, curved,compressed and hairy[2].
2. Active constituents of S. lappa
Studies on the chemical ingredients of S. lappa could be
traced back to 1950s. Until now, many compounds have beenisolated. Its active constituents are mainly terpenes, but
it also contains anthraquinones, alkaloids and favonoids.
Plant has various terpenes that mainly have antitumor
properties and anti-infammatory, such as costunolide,
dihydrocostunolide, 12-methoxydihydrocostunolide,
dihydrocostus lactone, dehydrocostus lactone [3 ],α-hydroxydehydrocostus lactone, β-hydroxydehydrocostuslactone, lappadilactone[4], mokko lactone, betulinic acid,
betulinic acid methyl ester [5], cynaropicrin, reynosin,
santamarine[6], saussureamines A-C[7], α-cyclocostunolide,
alantolactone, isoalantolactone[8], isodihydrocostunolide,β-cyclocostunolide[9 ], 1β-hydroxy arbusculin A[5 ],
ARTICLE INFO ABSTRACT
There are 300 known Saussurea species. Among them, Saussurea lappa (S. lappa) is a
representative perennial herb, globally distributed across Himalaya region. S. lappa has beentraditionally used in medicines without obvious adverse effects. Despite significant progress inphytochemical and biological analyses of S. lappa over the past few years, inclusive and criticalreviews of this plant are anachronistic or quite limited in scope. The present review aims tosummarize up-to-date information on the active constituents, pharmacology, traditional uses,trade and challenges in conservation and sustainable use of S. lappa from the literature. Inaddition to botanical studies and records of the traditional use of S. lappa in over 43 diseases,scientific studies investigating the latent medicinal uses of this species and its constituentphytochemicals for a range of disorders are presented and discussed. The structure, bioactivity,and likely mechanisms of action of S. lappa and its phytochemicals are highlighted. Althoughsome progress has been made, further scrupulous efforts are required to investigate the individualcompounds isolated from S. lappa to validate and understand its traditional uses and developclinical applications. The present review offers preliminary information and gives direction forfurther basic and clinical research into this plant.
Article history:Received 30 Jun 2014
Received in revised form 23 Jul 2014
Accepted 10 Aug 2014
Available online 17 Sep 2014
Keywords:
Saussurea lappaHimalayaPhytochemicalsBioactivitiesClinical research
Contents lists available at ScienceDirect
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arbusculin B[10], saussureal and so on[11].
Table 1
Taxonomic Hierarchy of S. lappa C.B. Clarke.
Kingdom Plantae
Subkingdom Viridaeplantae
Infrakingdom Streptophyta
Division Tracheophyta
Subdivision SpermatophytinaInfradivision Angiospermae
Class Magnoliopsida
Superorder Asteranae
Order Asterales
Family Asteraceae
Genus Saussurea DC.
Species S. lappa C.B. Clarke
Figure 1. S. lappa floral part.
S. lappa has three anthraquinone compounds, namely,aloeemodin-8-O-β-d-glucopyranoside, rhein-8-O-β-d- glucopyranoside, and chrysophanol. Four favonoidglycosides have antibacterial function[12]. Shikokiols have
antitumor activity[13], whereas chlorogenic acid preventsoxidization.
3. Costus oil
The oil extracted from the roots of S. lappa is known ascostus oil, which is used in the preparation of hair oil and inhigh quality perfumes. Costus oil is pale yellow to brownishin color and is also said to be valuable in treating leprosy.
In a recent study, 39 components have been identifiedfrom the essential oil of S. lappa roots. The chief compoundswere dehydrocostus lactone (46.75%), costunolide (9.26%), 8-
cedren-13-ol (5.06%) and α-curcumene (4.33%). However,β-costol (13.55%) and δ-elemene (12.69%), α-selinene (5.02%),β-selinene (4.47%), α-costol (4.02%), 4-terpinol (3.38%),elemol (3.21%), α-ionone (3.13%), β-elemene (3.00%), (-)- γ-elemene (2.08%), p-cymene (1.96%) and 2-β-pinene (1.57%),(-)-α-selinene, (+)-selina-4, 11-diene, (-)-α-trans-bergamotene, (-)-α-costol, (+)- γ-costol, (-)-elema-1,3,11 (13)-trien-12-ol, (-)-α-costal, (+)- γ-costal, (-)-elema-1,3,11(13)-trien-12-al, (-)-(E)-trans-bergamota-2,12-dien-14-al, (-)-ar-curcumene, (-)-caryophyllene oxide and 12-methoxydihydrodehydrocostuslactone were also reported[14,15]. However, in the other reported studies, the proportionof all these compounds greatly differs. Existing variationsin the composition of S. lappa essential oil may be due tovarious factors related to ecotype, phenophases, chemotypeand variations in environment conditions such as relativehumidity, temperature, photoperiod and irradiance.Furthermore, the chemistry of secondary metabolites ofplants may also be affected by genetic background[16].
4. Pharmacology
S. lappa is a medicinally important plant. Variousactive compounds isolated from plant are reported tohave medicinal properties e.g. the major componentsare sesquiterpene lactones such as costunolide anddehydrocostus lactone. S. lappa possesses variousbioactivities such as antifungal [17], antidiabetic [18],anthelmintic[19], antitumor [20], antiulcer [21], antimicrobial[22],i m m u n o s t i m u l a n t[ 2 3 ], an t i i n f l ammato ry [ 2 4 ] andantihepatotoxic[25].
4.1. Anticancer/antitumor
Costunolide (isolated from root of S. lappa) was studiedfor its effect and supposed pathways of action on theinduction of apoptosis in HL-60 human leukemia cells.Using apoptosis analysis, evaluation of mitochondrialmembrane potentials and measurement of reactive oxygenspecies (ROS), it was proved that costunolide was a potentapoptosis inducer, and by ROS generation aiding its activity,it induced mitochondrial permeability transition andreleased cytochrome C to the cytosol. In cells treated withcostunolide, an antioxidant N-acetylcystein is responsiblefor blocking the mitochondrial alteration, ROS production,
and consequent apoptotic cell death. Costunolide stimulatesthe ROS-mediated mitochondrial permeability transition andresultant cytochromes C release[26]. The hexane extract of S. lappa was investigated for thechemo preventive potential in autonomous androgen prostatecancer and apoptosis induction in DU145 cells. Results ofthis study showed that dehydrocostus lactone isolated fromthe hexane extract of S. lappa induced apoptosis in cell linesof DU145 human autonomous androgen prostate cancer andinhibited the cell growth[27]. Cynaropicrin isolated from S. lappa was assessedfor its immunomodulatory effects on cytokine release,immunosuppressive effects, and nitric oxide production.
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Cynaropicrin repressed Jurkat T, Eol-1 and U937 celllines in a dose-dependent manner with IC50 values of 2.36,10.90 and 3.11 µmol/L respectively. Further, by means ofDNA disintegration, cell cycle arrest and morphologicalanalysis via U937 cells, its cytotoxic effect is studied. Whencynaropicrin is treated in combination with ROS scavengers’ rottlerin, N-acetyl-L-cysteine or L-cysteine repressed thecynaropicrin mediated cytotoxicity. The results showed that
cynaropicrin was more cytotoxic toward leukocyte derivedcancer cells than fibroblasts[28]. Costunolide is a sesquiterpene lactone isolated from S.lappa proved to have effect on carcinogenesis via reportergene assay, persuaded by a tumor endorsing phorbol ester12-O-tetradecanoylphorbol-13-acetate at cellular level.The activity of nitric oxide synthase is amplified by tumorpromoting phorbol ester 12-O-tetradecanoylphorbol-13-acetate which consecutively repressed by costunolide withthe IC50 value of 2 mmol/L[29].
In another study, the effect of costunolide on telomeraseinhibitory activity was investigated on MDA-MB-231,MCF-7 cells which confirmed the hindering activity[30].
Dehydrocostuslactone is another sesquiterpene lactoneisolated from S. lappa and investigated for anticancerpotential for non lung cancer cell lines, for exampleA549, NCI-H460 and NCI-H520 and its activity have beenconfirmed[31]. Ethanolic extract of S. lappa showed that apoptosisfollowed in a dose and time dependent manner such as 80 µg/mL and 48 h which gives confirmation for the treatmentof gastric cancer by S. lappa[20]. Hepatocellular carcinoma activity of dehydrocostuslactonewas evaluated by in vitro assays, such as cell proliferationassay, immunoblot assay, assay for kinase activity,apoptosis and caspase activity assay. By using transmission
electron microscopy, the in vivo analysis was done. Theresults proved its anticancer activity at the IC50 values 16.7 and 18.8 µmol/L[32]. Costunolide and dehydrocostus lactone had beenisolated from different extracts of S. lappa. Costunolideand dehydrocostus lactone confirmed the cytolytic activityat ID 50 of 3.6-10 µmol/L. At 13 .6 µmol/L, costunolidecompletely inhibited the granule exocytosis in a dose-dependent manner and even repressed the amplificationin the tyrosine phosphorylation at different concentrations.Therefore, results disclosed that the costunolide performedin a mechanistic means by preventing the increase in thephosphorylation of tyrosine[33].
Costunolide inhibits the vascular endothelial growthfactor (VEGF)-induced chemotaxis of human umbilical veinendothelial cells in a dose-dependent manner. It was alsofound to selectively inhibit the endothelial cell proliferationinduced by VEGF. The result of this study showed thatby blocking the angiogenic factor signaling pathway,costunolide might inhibit angiogenesis. VEGF interactswith its cognate receptors, KDR /Flk-1 and Flt-1, and exertsits angiogenic effect. Costunolide is found to inhibit theautophosphorylation of KDR /Flk-1 without affecting thatof Flt-1. These results suggest that costunolide may proveto be useful for the development of a new angiogenesisinhibitor [34]. C-17 polyene alcohol isolated from S. lappa
exhibited moderate cytotoxicities against the human tumorcell lines A549, SK-MEL-2, SK-OV3, HCT 15 and XF 498[13].
4.2. Anti-inflammatory activity
In Korean traditional prescriptions, S. lappa is frequentlyused for inflammatory diseases. Methanol extract of S.lappa was investigated. It was observed that at 0.1 mg/
mL concentration, it exhibited more than 50% of inhibitionon the cytokine induced neutrophil chemotactic factorinduction[35]. Ethanolic extract of S. lappa was studied at a dose rangeof 50-200 mg/kg, for the acute and chronic inflammationinduced in both mice and rats. The result of this studyrevealed that the extract showed considerable values foranti-inflammatory activity through carrageenan inducedpaw edema and peritonitis animal models[36]. Costunolidewas investigated for anti-inflammatory activity and itwas observed that costunolide hindered the protein andmRNA expression of interleukin-1b. By means of anelectrophoretic mobility shift assay, it was confirmed that
it also concealed the AP-1 transcription activity. So, allthese activities proved the anti-inflammatory activity ofcostunolide[37]. The potential of dehydrocostus lactone for the oxidativeosteoblast damage was investigated and showedconsiderable increase in the osteoblast growth andhydrogen peroxide. At 0.4-2 µg/mL of dose, the factorsfor example calcium deposition, collagen and alkalinephosphatase were improved. These results confirmed thatdehydrocostus lactone compound had potential to be usedagainst oxidative osteoblast damage[5]. At the doses of 50, 100 and 200 mg/kg, the ethanolicextracts of S. lappa were assessed for their action on acute
and chronic inflammation and at 50-200 mg/kg it showedconsiderable inhibition on carrageenan induced pawedema[36].
4.3. Hepatoprotective
Constunolide and dehydrocostus lactone (isolated from S.lappa) had little effect on the viability of the cells. However,they showed inhibitory effect on human hepatoma Hep3B cells, and on the expression of the hepatitis B surfaceantigen (HBsAg). It is proved that these compounds inhibitthe HBsAg production by Hep3B cells with IC50 of 1.0 and 2.0 µmol/L, respectively. Northern blotting analysis proved that
they suppress (HBsAg) gene expression mainly at the mRNA level. Moreover, in another human hepatoma cell line HepA2 (derived from Hep G2 cells) by transfecting a tandemlyrepeat hepatitis B virus (HBV) DNA, the inhibitory effect ofcostunolide on replication of human liver cells was studied.Results showed that both costunolide and dehydrocostuslactone had the tendency to be developed as potent antiHBV drugs in the future[38].
4.4. Anti-ulcer and cholagogic
The acetone extract of S. lappa and costunolide showedcholagogic effect and inhibitory effect on the formation of
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gastric ulcer in mice[39]. The serum gastrin, variation ingastric acidity output, and plasma somatostatin concentrationwere observed during S. lappa decoction perfusion intothe stomach of patients with chronic superficial gastritisand results revealed that the decoction could increasethe endogenous motilin release and accelerate the gastricemptying[38]. S. lappa is one of the major ingredients of UL-409, a formulation which possesses anti-ulcer activity and
the activity is may be due to the intonation of defensivefactors by improvement in gastric cytoprotection[40,41]. Antiulcer activity of herbal formulation of S. lappa wastested in Wistar rats and male pigs. Orally 600 mg/kg drugwas given. The drug showed significant effect in gastriculceration induced by alcohol and aspirin, cold resistantinduced ulcerations and duodenal ulcer models. It amplifiedthe mucus discharge in all so it was proved to be anantiulcer agent[40].
4.5. Imunomodulator
Costunolide and dehydrocostus lactone act as inhibitors
of killing activity of cytotoxic T lymphocytes (CTL). Throughpreventing the increase in tyrosine phosphorylation,constunolide inhibited the killing activity of CTL in responseto the crosslinking of T cell receptors as inhibitors of thekilling function of CTL and the induction of intercellularadhesion molecule-1, dehydrocostus lactone from S.lappa and other guaianolides were examined for theirstructure activity relationship[33]. It was confirmed that theguaianolides moiety exhibited considerable inhibitory effectstowards the induction of intercellular adhesion molecule-1 and killing function of CTL[42].
4.6. Anticonvulsant activity
Different extracts of S. lappa root were evaluated for theanticonvulsant activity by picrotoxin-induced convulsions,pentylenetetrazole and maximal electroshock testsperformed in mice. It was proved that the petroleum extractof S. lappa roots showed potent anticonvulsant activity at adose of 100 and 300 mg/kg[43].
4.7. Gastric function
Decoction of S. lappa was given to patients affected withpersistent superficial gastritis and checked for differencein factors such as serum gastrin, gastric acidity and plasma
somatostatin. Decoction of S. lappa was also given to fivehealthy volunteers. It was observed that it sped up thegastric emptying time and discharge of endogenous motilin.However, no change is observed in plasma somatostatin,acidity output and serum gastrin levels[38].
4.8. Gastro-protective effect
Costunolide, saussureamines and dehydrocostus lactoneisolated from the methanolic extract of S. lappa showed thegastro-protective effect in rats on acidified ethanol inducedgastric mucosal lesions in a dose dependent manner (5 and10 mg/kg)[44].
4.9. Angiogenesis effect
Endothelial cell proliferation (induced by vascularendothelia growth factor ) is reported to be repressed bycostunolide (isolated from S. lappa root). Studies provedthat the chemotaxis induced by vascular endotheliagrowth factor of human umbilical vein endothelial cellswas noticeably inhibited at IC50 of 3.4 µmol/L. Similarly by
in vivo method the neo-vascularisation of mouse cornealstimulated by vascular endothelia growth factor is repotedto be inhibited at a dosage of 100 mg/kg/day. Inhibition ofvascular endothelia growth factor on VEGFR KDR /Flk-1 wasalso proved through signaling pathway[34].
4.10. Hypoglycaemic
When a comprehensive examination and clinical study onpotent hypoglycemic plants of different regions from Indiawas undertaken, S. lappa was found effective for obesediabetes[18].
4.11. Spasmolytic activity
From studies, it was proved that S. lappa was significantlyable to relax the contraction induced by carbachol (30 µmol/L). S. lappa has been reported to have antiperoxidativeeffects possibly due to the presence of sesquiterpenelactones. It is known to suppress contractions in guniea-pigaorta. Sesquiterpenes are recognized to stimulate the sGC which stimulates extrusion of K
+ ions and thereby reducesintrinsic Ca++ ions through activation of cGMP and PKG pathway, leading to relaxation of smooth muscles[32].
4.12. Anti-hepatotoxic activity
Aqueous and methanolic extracts of S. lappa root wereinvestigated for hepatotoxic activity in mice againstlipopolysaccharide and D-galactosamine induced hepatitis.With different doses of S. lappa, pretreatment of mice led torise in creatinine plasma levels in a dose dependent mannerand alanine transaminase, aspartate aminotransferaselevel as well. Whereas post treatment led to the limitedprogression of the hepatic damage which was induced bylipopolysaccharide and D-galactosamine. By the studiesit is proved that the root extract works against hepatotoxicactivity[25].
4.13. Miscellaneous
4.13.1. Antidiarrheal activityMethanol extract of S. lappa roots was investigated for
antidiarrheal activity on Wistar rats and it was observedthat administration of 100, 300 and 500 mg/kg body weight ofdose showed 26.33, 32.28 and 66.77% inhibition of diarrhea,respectively. The standard drug (loperamide) showedsignificant reduction (68.02%) in diarrheal stool at the dose of5 mg/kg body weight. The result of this study showed that thedose of 500 mg/kg body weight showed nearly similar effectto that of standard drug loperamide in reducing diarrhealstool.
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The methanol extract of S. lappa roots showed 32.28% inhibition of diarrhea at the dose of 300 mg/kg body weight.
So, these findings clearly showed that the MeOH extract ofS. lappa exhibited significant antidiarrheal activity[45].
4.13.2. Hypolipidaemic Aqueous extract of S. lappa was orally administered totwenty-seven rabbits at a dose of 2 mg/kg body weight and
showed significant hypolipidaemic effect. Reduction inserum cholesterol and serum triglycerides was also found tobe significant[18].
4.13.3. Resistance to pathogenic microorganisms S. lappa or its combination with other herbs could be usedclinically for the treatment of gastritis, gastric ulcer, skindiseases, refux esophagitis, hepatitis, diarrhea and someoral cavity diseases, which may be related to its capabilityto improve resistance to pathogenic microorganisms.
4.13.4. Resistance to Helicobacter pylori (H. pylori)
H. pylori is an important pathogenic microorganism thatcauses many diseases, including functional diseases of thedigestive tract (e.g., gastric cancer, gastritis and dyspepsia) as well as endocrine disorders and autoimmune[46]. S. lappa extract strongly inhibits all the strains tested with minimuminhibitory concentration value of approximately 40 mg/mL[47-49]. Various extracts of S. lappa was investigated for its
antibacterial potential by using five strains of H. pylori andit showed highest minimum inhibitory concentration at thedosage of 40 µg/mL[50].
4.13.5. Resistance to Streptococcus mutans (S. mutans)
S. mutans is the most important currently recognizedcariogenic bacteria[51], traditionally used for treatingoral cavity diseases such as tooth decay, bad breath, and
periodontitis[27], which proposed that S. lappa may inhibitS. mutans. In another study, the effects of ethanolic extractwere evaluated on the growth and acid production of S.mutans, as well as the synthesis and adherence of water-insoluble glucans[52]. Their results of this study showed that ethanolic extract
(0.5 mg/mL to 4 mg/mL) inhibited the growth and acidproduction of S. mutans, reduced the adherence of S.mutans, and inhibited the synthesis of water insolubleglucans. Results proved that S. lappa astonishinglyinhibited the cariogenic activity of S. mutans.
4.13.6. Resistance to other microorganisms The active ingredients of S. lappa inhibit the transfer andbinding of R plasmids in Shigella fexneri[50]. Moreover, theyinhibit the expression of the HBsAg as well as growth of
other microorganisms and pathogens[38,53]. Ethanolic extract of S. lappa was assessed forantimicrobial potential using S. mutans. The study showedthat the ethanolic extract caused significant ( P<0.05 ) inhibition on the growth. In addition, it also reduced theadherence of S. mutans[52].
The compounds KSR1-KSR4 were isolated by repeated
chromatography (column and high performance liquidchromatography ) of a flavonoid fraction obtained byprocessing of an ethanolic extract of powdered, dry S.lappa roots. Antifungal potential of S. lappa was assessed.
By using microdilution technique, nine fungal strainsi.e. Aspergillus niger, Aspergillus ochraceus, Aspergillus versicolor , Aspergillus flavus , Penicilium ochrochloron, Penicillium funiculosum, Trichoderma viride, Cladosporium
cladosporioides and Alternaria. KSR4 possessed the highestantifungal potential, while KSR3 showed medium activity.
Compounds KSR1 and KSR2, showed good activity[12].
4.13.7. Antiparasitic The activity of S. lappa against Trypanosoma cruzi,Clonorchis sinensis, and some nematodal infectionswere determined. Decoction of plant was given orallyinto Clonorchis sinensis infected rabbits and found to beeffective up to some extent[54]. In the children infected withthe respective worms, the efficacy of S. lappa was studiedon the basis of percentage reductions in the faecal eggs/
gram counts. In the doses, tested S. lappa did not produceany adverse side effects [55,56]. The methanolic extractof S. lappa was investigated in axenic cultures with theepimastigote form of Trypanosoma cruzi, clone Bra C15 C2,at 27 °C in F-29 medium at a concentration of 100 mg/mL.
It is proved that S. lappa extract exhibited antiparasiticactivity.
4.13.8. Antiviral activity S. lappa root extract was investigated for its potentialagainst HBV in human hepatoma Hep3B cells. Activecompounds isolated from S. lappa such as costunolideand dehydrocostus lactone suppressed the expression of
HBsAg with IC50 values of 1.0 and 2.0 mmol/L respectively.By northern blotting analysis, the suppression wasalso observed in HepA2 cell line, so it was confirmed
that compounds present in S. lappa root extract hadconsiderable activity against HBV[38].
5. Other uses
5.1. Perfumery
The fragrant oil obtained from S. lappa is very valuable inperfumery. Its odour slightly resembles with the oil of orris.It is also blends with other oriental perfumes in a lastingmanner [57].
5.2. Pesticidal
The root, containing both the essential oil and the
alkaloid, is a reliable insect repellant. In China, it is thebasis of incense, made into sticks which are burned in homeand in the temples for worship, and also serve through theirsmoke to keep gnats, mosquitoes, and other flying insects ata space. In India, the dried root yields brilliant fumigatorypastilles, which burn fairly well and as the Chinese joss-
sticks, it serves the same insectifugal function[58,59].
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6. Traditional uses
6.1. Ethnomedicinal uses
S. lappa is one of the most commercially viable species
among all the species of genus Saussurea. It is widely
utilized in various indigenous system of medicine all around
the world for treating variety of disorders such as tenesmus,
diarrhea, vomiting, dyspepsia, inflammation[60,61]. It is
also prescribed in irregular menstruation, tenesmus and
abdominal pain[20,62].
Medicinal properties of this plant are well documented
in traditional Chinese medicine, ayurvedic medicine and
the Tibetan system of medicine[63]. In the Handbook of
Traditional Tibetan Drugs, out of the 175 formulations it
was reported that S. lappa was one of the main ingredients
in 71 formulations[64]. The roots of S. lappa have a strong
and sweet aromatic odour with a bitter taste, and are used
in controlling bronchial asthma and as an antiseptic.
Preparations made from this species are also reported to
cure various diseases and conditions including ophthalmicconditions, fever, cough, paralysis, asthma, deaf, tridosha,
hysteria and headache[65,66].
The plant is prehistoric and well known about 2 500 years
ago. It is used in various ancient system of medicine such
as Unani, Ayurveda and Siddha[67]. In Indian traditionalsystems of medicine, S. lappa is used either in combination
with other drugs or as a single drug. The dried roots are
somewhat bitter in taste and grey to yellow in colour.
The essential oil obtained from roots is mostly used in
medicine[68]. Its roots are mainly used in asthma, cough
and also in treatment of chronic skin diseases, rheumatism
and cholera[69,70]. Different preparations of roots are used
by Ayurvedic physicians for the treatment of a range of
ailments like cold, flatulence, pruritus, gout, epilepsy,
headache, itching and leucoderma[71,72]. S. lappa is used as
an important medicine for gout, erysipelas and promotesspermatogenesis. In Tibetan medicine, the roots are
considered to have an acrid, sweet and bitter taste with a
neutral potency. S. lappa is one of the important ingredients
in several traditional Tibetan formulae that are used for
chronic inflammation of the lungs, chest congestion e.g.
hippophae and eliminator of lung inflammation[73]. The
roots possess carminative, anthelmintic, analgesic and
emmenagogic properties. It stimulates the brain and cures
blood, liver and kidney disorders. Different preparations
of S. lappa are prescribed in helminthic infestations,
convulsions, gas, leprosy, cold, persistant hiccups,
tuberculosis, quartan malaria, rheumatism, intestinal
carcinogenesis and edema[26,74]. It is also used traditionally
to cure skin diseases such as scabies, ringworm, bruises and
cuts[75-77].
6.2. Ethnoveternary uses
Locally, it is used against the heart diseases of cattle[78].
6.3. Other uses
The powdered roots are sprinkled over crops as
insecticides. The roots are used as insecticide to protect
woollen fabrics, and as incense. The upper parts of its plants
are used as fuel and fodder and dried leaves are smoked as
tobacco[43]. It is also used to improve complexion, as a hair
wash to kill lice and to turn grey hair to black[62,79]. Other
traditional applications of S. lappa are shown in Table 2.
Table 2
Traditional methods of application of S. lappa.
Conditions Method of applications
Stomachache Root powder is taken with water. Decoction of root is taken. Root powder is roasted in mustard oil and the paste is applied on stomach
Headache Oil heated with root is applied
Cough and cold Root powder is taken with warm water
Throat infection Root is chewed
Backache and chest pain Root powder is taken with milk/decoction of root powder. Oil heated with root is massaged the affected area
Rheumatism and painful joints Root is roasted in ghee/butter, powdered and taken with milk. The above mentioned ghee/ butter is rubbed on the affected area
and bandaged to keep warm.
Scanty urination Jaggery is mixed in the decoction of root powder which is then taken. Paste of root powder is applied on the stomach below the naval.
Skin rashes formed after
insect bite
Root powder is roasted in ghee/butter and the ghee/butter is applied on the affected area
Exhaustion Pieces of root are burnt in hookah and the smoke inhaled
Lustre and growth of hair Hair is washed with decoction. Mustard oil is heated with root powder and the oil used as topical application on hair
Pustules Fine root powder is dusted on the wound. Mustard oil is heated with root powder and the oil is applied and bandaged
Fainting spells Root is rubbed in water and the water is used a nasal drops Fine powder of root is used for sneezing.
General weakness fatigue Root is boiled in milk and the milk is taken twice daily
Piles Root are taken along with the ‘Vacha’ (Acorus calamus) roots
Epilepsy The roots are taken with honey
Headache Paste of the root is applied
General weakness (as Rasayana) Root powder ingested with cow’s milk and cow’s ghee
Scalp scabies Essential oil of root is applied
Typhoid fever Decoction of root is taken
Persistant hiccups Root powder is ingested
Leprosy Root powder is ingested
Cold Decoction of root is taken
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7. Trade of S. lappa
In the Himalaya along with the dominant high altitudegenera for high number of endemic species, Saussurea isthe second largest genera (35 spp.)[70]. As already mentionedS. lappa has great demand in pharmaceutical industry butduring the last decade, the species for its threatened statushas been more popularized globally. In past, due to high
market demand and unchecked exploitation, the specieswas reported to be extinct in many pockets in the wild[75]. Inorder to conserve the species and to fulfil the growing traderequirements, commercial cultivation of S. lappa was takenup in various regions. It is now commercially grown on aextensive scale, from Kashmir to Garwhal in Uttar Pradesh(United Provinces) in the forested areas similar to where itgrows naturally.
It has been introduced and cultivated in threesouthernmost provinces of China. Trade has been significantover a long period. For shipment to Arabia and the RedSea ports, large amount of the root have customarily beenexported from Kashmir to Bombay and Calcutta for use
chiefly in perfumery and medicine. There has also beensubstantial movement of the product within China. Globally,China has exported a total of 1 024 tons of roots and derivatesoverall since 1983 to 2009 and India exported a total of 266 tons during the same period.
Presently, France is one of the leading importers of theroot. Medicinally, the drug is known as radix saussureaelappae and the product has been marketed under the namescostus root and costus root oil, Putchuk or Patchak (theBengali name), and now in India as Kuth.
8. Challenges in conservation and sustainable use of S.lappa
S. lappa is an important plant, used widely in traditionaland herbal medicine, also utilized in modern medicine.Due to high demand, most of the natural populations ofthe species are either have been extirpated or are underdestructive harvesting, therefore availability of this importantplant is decreasing in the wild day by day. S. lappa isendemic to a geographically limited part of the Himalayas,and grows on moist slopes at altitudes of 2 600-4 000 m[80].Apart from the restricted distribution, the harvesting ofwhole plant is one of the reasons for being threatened. Thiscritically endangered species is enlisted in Appendix I ofConvention on International Trade in Endangered Species
of Wild Fauna and Flora (CITES). S. lappa is one of the 37 Himalayan endangered medicinal plants that have beenprioritized for in situ and ex situ conservation[81]. Because of an endemic species to the Himalaya,the distribution of this species is fairly restricted totremendously narrow geographical range[82], which makesit more vulnerable to extinction. Being an endangeredspecies[56,83], it was enlisted in Appendix I of CITES. Tradeof S. lappa is strictly prohibited under Foreign TradeDevelopment Act-1992. It is first listed in Appendix II ofCITES on 1.7.1975 as S. lappa and afterward up listed toAppendix I in 1985. Due to the various known uses, S. lappa is in high demand
both internationally and at the local level. It is one of the
most commercially used Appendix I CITES species forvarious complaints in numerous indigenous systems ofmedicine[2,84]. Saussurea costus has been in high demandin the pharmaceutical industry. During the last decade,the species has been even more popularized due to itsthreatened status globally. Due to uncontrolled exploitationof the species and high market demand, it was reported tobe extinct in many pockets in the wild.
9. The way forward
A multi-branched approach to maintain the resource basethat includes in situ and ex situ conservation and selection ofbetter-quality genotypes followed by their multiplication (byboth biotechnological and conventional approaches) couldwell provide available solution to the problem.
9.1. Biotechnological interventions
Since the value of medicinal plants depends on the amount
of the active principle present in it, it would be enviableto carry out cultivation of superior clones (recognized as‘elite’). These elites can be acknowledged by chemo-profiling and by the use of different molecular markertechniques. Thereafter, either or both conventional methodsof propagation and tissue culture techniques can be used tomultiply the plant for raising commercial plantations as wellas for conservation. For the species which are difficult to regenerate byconventional methods and due to over exploitation bydestructive harvesting, their populations have decreased.Micropropagation can be used as a feasible alternative. It isalso useful in terms of the active principles present. There islots of variability, and elites have been recognized based ontheir potential for yielding higher amount of active principle.
This technology can successfully be used to meet upthe growing demand for clonally uniform elite plants ofS. lappa. For large-scale production of plant cells fromwhich secondary metabolites could be extracted besidesmicropropagation, cell suspension culture systems could beused. Cell culture systems have numerous major advantagesas it is independent of space constraints, geographical andseasonal variations and offers a defined production systemensuring an uninterrupted supply of good quality productsof high yield. It also allows for preset management of cellgrowth and regulation of metabolite processes which in turn
will improve productivity and lessen labour costs.
9.2. Cultivation practices
Cultivation has several advantages over collection fromthe wild. Due to environmental and genetic differences, wildharvested plants usually vary in quality and consistencywhich dangerously compromise economic returns. Similarly,local environmental conditions strongly control the efficacyof medicinal plants. A plant might fail to produce the activeconstituents of concern since temperature, day length,rainfall and soil characteristics are some of the factors thathave serious effects on the potency of medicinal plants.
Before arriving at suitable agro-techniques, these are some
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parameters that need to be studied well. Biopesticides,better-quality planting material produced throughmicropropagation in combination with use of bio-fertilizers(mycorrhiza) and improved agro-techniques would enhancethe yields even further and generate constantly higherfinancial returns to the growers.
9.3. Post-harvest handling
The quality of medicinal plants also depends on themanner of post-harvest handling. It is observed that duringharvesting, handling and storage, the collectors of herbalmaterial pay less consideration to quality of material. Ithas been reported that stored herbal drug samples veryfrequently harbour mycotoxin producing fungi.
Above the acceptable limit fixed by the World HealthOrganization for human consumption, such herbal drugscontaining mycotoxins above would be rejected in theglobal market. Therefore, efforts should be made in order toencourage sustainable management of medicinal plants atthe community level itself by highlighting the improvement
of collection, cultivation and marketing practices.
10. Conclusion
S. lappa is a renowned medicinal plant that is oftenprescribed in various indigenous systems of medicineschiefly those of India, China, Tibet and Korea. It is usedfor treatment of many ailments in allopathic and herbalsystem of medicine such as chronic skin diseases,rheumatism, cholera, cough and cold, persistant hiccups,stomachache, toothache, typhoid fever, rheumatism,quartan malaria, leprosy etc. Various active compoundsisolated from S. lappa are reported to have medicinalproperties. The major components are sesquiterpenelactones such as costunolide and dehydrocostus lactone. Ithas various biological activities such as anticancer, anti-inflammatory, hepatoprotective, anti-ulcer and cholagogic,anticonvulsant, imunomodulator, gastroprotective,angiogenesis, hypoglycaemic, spasmolytic, anti-hepatotoxic,antidiarrheal, hypolipidaemic, antiparasitic, antimicrobialand antiviral activity. It is also considered as an importantplant in terms of veterinary medicine and used againstthe heart diseases of cattle. The oil obtained from S.lappa is very valuable and used in perfumery. The root isconsidered as a reliable insect repellant as their smoke tokeep gnats, mosquitoes, and other flying insects at a space.
The preliminary experiments justify the reputation of thedrug as a useful remedy against cancer [26-29]. The resultsof the different studies have empirically designated thatS. lappa is effectual as an anti-inflammatory agent. Totalmethanol extract of S. lappa showed compelling inhibitoryeffect on the formation of TNF-alpha, a pro-inflammatorycytokine, in murine macrophage-like cell (RAW 264.7 cells).The activity guided purification resulted in the isolation ofthree sesquiterpene lactones, reynosin, cynaropicrin andsantamarine, which in a dose dependent manner inhibitedTNF-alpha production. Inflammation has been closelyrelated to rheumatism. Therefore, the anti-inflammatoryproperties of S. lappa may be the reason for its ethnomedical
use in rheumatism. Some of the chemical constituents of S.
lappa have been found to have the potential to be developedas bioactive molecules. Costunolide and cynaropicrinhave been identified as latent anticancer agents. Similarly,cynaropicrin has been identified as the principal inhibitorof TNF-alpha. Dehydrocostus lactone and costunolidehave been reported to display strong suppressive effect onthe expression of HBsAg in human hepatoma Hep3B cellsand therefore have the potential to be developed as anti-
HBV drugs. Although the published confirmation to datesupports the safety and perhaps the efficiency of S. lappa, the quality of the evidence is limited; active constituents,physiological pathways, pharmacokinetics, bioavailability,and importance to human health are not known withsufficient detail or assurance. Since S. lappa has variousmedicinal applications, that’s why more in vitro, clinicaland pathological studies are required to investigate theunexploited potential of this plant. As already mentioned, S. lappa has great demand inpharmaceutical industry. So due to high demand, mostof the natural populations of the species are either havebeen extirpated or are under destructive harvesting. It is
endemic to a geographically limited part of the Himalayas.This critically endangered species is enlisted in AppendixI of CITES. However, a multi-branched approach includingin situ and ex situ conservation and selection of better-quality genotypes followed by their multiplication could wellprovide available solution to the problem.
Conflict of interest statement
We declare that we have no conflict of interest.
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