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Asian Pac J Trop Med 2014; 7(Suppl 1): S60-S69

Contents lists available at ScienceDirect

Asian Pacific Journal of Tropical Medicine


journal homepage:www.elsevier.com/locate/apjtm

Document heading

doi: 10.1016/S1995-7645(14)60204-2

review of therapeutic potential of Saussurea lappa-An endangered


plant from Himalaya

Kulsoom Zahara, Shaista Tabassum, Sidra Sabir, Muhammad Arshad, Rahmatullah Qureshi, Muhammad Shoaib Amjad,
Sunbal Khalil Chaudhari*
Department of Botany, PMAS Arid Agriculture University Rawalpindi, Pakistan

ARTICLE INFO
Article history:
Received 30 Jun 2014
Received in revised form 23 Jul 2014
Accepted 10 Aug 2014
Available online 17 Sep 2014

Keywords:

Saussurea lappa
Himalaya
Phytochemicals
Bioactivities
Clinical research

ABSTRACT
T here are 300 known Saussurea species. A mong them, Saussurea lappa ( S. lappa ) is a
representative perennial herb, globally distributed across Himalaya region. S. lappa has been
traditionally used in medicines without obvious adverse effects. Despite significant progress in

phytochemical and biological analyses of S. lappa over the past few years, inclusive and critical
reviews of this plant are anachronistic or quite limited in scope. The present review aims to
summarize 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. In
addition 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 constituent
phytochemicals 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. Although
some progress has been made, further scrupulous efforts are required to investigate the individual
compounds isolated from S. lappa to validate and understand its traditional uses and develop
clinical applications. The present review offers preliminary information and gives direction for
further basic and clinical research into this plant.

1. Introduction
1.1. Geographical distribution
Saussurea lappa (S. lappa) is indigenous to
India, Pakistan and China, where it grows in
the H imalaya region at 2 5 0 0 - 3 5 0 0 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 root
is 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
*Corresponding author: Sunbal Khalil Chaudhari, Department of Botany, PMAS Arid
Agriculture University Rawalpindi, Pakistan.
E-mail: khalilsunbal@yahoo.com

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 been
isolated. 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] ,
-hydroxydehydrocostus lactone, -hydroxydehydrocostus
lactone, lappadilactone[4], mokko lactone, betulinic acid,
betulinic acid methyl ester[5], cynaropicrin, reynosin,
santamarine[6], saussureamines A-C[7], -cyclocostunolide,
alantolactone, isoalantolactone[8], isodihydrocostunolide,
-cyclocostunolide [9] , 1 -hydroxy arbusculin A [5] ,

Kulsoom Zahara et al./Asian Pac J Trop Med 2014; 7(Suppl 1): S60-S69

arbusculin B[10], saussureal and so on[11].


Table 1
Taxonomic Hierarchy of S. lappa C.B. Clarke.
Kingdom
Subkingdom
Infrakingdom
Division
Subdivision
Infradivision
Class
Superorder
Order
Family
Genus
Species

Plantae
Viridaeplantae
Streptophyta
Tracheophyta
Spermatophytina
Angiospermae
Magnoliopsida
Asteranae
Asterales
Asteraceae
Saussurea DC.
S. lappa C.B. Clarke

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cedren-13-ol (5.06%) and -curcumene (4.33%). However,


-costol (13.55%) and -elemene (12.69%), -selinene (5.02%),
-selinene ( 4 . 47 % ) , -costol ( 4 . 02 % ) , 4 -terpinol ( 3 . 38 % ) ,
elemol (3.21%), -ionone (3.13%), -elemene (3.00%), (-)-elemene (2.08%), p-cymene (1.96%) and 2--pinene (1.57%),
( - ) - -selinene, ( + ) -selina- 4 , 11 -diene, ( - ) - -transbergamotene, (-)--costol, (+)--costol, (-)-elema-1,3,11
(13 )-trien- 12 -ol, (-)--costal, (+)--costal, (-)-elema-

1,3,11(13)-trien-12-al, (-)-(E)-trans-bergamota-2,12-dien14-al, (-)-ar-curcumene, (-)-caryophyllene oxide and 12-m

ethoxydihydrodehydrocostuslactone were also reported[14,15].


However, in the other reported studies, the proportion
of all these compounds greatly differs. Existing variations
in the composition of S. lappa essential oil may be due to
various factors related to ecotype, phenophases, chemotype
and variations in environment conditions such as relative
humidity, temperature, photoperiod and irradiance.
Furthermore, the chemistry of secondary metabolites of
plants may also be affected by genetic background[16].
4. Pharmacology
S. lappa is a medicinally important plant. V arious
active compounds isolated from plant are reported to
have medicinal properties e.g. the major components
are sesquiterpene lactones such as costunolide and
dehydrocostus lactone. S. lappa possesses various
bioactivities 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 [23], a n t i i n f l a m m a t o r y [24] a n d
antihepatotoxic[25].
4.1. Anticancer/antitumor

Figure 1. S. lappa floral part.

S. lappa has three anthraquinone compounds, namely,


aloeemodin- 8 - O - -d-glucopyranoside, rhein- 8 - O -d- glucopyranoside, and chrysophanol. Four favonoid
glycosides have antibacterial function[12]. Shikokiols have
antitumor activity[13], whereas chlorogenic acid prevents
oxidization.
3. Costus oil
The oil extracted from the roots of S. lappa is known as
costus oil, which is used in the preparation of hair oil and in
high quality perfumes. Costus oil is pale yellow to brownish
in color and is also said to be valuable in treating leprosy.
In a recent study, 39 components have been identified
from the essential oil of S. lappa roots. The chief compounds
were dehydrocostus lactone (46.75%), costunolide (9.26%), 8-

Costunolide (isolated from root of S. lappa) was studied


for its effect and supposed pathways of action on the
induction of apoptosis in HL-60 human leukemia cells.
U sing apoptosis analysis, evaluation of mitochondrial
membrane potentials and measurement of reactive oxygen
species (ROS), it was proved that costunolide was a potent
apoptosis inducer, and by ROS generation aiding its activity,
it induced mitochondrial permeability transition and
released cytochrome C to the cytosol. In cells treated with
costunolide, an antioxidant N-acetylcystein is responsible
for blocking the mitochondrial alteration, ROS production,
and consequent apoptotic cell death. Costunolide stimulates
the ROS-mediated mitochondrial permeability transition and
resultant cytochromes C release[26].
The hexane extract of S. lappa was investigated for the
chemo preventive potential in autonomous androgen prostate
cancer and apoptosis induction in DU145 cells. Results of
this study showed that dehydrocostus lactone isolated from
the hexane extract of S. lappa induced apoptosis in cell lines
of DU145 human autonomous androgen prostate cancer and
inhibited the cell growth[27].
C ynaropicrin isolated from S. lappa was assessed
for its immunomodulatory effects on cytokine release,
immunosuppressive effects, and nitric oxide production.

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C ynaropicrin repressed J urkat T , E ol- 1 and U 937 cell


lines in a dose-dependent manner with IC50 values of 2.36,
10.90 and 3.11 mol/L respectively. Further, by means of

DNA disintegration, cell cycle arrest and morphological


analysis via U937 cells, its cytotoxic effect is studied. When
cynaropicrin is treated in combination with ROS scavengers
rottlerin, N-acetyl-L-cysteine or L-cysteine repressed the
cynaropicrin mediated cytotoxicity. The results showed that
cynaropicrin was more cytotoxic toward leukocyte derived
cancer cells than fibroblasts[28].
Costunolide is a sesquiterpene lactone isolated from S.
lappa proved to have effect on carcinogenesis via reporter
gene assay, persuaded by a tumor endorsing phorbol ester
12-O-tetradecanoylphorbol-13-acetate at cellular level.
The activity of nitric oxide synthase is amplified by tumor
promoting phorbol ester 12-O-tetradecanoylphorbol-13acetate which consecutively repressed by costunolide with
the IC50 value of 2 mmol/L[29].
In another study, the effect of costunolide on telomerase
inhibitory activity was investigated on MDA - MB - 231 ,
MCF-7 cells which confirmed the hindering activity[30].
Dehydrocostuslactone is another sesquiterpene lactone
isolated from S. lappa and investigated for anticancer
potential for non lung cancer cell lines, for example
A549, NCI-H460 and NCI-H520 and its activity have been
confirmed[31].
E thanolic extract of S. lappa showed that apoptosis
followed in a dose and time dependent manner such as 80
g/mL and 48 h which gives confirmation for the treatment
of gastric cancer by S. lappa[20].
Hepatocellular carcinoma activity of dehydrocostuslactone
was evaluated by in vitro assays, such as cell proliferation
assay, immunoblot assay, assay for kinase activity,
apoptosis and caspase activity assay. By using transmission
electron microscopy, the in vivo analysis was done. The
results proved its anticancer activity at the IC50 values 16.7
and 18.8 mol/L[32].
C ostunolide and dehydrocostus lactone had been
isolated from different extracts of S. lappa. Costunolide
and dehydrocostus lactone confirmed the cytolytic activity
at ID 50 of 3 . 6 - 10 mol/ L . A t 13 . 6 mol/ L , costunolide
completely inhibited the granule exocytosis in a dosedependent manner and even repressed the amplification
in the tyrosine phosphorylation at different concentrations.
Therefore, results disclosed that the costunolide performed
in a mechanistic means by preventing the increase in the
phosphorylation of tyrosine[33].
Costunolide inhibits the vascular endothelial growth
factor (VEGF)-induced chemotaxis of human umbilical vein
endothelial cells in a dose-dependent manner. It was also
found to selectively inhibit the endothelial cell proliferation
induced by VEGF. The result of this study showed that
by blocking the angiogenic factor signaling pathway,
costunolide might inhibit angiogenesis. VEGF interacts
with its cognate receptors, KDR/Flk-1 and Flt-1, and exerts
its angiogenic effect. Costunolide is found to inhibit the
autophosphorylation of KDR/Flk-1 without affecting that
of Flt-1. These results suggest that costunolide may prove
to be useful for the development of a new angiogenesis
inhibitor[34]. C-17 polyene alcohol isolated from S. lappa

exhibited moderate cytotoxicities against the human tumor


cell 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 frequently
used 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 inhibition
on the cytokine induced neutrophil chemotactic factor
induction[35].
Ethanolic extract of S. lappa was studied at a dose range
of 50-200 mg/kg, for the acute and chronic inflammation
induced in both mice and rats. The result of this study
revealed that the extract showed considerable values for
anti-inflammatory activity through carrageenan induced
paw edema and peritonitis animal models[36]. Costunolide
was investigated for anti-inflammatory activity and it
was observed that costunolide hindered the protein and
m RNA expression of interleukin- 1 b. B y means of an
electrophoretic mobility shift assay, it was confirmed that
it also concealed the AP-1 transcription activity. So, all
these activities proved the anti-inflammatory activity of
costunolide[37].
The potential of dehydrocostus lactone for the oxidative
osteoblast damage was investigated and showed
considerable increase in the osteoblast growth and
hydrogen peroxide. At 0.4-2 g/mL of dose, the factors
for example calcium deposition, collagen and alkaline
phosphatase were improved. These results confirmed that
dehydrocostus lactone compound had potential to be used
against oxidative osteoblast damage[5].
At the doses of 50, 100 and 200 mg/kg, the ethanolic
extracts of S. lappa were assessed for their action on acute
and chronic inflammation and at 50-200 mg/kg it showed
considerable inhibition on carrageenan induced paw
edema[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 surface
antigen (HBsAg). It is proved that these compounds inhibit
the HBsAg production by Hep3B cells with IC50 of 1.0 and 2.0
mol/L, respectively. Northern blotting analysis proved that
they suppress (HBsAg) gene expression mainly at the mRNA
level. Moreover, in another human hepatoma cell line Hep
A2 (derived from Hep G2 cells) by transfecting a tandemly
repeat hepatitis B virus (HBV) DNA, the inhibitory effect of
costunolide on replication of human liver cells was studied.
Results showed that both costunolide and dehydrocostus
lactone had the tendency to be developed as potent anti
HBV drugs in the future[38].

4.4. Anti-ulcer and cholagogic


The acetone extract of S. lappa and costunolide showed
cholagogic effect and inhibitory effect on the formation of

Kulsoom Zahara et al./Asian Pac J Trop Med 2014; 7(Suppl 1): S60-S69

gastric ulcer in mice[39]. The serum gastrin, variation in


gastric acidity output, and plasma somatostatin concentration
were observed during S. lappa decoction perfusion into
the stomach of patients with chronic superficial gastritis
and results revealed that the decoction could increase
the endogenous motilin release and accelerate the gastric
emptying[38]. S. lappa is one of the major ingredients of UL409, a formulation which possesses anti-ulcer activity and
the activity is may be due to the intonation of defensive
factors by improvement in gastric cytoprotection[40,41].
Antiulcer activity of herbal formulation of S. lappa was
tested in Wistar rats and male pigs. Orally 600 mg/kg drug
was given. The drug showed significant effect in gastric
ulceration induced by alcohol and aspirin, cold resistant
induced ulcerations and duodenal ulcer models. It amplified
the mucus discharge in all so it was proved to be an
antiulcer agent[40].
4.5. Imunomodulator

4.9. Angiogenesis effect

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E ndothelial cell proliferation ( induced by vascular


endothelia growth factor) is reported to be repressed by
costunolide (isolated from S. lappa root). Studies proved
that the chemotaxis induced by vascular endothelia
growth factor of human umbilical vein endothelial cells
was noticeably inhibited at IC50 of 3.4 mol/L. Similarly by
in vivo method the neo-vascularisation of mouse corneal
stimulated by vascular endothelia growth factor is repoted
to be inhibited at a dosage of 100 mg/kg/day. Inhibition of
vascular endothelia growth factor on VEGFR KDR/Flk-1 was
also proved through signaling pathway[34].

4.10. Hypoglycaemic
When a comprehensive examination and clinical study on
potent hypoglycemic plants of different regions from India
was undertaken, S. lappa was found effective for obese
diabetes[18].

Costunolide and dehydrocostus lactone act as inhibitors


of killing activity of cytotoxic T lymphocytes (CTL). Through
preventing the increase in tyrosine phosphorylation,
constunolide inhibited the killing activity of CTL in response
to the crosslinking of T cell receptors as inhibitors of the
killing function of CTL and the induction of intercellular
adhesion molecule- 1 , dehydrocostus lactone from S.
lappa and other guaianolides were examined for their
structure activity relationship[33]. It was confirmed that the
guaianolides moiety exhibited considerable inhibitory effects
towards the induction of intercellular adhesion molecule-1
and killing function of CTL[42].

From studies, it was proved that S. lappa was significantly


able to relax the contraction induced by carbachol (30 mol/
L). S. lappa has been reported to have antiperoxidative
effects possibly due to the presence of sesquiterpene
lactones. It is known to suppress contractions in guniea-pig
aorta. Sesquiterpenes are recognized to stimulate the sGC
which stimulates extrusion of K+ ions and thereby reduces
intrinsic Ca++ ions through activation of cGMP and PKG
pathway, leading to relaxation of smooth muscles[32].

4.6. Anticonvulsant activity

4.12. Anti-hepatotoxic activity

Different extracts of S. lappa root were evaluated for the


anticonvulsant activity by picrotoxin-induced convulsions,
pentylenetetrazole and maximal electroshock tests
performed in mice. It was proved that the petroleum extract
of S. lappa roots showed potent anticonvulsant activity at a
dose of 100 and 300 mg/kg[43].

Aqueous and methanolic extracts of S. lappa root were


investigated for hepatotoxic activity in mice against
lipopolysaccharide and D-galactosamine induced hepatitis.
With different doses of S. lappa, pretreatment of mice led to
rise in creatinine plasma levels in a dose dependent manner
and alanine transaminase, aspartate aminotransferase
level as well. Whereas post treatment led to the limited
progression of the hepatic damage which was induced by
lipopolysaccharide and D-galactosamine. By the studies
it is proved that the root extract works against hepatotoxic
activity[25].

4.7. Gastric function


Decoction of S. lappa was given to patients affected with
persistent superficial gastritis and checked for difference
in factors such as serum gastrin, gastric acidity and plasma
somatostatin. Decoction of S. lappa was also given to five
healthy volunteers. It was observed that it sped up the
gastric 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 lactone
isolated from the methanolic extract of S. lappa showed the
gastro-protective effect in rats on acidified ethanol induced
gastric mucosal lesions in a dose dependent manner (5 and
10 mg/kg)[44].

4.11. Spasmolytic activity

4.13. Miscellaneous
4.13.1. Antidiarrheal activity
Methanol extract of S. lappa roots was investigated for
antidiarrheal activity on Wistar rats and it was observed
that administration of 100, 300 and 500 mg/kg body weight of
dose showed 26.33, 32.28 and 66.77% inhibition of diarrhea,
respectively. T he standard drug ( loperamide ) showed
significant reduction (68.02%) in diarrheal stool at the dose of
5 mg/kg body weight. The result of this study showed that the
dose of 500 mg/kg body weight showed nearly similar effect
to that of standard drug loperamide in reducing diarrheal
stool.

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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 of
S. lappa exhibited significant antidiarrheal activity[45].

4.13.2. Hypolipidaemic
Aqueous extract of S. lappa was orally administered to
twenty-seven rabbits at a dose of 2 mg/kg body weight and
showed significant hypolipidaemic effect. Reduction in
serum cholesterol and serum triglycerides was also found to
be significant[18].
4.13.3. Resistance to pathogenic microorganisms
S. lappa or its combination with other herbs could be used
clinically for the treatment of gastritis, gastric ulcer, skin
diseases, refux esophagitis, hepatitis, diarrhea and some
oral cavity diseases, which may be related to its capability
to improve resistance to pathogenic microorganisms.
4.13.4. Resistance to Helicobacter pylori (H. pylori)
H. pylori is an important pathogenic microorganism that
causes many diseases, including functional diseases of the
digestive 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 minimum
inhibitory concentration value of approximately 40 mg/
mL[47-49].
V arious extracts of S. lappa was investigated for its
antibacterial potential by using five strains of H. pylori and
it showed highest minimum inhibitory concentration at the
dosage of 40 g/mL[50].
4.13.5. Resistance to Streptococcus mutans (S. mutans)
S. mutans is the most important currently recognized
cariogenic bacteria [51], traditionally used for treating
oral cavity diseases such as tooth decay, bad breath, and
periodontitis[27], which proposed that S. lappa may inhibit
S. mutans. In another study, the effects of ethanolic extract
were evaluated on the growth and acid production of S.
mutans, as well as the synthesis and adherence of waterinsoluble glucans[52].
Their results of this study showed that ethanolic extract
( 0 . 5 mg/m L to 4 mg/m L ) inhibited the growth and acid
production of S. mutans, reduced the adherence of S.
mutans, and inhibited the synthesis of water insoluble
glucans. R esults proved that S. lappa astonishingly
inhibited the cariogenic activity of S. mutans.
4.13.6. Resistance to other microorganisms
The active ingredients of S. lappa inhibit the transfer and
binding of R plasmids in Shigella fexneri[50]. Moreover, they
inhibit the expression of the HBsAg as well as growth of
other microorganisms and pathogens[38,53].
E thanolic extract of S. lappa was assessed for
antimicrobial potential using S. mutans. The study showed
that the ethanolic extract caused significant ( P< 0 . 05 )
inhibition on the growth. In addition, it also reduced the
adherence of S. mutans[52].
The compounds KSR1-KSR4 were isolated by repeated

chromatography ( column and high performance liquid


chromatography ) of a flavonoid fraction obtained by
processing of an ethanolic extract of powdered, dry S.
lappa roots. Antifungal potential of S. lappa was assessed.
B y using microdilution technique, nine fungal strains
i.e. Aspergillus niger, Aspergillus ochraceus, Aspergillus
versicolor, Aspergillus flavus, Penicilium ochrochloron,
Penicillium funiculosum, Trichoderma viride, Cladosporium
cladosporioides and Alternaria. KSR4 possessed the highest
antifungal potential, while KSR3 showed medium activity.
Compounds KSR1 and KSR2, showed good activity[12].
4.13.7. Antiparasitic
T he activity of S. lappa against Trypanosoma cruzi,
Clonorchis sinensis, and some nematodal infections
were determined. D ecoction of plant was given orally
into Clonorchis sinensis infected rabbits and found to be
effective up to some extent[54]. In the children infected with
the respective worms, the efficacy of S. lappa was studied
on the basis of percentage reductions in the faecal eggs/
gram counts. In the doses, tested S. lappa did not produce
any adverse side effects [55,56]. T he methanolic extract
of S. lappa was investigated in axenic cultures with the
epimastigote 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 antiparasitic
activity.
4.13.8. Antiviral activity
S. lappa root extract was investigated for its potential
against HBV in human hepatoma H ep 3 B cells. A ctive
compounds isolated from S. lappa such as costunolide
and dehydrocostus lactone suppressed the expression of
HBsAg with IC50 values of 1.0 and 2.0 mmol/L respectively.
B y northern blotting analysis, the suppression was
also observed in H ep A 2 cell line, so it was confirmed
that compounds present in S. lappa root extract had
considerable activity against HBV[38].
5. Other uses
5.1. Perfumery
The fragrant oil obtained from S. lappa is very valuable in
perfumery. Its odour slightly resembles with the oil of orris.
It is also blends with other oriental perfumes in a lasting
manner[57].

5.2. Pesticidal
T he root, containing both the essential oil and the
alkaloid, is a reliable insect repellant. In China, it is the
basis of incense, made into sticks which are burned in home
and in the temples for worship, and also serve through their
smoke to keep gnats, mosquitoes, and other flying insects at
a space. In India, the dried root yields brilliant fumigatory
pastilles, which burn fairly well and as the Chinese josssticks, it serves the same insectifugal function[58,59].

Kulsoom Zahara et al./Asian Pac J Trop Med 2014; 7(Suppl 1): S60-S69

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 ophthalmic
conditions, 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 traditional
systems 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

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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 promotes
spermatogenesis. I n T ibetan 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


T he 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

Headache

Oil heated with root is applied

Stomachache
Cough and cold

Throat infection

Backache and chest pain

Rheumatism and painful joints

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
Root powder is taken with warm water
Root is chewed

Root powder is taken with milk/decoction of root powder. Oil heated with root is massaged the affected area

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.
S kin rashes formed after Root powder is roasted in ghee/butter and the ghee/butter is applied on the affected area
insect bite
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 cows milk and cows 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 altitude
genera for high number of endemic species, Saussurea is
the second largest genera (35 spp.)[70]. As already mentioned
S. lappa has great demand in pharmaceutical industry but
during the last decade, the species for its threatened status
has been more popularized globally. In past, due to high
market demand and unchecked exploitation, the species
was reported to be extinct in many pockets in the wild[75]. In
order to conserve the species and to fulfil the growing trade
requirements, commercial cultivation of S. lappa was taken
up in various regions. It is now commercially grown on a
extensive scale, from Kashmir to Garwhal in Uttar Pradesh
(United Provinces) in the forested areas similar to where it
grows naturally.
I t has been introduced and cultivated in three
southernmost provinces of China. Trade has been significant
over a long period. For shipment to Arabia and the Red
Sea ports, large amount of the root have customarily been
exported from Kashmir to Bombay and Calcutta for use
chiefly in perfumery and medicine. There has also been
substantial movement of the product within China. Globally,
China has exported a total of 1 024 tons of roots and derivates
overall 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 the
root. Medicinally, the drug is known as radix saussureae
lappae and the product has been marketed under the names
costus root and costus root oil, Putchuk or Patchak (the
Bengali 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 traditional
and herbal medicine, also utilized in modern medicine.
Due to high demand, most of the natural populations of
the species are either have been extirpated or are under
destructive harvesting, therefore availability of this important
plant is decreasing in the wild day by day. S. lappa is
endemic 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 of
whole plant is one of the reasons for being threatened. This
critically endangered species is enlisted in Appendix I of
Convention 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 been
prioritized for in situ and ex situ conservation[81].
B ecause of an endemic species to the H imalaya,
the distribution of this species is fairly restricted to
tremendously narrow geographical range[82], which makes
it more vulnerable to extinction. Being an endangered
species[56,83], it was enlisted in Appendix I of CITES. Trade
of S. lappa is strictly prohibited under F oreign T rade
Development Act-1992. It is first listed in Appendix II of
CITES on 1.7.1975 as S. lappa and afterward up listed to
Appendix 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 A ppendix I CITES species for


various complaints in numerous indigenous systems of
medicine[2,84]. Saussurea costus has been in high demand
in the pharmaceutical industry. During the last decade,
the species has been even more popularized due to its
threatened status globally. Due to uncontrolled exploitation
of the species and high market demand, it was reported to
be extinct in many pockets in the wild.
9. The way forward
A multi-branched approach to maintain the resource base
that includes in situ and ex situ conservation and selection of
better-quality genotypes followed by their multiplication (by
both biotechnological and conventional approaches) could
well 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 enviable
to carry out cultivation of superior clones (recognized as
elite ) . T hese elites can be acknowledged by chemoprofiling and by the use of different molecular marker
techniques. Thereafter, either or both conventional methods
of propagation and tissue culture techniques can be used to
multiply the plant for raising commercial plantations as well
as for conservation.
F or the species which are difficult to regenerate by
conventional methods and due to over exploitation by
destructive harvesting, their populations have decreased.
Micropropagation can be used as a feasible alternative. It is
also useful in terms of the active principles present. There is
lots of variability, and elites have been recognized based on
their potential for yielding higher amount of active principle.
This technology can successfully be used to meet up
the growing demand for clonally uniform elite plants of
S. lappa. For large-scale production of plant cells from
which secondary metabolites could be extracted besides
micropropagation, cell suspension culture systems could be
used.
Cell culture systems have numerous major advantages
as it is independent of space constraints, geographical and
seasonal variations and offers a defined production system
ensuring an uninterrupted supply of good quality products
of high yield. It also allows for preset management of cell
growth 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 from


the wild. Due to environmental and genetic differences, wild
harvested plants usually vary in quality and consistency
which dangerously compromise economic returns. Similarly,
local environmental conditions strongly control the efficacy
of medicinal plants. A plant might fail to produce the active
constituents of concern since temperature, day length,
rainfall and soil characteristics are some of the factors that
have serious effects on the potency of medicinal plants.
Before arriving at suitable agro-techniques, these are some

Kulsoom Zahara et al./Asian Pac J Trop Med 2014; 7(Suppl 1): S60-S69

parameters that need to be studied well. Biopesticides,


better-quality planting material produced through
micropropagation in combination with use of bio-fertilizers
(mycorrhiza) and improved agro-techniques would enhance
the yields even further and generate constantly higher
financial returns to the growers.
9.3. Post-harvest handling

The quality of medicinal plants also depends on the


manner of post-harvest handling. It is observed that during
harvesting, handling and storage, the collectors of herbal
material pay less consideration to quality of material. It
has been reported that stored herbal drug samples very
frequently harbour mycotoxin producing fungi.
Above the acceptable limit fixed by the World Health
Organization for human consumption, such herbal drugs
containing mycotoxins above would be rejected in the
global market. Therefore, efforts should be made in order to
encourage sustainable management of medicinal plants at
the community level itself by highlighting the improvement
of collection, cultivation and marketing practices.

10. Conclusion
S. lappa is a renowned medicinal plant that is often
prescribed in various indigenous systems of medicines
chiefly those of India, China, Tibet and Korea. It is used
for treatment of many ailments in allopathic and herbal
system 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 compounds
isolated from S. lappa are reported to have medicinal
properties. T he major components are sesquiterpene
lactones such as costunolide and dehydrocostus lactone. It
has various biological activities such as anticancer, antiinflammatory, hepatoprotective, anti-ulcer and cholagogic,
anticonvulsant, imunomodulator, gastroprotective,
angiogenesis, hypoglycaemic, spasmolytic, anti-hepatotoxic,
antidiarrheal, hypolipidaemic, antiparasitic, antimicrobial
and antiviral activity. It is also considered as an important
plant in terms of veterinary medicine and used against
the heart diseases of cattle. T he oil obtained from S.
lappa is very valuable and used in perfumery. The root is
considered as a reliable insect repellant as their smoke to
keep gnats, mosquitoes, and other flying insects at a space.
The preliminary experiments justify the reputation of the
drug as a useful remedy against cancer[26-29]. The results
of the different studies have empirically designated that
S. lappa is effectual as an anti-inflammatory agent. Total
methanol extract of S. lappa showed compelling inhibitory
effect on the formation of TNF-alpha, a pro-inflammatory
cytokine, in murine macrophage-like cell (RAW 264.7 cells).
The activity guided purification resulted in the isolation of
three sesquiterpene lactones, reynosin, cynaropicrin and
santamarine, which in a dose dependent manner inhibited
TNF -alpha production. I nflammation has been closely
related to rheumatism. Therefore, the anti-inflammatory
properties of S. lappa may be the reason for its ethnomedical
use in rheumatism. Some of the chemical constituents of S.

S67

lappa have been found to have the potential to be developed


as bioactive molecules. C ostunolide and cynaropicrin
have been identified as latent anticancer agents. Similarly,
cynaropicrin has been identified as the principal inhibitor
of TNF -alpha. D ehydrocostus lactone and costunolide
have been reported to display strong suppressive effect on
the expression of HBsAg in human hepatoma Hep3B cells
and therefore have the potential to be developed as antiHBV drugs. Although the published confirmation to date
supports 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 with
sufficient detail or assurance. Since S. lappa has various
medicinal applications, thats why more in vitro, clinical
and pathological studies are required to investigate the
unexploited potential of this plant.
As already mentioned, S. lappa has great demand in
pharmaceutical industry. So due to high demand, most
of the natural populations of the species are either have
been extirpated or are under destructive harvesting. It is
endemic to a geographically limited part of the Himalayas.
This critically endangered species is enlisted in Appendix
I of CITES. However, a multi-branched approach including
in situ and ex situ conservation and selection of betterquality genotypes followed by their multiplication could well
provide available solution to the problem.
Conflict of interest statement
We declare that we have no conflict of interest.
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