Review on Sphaeranthus indicus Linn. (Koṭṭaikkarantai)

Abstract

Sphaeranthus indicus Linn. is from the aroma family Asteraceae. It is also known with other synonyms such as Munditika, Mundi, Shravana, Bhikshu, Tapodhana, Mahashravani, Shravanahva, Shravanashirshaka. It is abundantly distributed in damp areas in plains and also as a weed in the rice fields. In the Indian system of medicine, the plant as a whole plant or its different anatomical parts viz., leaf, stem, bark, root, flower and seed are widely used for curing many diseases. The plant is bitter, stomachic, restorative, alterative, pectoral, demulcent and externally soothing. The whole plant and its anatomical parts have been reported with different types of secondary metabolites which include eudesmanolides, sesquiterpenoids, sesquiterpene lactones, sesquiterpene acids, flavone glycosides, flavonoid C-glycosides, isoflavone glycoside, sterols, sterol glycoside, alkaloid, peptide alkaloids, amino acids and sugars. The essential oils obtained from the flowers and whole plants were analyzed by different authors and reported the presence of many monoterpene hydrocarbons, oxygenated monoterpenes, sesquiterpene hydrocarbons and oxygenated sesquiterpenes. The whole plants, its isolated secondary metabolites and different anatomical parts have been reported for ovicidal, antifeedant, anthelmintic, antimicrobial, antiviral, macrofilaricidal, larvicidal, analgesic, antipyretic, hepatoprotective, antitussive, wound healing, bronchodilatory, mast cell stabilizing activity, anxiolytic, neuroleptic, immunomodulatory, anti-diabetic, antihyperlipidemic and antioxidant, antioxidant, central nervous system depressant, anti-arthritic, nephroprotective, anticonvulsant activities and many other activities. It is also effective on psoriasis. In the present paper, the plant is reviewed for its phytochemical and pharmacological reports in detail.

Full text

Pharmacognosy Reviews | July-December 2013 | Vol 7 | Issue 14 157
Review on Sphaeranthus indicus Linn. (Kot
.t
.aikkarantai)
Shakila Ramachandran
Department of Chemistry, Siddha Central Research Institute (Central Council for Research in Siddha), Anna Hospital Campus, Arumbakkam,
Chennai, Tamil Nadu, India
Submitted: 01-05-2013 Revised: 10-05-2013 Published: **-**-****
Address for correspondence:
Mrs. R. Shakila, Siddha Central Research Institute (Central
Council for Research in Siddha), Anna Hospital Campus,
Arumbakkam, Chennai - 600 106, Tamil Nadu, India.
E-mail: shakilasiva@gmail.com
Sphaeranthus indicus Linn. is from the aroma family Asteraceae. It is also known with other synonyms such as Munditika,
Mundi, Shravana, Bhikshu, Tapodhana, Mahashravani, Shravanahva, Shravanashirshaka. It is abundantly distributed in
damp areas in plains and also as a weed in the rice elds. In the Indian system of medicine, the plant as a whole plant or its
different anatomical parts viz., leaf, stem, bark, root, ower and seed are widely used for curing many diseases. The plant
is bitter, stomachic, restorative, alterative, pectoral, demulcent and externally soothing. The whole plant and its anatomical
parts have been reported with different types of secondary metabolites which include eudesmanolides, sesquiterpenoids,
sesquiterpene lactones, sesquiterpene acids, avone glycosides, avonoid C‑glycosides, isoavone glycoside, sterols, sterol
glycoside, alkaloid, peptide alkaloids, amino acids and sugars. The essential oils obtained from the owers and whole plants
were analyzed by different authors and reported the presence of many monoterpene hydrocarbons, oxygenated monoterpenes,
sesquiterpene hydrocarbons and oxygenated sesquiterpenes. The whole plants, its isolated secondary metabolites and
different anatomical parts have been reported for ovicidal, antifeedant, anthelmintic, antimicrobial, antiviral, macrolaricidal,
larvicidal, analgesic, antipyretic, hepatoprotective, antitussive, wound healing, bronchodilatory, mast cell stabilizing activity,
anxiolytic, neuroleptic, immunomodulatory, anti-diabetic, antihyperlipidemic and antioxidant, antioxidant, central nervous
system depressant, anti-arthritic, nephroprotective, anticonvulsant activities and many other activities. It is also effective
on psoriasis. In the present paper, the plant is reviewed for its phytochemical and pharmacological reports in detail.
Key words: 5,4’‑Dimethoxy‑3’‑prenylbiochanin‑7‑O‑β-D-galactoside, 7-hydroxy eudesmanolide, Kot
·t
·aikkarantai, Munditika
churna, Veezhi Ennai
INTRODUCTION
Sphaeranthus indicus Linn. is known as Kot
.
t
. aikkarantai
in Tamil. It is a multi-branched aromatic herb 1-2 feet in
height, distributed widely in plains all over India and up to
an altitude of 50 feet in hills. It is an important medicinal
plant used for the treatment of styptic gastric disorders,
skin diseases, anthelmintic, glandular swelling, nervous
depression, analgesic, antibiotics, antifungal, laxative and
diuretic properties. The decoction of the plant is said to be
active against bronchitis, asthma, leucoderma, jaundice and
scabies. The powdered bark along with whey is useful in
the treatment of piles. Flowers have alterative, depurative
and stimulant characters. Roots and seeds are anthelmintic.
Juice of fresh leaves is taken for cough. The plant is also
useful in preservation of food grains as it possess insecticidal
property.[1-6] Earlier, the plant has been reviewed by some
authors.[7-10] However, in the present paper author aims to
describe the plant on Siddha as well as Ayurvedic aspects,
phytochemical and pharmacological aspects.
REGIONAL NAMES
S. indicus Linn. is known in different names in different
Indian languages as mentioned below:[11]
• Sanskrit:Mundi,Śrāvani Kadamba, Pus
.pikā,
Alambusta
• Assamese: Kamadarus
• Bengalese: Surmuriya, Chhagal Nadi, Mudmudiya
• Gujarati: Gorakhmundi
• Hindi: Mundi
• Kannada: Mirnagnee, Atookamanni, Mirangnee
• Marathi: Mundi, Baras Bondi
• Oriya: Buikadam
• Punjabi: Gorakhmundi
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ABSTRACT
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Ramachandran: Review on Sphaeranthus indicus Linn
158 Pharmacognosy Reviews | July-December 2013 | Vol 7 | Issue 14
• Tamil: Kotook, Karandai, Kottakarthai
• Telelugu: Bodasaramu, Bodataramu
• Urdu: Mundi.
SIDDHA PROPERTIES
S. indicus Linn. is used in Siddha system of medicine in the
name of Kot.t.aikkarantai. Other properties as described in
this system are listed below. It is used as one of the ingredient
in the siddha preparation, “Veezhi Ennai (or Veezhi oil).”[12]
Though this plant finds place in many preparations, this is
the only preparation mentioned in the official publication.
• Suvai (Taste): Kaippu (Bitter)
• Tanmai (Potency): Veppam (Hot)
• Gunam: Ilaku (Soft)
• Pirivu(Transformation):Kārppu(Pungent)
• Ceikai(Action):Uļļalalārri(Demulcent),Ut
.arterri
(Restorative), Puzhukkolli (Anthelmintic),
Uramaakki (Tonic).
AYURVEDIC PROPERTIES
• Rasa: Madhura, Kat
.u,Tikta,Kasāya
• Guna: Laghu
• Virya: Usna
• Vipaka: Kat
.u
• Karma: Medhya, Vit
.aghna,Vātakaphahara,
Arśadosa,Vināśaka.[11]
IMPORTANT AYURVEDIC FORMULATIONS
Navaratnarāja,Mt
.gānkaRasa,ArkaMut
.t
.ī,Guduchyadi
taila, Vatagajankusha rasa, Munditika churna, Guduchi
taila.[11]
AYURVEDIC THERAPEUTIC USES
Gant.amālā,Apaci,Kut.t.ha, Kt.mi,Pāt.t.u, Slipada,
Medaroga, Apasmara, Kasa, Mutrakrcchra, Tvaka Roga,
StanaSaithalya,Yonirogā,Āmātisara,Āmaroga,Vātaroga,
Gudaroga,Plīhāroga,Chardi,Āmavāta,Gātradurgandhya,
Sūryāvarta,Ardhāvabhāvabhedaka.[11]
DOSE
3-6 g of the drug.[11]
PHARMACOGNOSTIC STUDY
The physico-chemical parameters and estimation of
7-hydroxy eudesmanolide (1), a major sesquiterpene lactone
had been carried out
. S. indicus was described as a branched,
hairy and strongly scented herb; leaves spathulate, sessile;
flowers pinkish purple. Leaf shows uni-multicellular
and club and clavate type of trichomes. Ring of deltoid
vascular bundles and well-developed pith with few pitted
cells are found in stem. Metaderm and radially arranged
fibers are seen in root; in the cortical region secretory canal
are alternatively arranged. Powder shows large number
of different types of trichomes, pollen grains in pollen
sacs and cruciferous stomata. 7-hydroxy eudesmanolide
was quantified (0.0658% w/w) by high performance thin
layer chromatography method using the solvent system of
n-hexane: diethyl ether (3:7) at λ 213 nm.[13]
PHYTOCHEMICAL STUDIES
Spaeranthine, an alkaloid of molecular formula C13H19O5
(m.p. 166-168°C) was isolated from the plant
. The essential
oil from the fresh flowering plant was isolated and it was
characterized for physical and chemical properties viz.,
specific gravity at 30° (0.9419 68), refractive index at
20° (1.512), optical rotation (nil), acid value (2.4030), ester
value (47.80), ester value after acetylation (74.15).[14]
The essential oil from the plant was reported to contain
methyl chavicol (12), δ-cadinene (11), α-ionone (2),
para-methoxycinnamaldehyde (4), α-terpinene (9), citral (6),
geraniol (7), geranyl acetate (8), β-ionone (3), oscimene
(10), eugenol (5), sphaeranthene, sphaeranthol, estragole,
indicusene.[15,16]
β-Sitosterol, n-triacontanol, phenylurethane, n-pentacosane
were isolated from oil.[17] The alcoholic extract yielded
sterols, viz., stigmasterol (13) and β-sitosterol (14).[18]
Phytochemical analysis of S. indicus yielded three interesting
hydroxy lactones (15-17).[19]
A bicyclic sesquiterpene lactone (18) was isolated from the
petroleum ether extract of the aerial part.[20]
A new sesquiterpene lactone, 7α-hydroxyeudesm-4-en-6,
12-olide (19) and a new sesquiterpene acid, 2-hydroxycostic
acid (20), along with the known compounds β-eudesmol (21)
and ilicic acid (22) have been isolated from the acetone extract
of S. indicus L.[21]
A sterol glycoside has been isolated and characterized
as β-D-glucoside of (24S)-24-ethylcholesta-4,22-dien-3-
β-ol (23).[22] 7-Hydroxyfrullanolide (7HF) (24), was reported
from S. indicus Linn.[23] A new sesquiterpene glycoside,
sphaeranthanolide (25), has been isolated from the flowers
of S. indicus.[24]

Ramachandran: Review on Sphaeranthus indicus Linn
Pharmacognosy Reviews | July-December 2013 | Vol 7 | Issue 14 159
Three new eudesmanolides, 11α,13-dihydro-3α,7α-dihydr
oxyfrullanolide (26), 11α,13-dihydro-7α,13-dihydroxyfrul
lanolide (27) and 11α,13-dihydro-7α-hydroxy-13-methoxy
frullanolide (28) were isolated from the flowers of S. indicus.
Their structures were determined by 2D nuclear magnetic
resonance and other spectroscopic techniques.[25]
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Ramachandran: Review on Sphaeranthus indicus Linn
160 Pharmacognosy Reviews | July-December 2013 | Vol 7 | Issue 14
Two Sphaeranthus peptide alkaloids (1 and 2) (29,30) have
been isolated from flowers.[26]
Two new eudesmanolides (31 and 32) along with 7α-hydr
oxyeudesm-4-en-6,12-olide (33) and two sesquiterpenoids,
cryptomeridiol (34) and 4-epicryptomeridiol (35) have been
isolated from S. indicus.[27]
A new 5α,7-dihydroxyeudesmanolide (36) along with two
known eudesmanolides (31,32) have been obtained from the
photo-oxidation of a known 7-hydroxyeudesmanolide.[28]
Amino acids, viz., glycine, alanine, valine, leucine, histidine,
cysteine, lysine, aspartic acid and glutamic acids and sugars
viz., D-arabinose, L-rhamnose, lactose, raffinose, D-galactose,
maltose, D-fructose and D-glucose were reported the
chemical examination of the leaves of S. indicus.[29]
Anewflavoneglycoside,7‑hydroxy‑3′,4′,5,6‑tetramethoxy
flavone 7-O-β-D-diglucoside (37) was isolated from the stem.[30]
A novel isoflavone glycoside, 5,4’-dimethoxy-3’-prenylbiochanin
7-O-β-D-galactoside (38), was isolated from the leaves of
S. indicus.[31]
Three new eudesmanoids have been isolated from whole
plant and their structures were established as 11α,13-dihydr
o-3α,7α-dihydroxy-4,5-epoxy-6β,7-eudesmanolide (39), 11α,
13-dihydro-7α-acetoxy-3β-hydroxy-6β,7-eudesm-4-enolide
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Ramachandran: Review on Sphaeranthus indicus Linn
Pharmacognosy Reviews | July-December 2013 | Vol 7 | Issue 14 161
(40) and 3-keto-β-eudesmol (41) by comparison of spectral
data with those of other 7α-hydroxyeudesmanolides.[32]
The hydro distilled essential oil of S. indicus was
analyzed by gas chromatography (GC) and GC/mass
spectrometry. Thirty-eight compounds making up 84.0%
of the oil were identified. The major compounds were:
2,5-dimethoxy-ρ-cymene (18.2%), α-agarofuran (11.8%) (46),
10-epi-γ-eudesmol (7.9%) and selin-11-en-4α-ol (12.7%). Other
detected compounds were (Z)-3-hexenol, (E)-2-hexenol,
α-pinene, camphene (42), 6-methyl 5-hepten-2-one,
β-pinene (43), myrcene (44), α-phellandrene (45), ρ-cymene,
limonene (47), α-ρ-dimethylstyrene, linalool, camphor (56),
borneol (52), terpinen-4-ol, nerol, neral, geraniol, geranial,
maaliene, β-cubebene, β-elemene (53), β-caryophyllene,
2,5-dimethoxy-1-isopropenyl-4-isopropylbenzene,
α-humulene, dihydroagarofuran (54), indipone (52),
caryophyllene oxide (55), globulol, cis-arteannuic alcohol,
guaiol (51), trans-arteannuic alcohol, cubenol (49),
α-muurolol, α-eudesmol and valianol.[33]
A novel flavonoid C-glycoside, 5-hydroxy-7-methoxy-
6-C-glycosylflavone (57), was isolated from the aerial part.
Its structure was elucidated by spectroscopic methods.[34]
Two new eudesmanolides have been isolated[35] from the
aerial part and their structures have been established as
11α,13-dihydro-3α,7α-dihydroxyeudesm-4-en-6α,12-oli
de, 4-en-6β,7α-eudesmanolide, based on the spectral data
and in comparison of spectral data with those of reported
data of 11α,13-dihydro-3α,7α-dihydroxyfrullanolide,[25]
eudesmanolide-4[19] and γ-cyclocostunolide.[36]
PHARMACOLOGICAL STUDIES
Ovicidal activity
Sesquiterpene lactone, isolated from a petroleum ether
extract of S. indicus, was screened for its effects on the
hatching of eggs and the metamorphosis of larvae of
Culex quinquefasciatus at concentration of 50-250 ppm.
Rates of fecundity and fertility were found to be affected
in the larval-treated adult females. Egg hatching was also
significantly lowered. Mortality in the larvae, pupae and
adults produced a marked decrease in mosquito populations
in laboratory experiments.[37]
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Ramachandran: Review on Sphaeranthus indicus Linn
162 Pharmacognosy Reviews | July-December 2013 | Vol 7 | Issue 14
Hepatoprotective activity
The protective effectof methanolic extract of S. indicus
Linn. (MES) against CCl4 induced hepatotoxicity was studied
in animal models. It showed a significant protective effect
by lowering the serum aspartate aminotransferase, alanine
aminotransferase and alkaline phosphatase (ALP).[38]
The aqueous (AQS) and methanolic (MES) extracts of flower
head of S. indicus L. were evaluated for the hepatoprotective
and antioxidant effect on acetaminophen (APAP)-induced
heptotoxicity in rats. Oral dose of MES (300 mg/kg)
showed a significant hepatoprotective effect (serum glutamic
oxaloacetic transaminase (SGOT), serum glutamic pyruvic
transaminase (SGPT), acid phosphatase (ACP) and ALPthan
aqueous extract. MES exhibited significant antioxidant activity
showing increasing levels of superoxide dismutase (SOD),
catalase (CAT) and glutathione peroxidase (GPX) by
reducing malondialdehyde levels.[39]
Ethanolic extract in the doses 200 and 300 mg/kg bw, of aerial
parts of S. indicus L. was investigated for hepatoprotective
activity against paracetamol induced liver damage of rat.
300 mg/kg of extract showed significant protection against
paracetamol-induced hepatocellular injury.[40]
Aqueous extract (200 and 300 mg/kg b/w) of root of S.
indicus L. was evaluated for hepatoprotective activity
against APAP induced hepatotoxicity in rats. The activity of
300 mg/kg of the extract was comparable to standard drug,
silymarin (50 mg/kg body weight).[41]
Antitussive activity
The successive methanol extract of S. indicus (MESI) exhibited
antitussive activity and synergistic effects of sleeping time
induced by standard sedatives using Swiss Albino mice.
The MESI of (200, 300 and 400 mg/kg) showed maximum
inhibition of cough by 71.24%, 76.84% and 77.92% and also
exhibited significant synergistic effect (P < 0.001) at the
dose levels of 200, 250 and 300 mg/kg when compared with
control and standard sedative pentobarbitone and diazepam.
The MESI produced significant synergistic effects three times
greater than that of standard sedatives.[42]
Wound healing activity
A cream containing ethanolic extract of aerial parts of S.
indicus, L. (Asteraceae) was evaluated for wound healing
activity in guinea pigs. The cream was applied in‑vivo on
the paravertebral area of six excised wounded models once
a day for 15 days. The cream significantly enhanced the rate
of wound contraction and the period of epithelialization
comparable to neomycin.[43]
The wound healing activity of ointments comprising various
percentage of alcoholic extract of S. indicus flower head was
tested for protection against microbial invasion by providing
better tissue formation. The formulation comprising of
2% (w/w) alcoholic extract was found to be superior to
control and standard formulation.[44]
A randomized placebo controlled single blind study was
conducted on 45 patients (n = 30 test and n = 15 control
groups) to test the efficacy and safety of S. indicus L., cream
of Lawsonia inermis L. and Plumbi oxidum. The test drug
formulations were found to be effective in healing and
relieving the symptoms of cervical erosion with cervicitis.[45]
Anxiolytic activity
The petroleum ether (10 mg/kg), alcohol (10 mg/kg) and
water extracts (30 mg/kg) of flowers were tested to assess
the anxiolytic activity in mice. Petroleum ether extract of
S. indicus flowers produced prominent anxiolytic activity.[46]
Neuroleptic activity
Neuroleptic activity of extract of flowers was evaluated
in apomorphine induced cage climbing and catalepsy in
mice models. The petroleum ether extract (300 mg/kg,
i.p.) reduced total time spent in apomorphine induced cage
climbing. Aqueous and alcoholic extracts showed catalepsy
while petroleum ether extract was devoid of it.[47]
Immunomodulatory activity
Immunostimulant activity of sphaeranthanolide was tested
by Jerne plaque assay method. This compound was found
to be an immune modulator.[24]
Methanol extract, its petroleum ether, chloroform and
remaining methanol fractions, of flower heads were found
effective in increasing phagocytic activity, hemagglutination
antibody titer and delayed type hypersensitivity, whereas
only remaining methanol fraction was found active
in normalizing total white blood celllevels in case of
cyclophosphamide induced myelosuppression in mice.
The study, therefore, revealed that the drug holds promise
as immunomodulatory agent, which acts by stimulating
both humoral as well as cellular immunity and phagocytic
function.[48]
The bioactive fraction exhibited dose dependent increase in
immoral and cell-mediated immunity and offers protection
against immunosuppression induced by the cytotoxic agent
cyclophosphamide.[49]
The petroleum ether extract from the flower heads of
S. indicus Linn. was found to be effective in increasing
phagocytic activity, hemagglutination antibody titer and
delayed type hypersensitivity. The extract acts by stimulating
both humoral and cellular immunity as well as phagocytic
function.[50]
Antifeedant activity
MESI showed antifeedant activity against 4th instar larvae of
Spodoptera litura. Among the compounds isolated from this

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Pharmacognosy Reviews | July-December 2013 | Vol 7 | Issue 14 163
fraction, 7-hydroxy frullanolide had high antifeedant activity
at 1,000-ppm. Deformities in larvae, pupae and adult were
also observed.[51]
Anthelmintic activity
The anthelmintic activities of ethanolic and aqueous extracts
(10, 50, 100 mg/ml concentration levels) of the whole
plant were tested against Pheretima posthuma and Ascardia
galli. Both extracts exhibited anthelmintic activity in a
dose-dependent manner. The most significant activity was
observed at the highest concentration of 100 mg/ml against
both types of worms.[52]
Analgesic Activity
The ethanol extracts of the whole plant S. indicus Linn.
exhibited dose dependent analgesic activity with 66.6 and
67.4% of protection when tested with 250 mg and 500 mg/
kg b.w. by tail immersion method in rat models using
pentazocine 10 mg/kg as standard.[53]
Analgesic and antipyretic activity
The analgesic and antipyretic activity of the successive taking
petroleum ether, benzene, chloroform, ethanol and triple
distilled water extracts (200 mg/kg and 400 mg/kg b.w)
of whole plant was screened for analgesic and antipyretic
activities on Albino rats by Eddy’s hot plate, Tail immersion
and Brewer’s yeast induced pyrexia method. The petroleum
ether, chloroform and ethanol extracts showed significant
analgesic activity in both doses as compared to the standard
drug diclofenac sodium. The chloroform and ethanol extracts
showed potential significant antipyretic activity from 1 h
onward whereas aqueous extracts exhibited activity from
2 h onward as compared to the standard drug paracetamol
amongst various extracts.[54]
Anti‑diabetic activity
The anti-hyperglycemic effect of S. indicus extract was carried
out in diabetic rats induced by nicotinamide (120 mg/kg i.p.)
and streptozotocin (STZ) (60 mg/kg i.p). Oral administration of
alcoholic extract of S. indicus for 15 days exhibited in significant
reduction in blood glucose levels and increases in hepatic
glycogen and plasma insulin levels and significant improvement
in oral glucose tolerance test. Glibenclamide was used as a
reference standard.[55]
The ethanol extract of aerial part was evaluated for anti-diabetic
activity using the glucose uptake by isolated rat hemi-diaphragm
in-vitro model. S. indicus increased the uptake of glucose by
isolated rat hemi-diaphragm significantly (P < 0.01) and was
found to be more effective than insulin and it will be alternative
choice for the treatment of diabetes mellitus caused in the
consequences of resistance to stimulatory effect of insulin on
glucose transporter type 4 protein.[56]
The effect of the methanol extract in dexamethasone-induced
insulin resistance in mice was studied. The mice were treated
with dexamethasone for 22 days. The S. indicus extract
showed significant decrease in plasma glucose and serum
triglyceride levels at doses, of 400 and 800 mg/kg, p.o. and
stimulated insulin assisted and non-insulin assisted glucose
uptake in skeletal muscle. The extract significantly restored
dexamethasone induced body weight loss thereby suggesting
its effect in the treatment of type II diabetes mellitus.[57]
Dried petroleum ether (60-80°C) extract of flower head of
S. indicus was screened for activity against alloxan induced
hypoglycemea in Wistar rats. The oral administration of
flower head extract at doses of 200 mg/kg lead to a significant
blood glucose reduction.[58]
The anti-diabetic effect of MES in alloxan induced diabetic
rabbits in comparison with 80 mg/kg of diamicron
standard was studied. The extract at the dose of 300 mg/
kg body weight significantly reduced the blood glucose
level, plasma total cholesterol, triglycerides and low density
lipoprotein (LDL) in treated rabbits as compared to diabetic
rabbits; also significantly increased the level of high density
lipoprotein (HDL) (36.95 ± 2.95); SGOT and SGPT also
significantly decreased.[59]
Anti‑diabetic, antihyperlipidemic and antioxidant
The anti-diabetic, antihyperlipidemic and in‑vivo antioxidant
properties of the root in STZ-induced type 1 diabetic rats
was studied. The ethanolic extract 100 and 200 mg/kg to the
diabetic rats showed significant reduction in blood glucose
and increase in body weight compared with diabetic control
rats. Both doses showed significant alteration in elevated
lipid profile levels, significant increase in SOD, CAT, GPX
and decrease in thiobarbituric acid reactive substances levels
than diabetic control rats. 200 mg/kg produced significant
higher antioxidant activity than 100 mg/kg. These activities
are possibly due to the presence of biomarkers gallic
acid and quercetin revealed by high performance liquid
chromatography analysis of the extract.[60]
Antimicrobial activity
The bicyclic sesquiterpene lactone isolated from the
petroleum ether extract of the aerial part has been found
to be potent against Staphylococcus aureus, Escherichia
coli, Fusarium sp., Helminthosporium sp., and other
microorganisms.[20] 7HF, a sesquiterpene lactone showed
antimicrobial activity.[23] Alcoholic and aquous extracts of the
plant were highly effective against Alternaria solani, Fusarium
oxysporum and Penicillium pinophilum by preventing their
growth to a greater extent.[61] Antimicrobial activity of
terphenoidal compound isolated from S. indicus showed
activity against Bacillus subtilis.[62] The in‑vitro antimicrobial
activity of aqueous extract of flower was evaluated against
coliforms E. coli (10,536) and total coliforms by using disc
diffusion method. The extracts showed significant inhibition
against coliform strains.[63]

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164 Pharmacognosy Reviews | July-December 2013 | Vol 7 | Issue 14
Leaves, flower stem and roots were extracted separately with
methanol, ethanol, chloroform, petroleum ether and hot
water and the extracts were screened for its phytochemical
constituents. The plant revealed the presence of alkaloids,
saponins, tannins, flavonoids, steroids, terpenoids, cardiac
glycosides, amino acids, mono saccharides and reducing sugar.
Leaves extracts showed significant amount of phytochemicals
and hence antimicrobial studies of leaves extracts were carried
out against bacterial species such as Bacillus sp. Staphylococcus
sp., Klebsiella sp., E. coli, Pseudomonas sp., using filter paper
and agar well diffusion method at 4 different concentrations.
MES and AQS of leaf showed the highest inhibitory effect
compared to all other extracts and it showed good inhibitory
activity against Bacillus sp., followed by Staphylococcus sp.
The gram-positive bacteria were found to be more susceptible
than gram-negative bacteria. Antifungal activity of methanol
and ethanol extracts were tested against Penicillum sp., and
Aspergillus sp. and the growth was found to decreasewith
increase in concentration of the extracts.[64,65]
Hexane, benzene, chloroform, ethyl acetate and acetone
extracts of the aerial parts and flowers showed activity against
B. subtilis, S. aureus and Staphylococcus epidermidis. Benzene
and chloroform extracts of flower and benzene and acetone
extracts of aerial parts were not active against Enterococcus
faecalis; all extracts of flower and aerial part were not active
against E. coli and Klebsiella pneumonia when tested by disc
diffusion method.[66]
Four new alkaloids have been isolated from the alcoholic
extract of flowers. The crude extract showed antibacterial
activity against 18 different gram-positive and gram-negative
bacteria. Both alkaloidal and non-alkaloidal fractions showed
the activity. The isolated two alkaloids showed broad
spectrum activity.[67]
Ten Indian medicinal plants were screened for antibacterial
activity specific to enteropathogens. Diffusion and dilution
methods were used to measure the antibacterial activity.
Allium sativum, Camellia sinensis and Chamaesyce hirta
showed higher activity when compared to the rest. They
had a minimum bactericidal concentration of <100 μg/ml
and gave inhibition zones of more than 2 cm. Among the
pathogens studied, Vibrio cholerae and Shigella flexneri were
found to be highly susceptible to the plant extracts.[68] The
essential oil from the leaves exhibited antibacterial activity
against Salmonella paratyphi A, B and C, S. flexner, Salmonella
enteritidis, Salmonella typhimurium, Shigella sonnei and Vibrio
cholera.[69] The fruits showed very good antibacterial activity
against gram-positive and gram-negative bacteria.[70] The plant
also exhibited antifungal activity.[71] The petroleum ether,
acetone, methanol (90%) and aqueous extracts of flowers
also exhibited remarkable antibacterial and strong antifungal
activities.[72]
The hexane, chloroform, ethyl acetate, ethanol, methanol
and aqueous extract of entire part including flower heads
exhibited antimicrobial activity compared with gentamycin
and nystatin as standards. The chloroform, methanol and
aqueous extracts showed high antibacterial activity against
S. aureus; chloroform, methanol and ethanol extract against
P. aeroginosa, methanol, chloroform and hexane against
B. substilus, aqueous, methanol, ethyl acetate and chloroform
against E. coli.[73]
Antiviral activity
The methanol extract was found to exhibit inhibitory
activity against Mouse corona virus and Herpes simplex virus
at a concentration of 0.4 μg/ml.[74] The plant also showed
antiviral activity against vaccinia and ranikhet viruses.[75]
Macrolaricidal activity
The methanolic extract showed macrofilaricidal activity
(4 mg/ml) against adult Setaria digitata, the cattle filarial
worm when tested by worm motility assay method.[76]
Larvicidal action
Acetone extract of root and leaf caused >50% mortality in
an Indian mosquito specie, which acts as a vector of filarial
worm. Root extract was more active than leaf extract.[77]
Purified fraction of acetone extract showed mosquito larvicidal
effect. Methanolic extract showed repellent and feeding
deterrent activities against Tribolium castaneum in the lower
concentration of 1%; complete feeding deterrent activity at
5 ml and repellent activity at 4 ml dose.[78]
Antioxidant activity
The free radical scavenging potential of the plant
was studied by using different antioxidant models
of screening. The ethanolic extract at 1,000 μg/ml
showed maximum scavenging of the radical cation,
2,2-azinobis-(3-ethylbenzothiazoline-6-sulphonate) observed
up to 41.99% followed by the scavenging of the stable radical
1,1-diphenyl, 2-picryl hydrazyl (33.27%), SOD (25.14%)
and nitric oxide radical (22.36%) at the same concentration.
However, the extract showed only moderate scavenging
activity of iron chelation (14.2%). Total antioxidant capacity
of the extract was found to be 160.85 nmol/g ascorbic
acid. The results justify the therapeutic applications of the
plant in the indigenous system of medicine, augmenting its
therapeutic value.[79]
Attenuation effect on prostatic hypertrophy
The attenuating effect of petroleum ether, ethanolic, aqueous
extracts and β-sitosterol on prostatic hyperplasia induced
by testosterone in Albino rats. Finasteride was used as a
positive control (1 mg/kg p.o.). The petroleum ether extract
exhibited the best activity, although the ethanol and aqueous
extracts also exhibited significant activity thereby indicating
the potential use of S. indicus in the treatment of prostatic
hyperplasia.[80]

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Anxiolytic, central nervous system depressant and
anticonvulsant activities
The hydroalcoholic extract in the doses of 100, 200,
500 mg/kg, p.o. was experimented on induced anxiety,
depression and convulsions in rodents; anticonvulsant
effect on pentylenetetrazole-induced convulsions in mice;
and maximal electroshock-induced convulsions in rats. S.
indicus demonstrated anxiolytic, central nervous depressant
and anticonvulsant activities in rodents; thus, supporting
the folk medicinal use of this plant in nervous disorders.[81]
Effect on psoriasis
The effect of S. indicus on psoriasis was studied and found
to exhibit the potent activity.[82]
Bronchodilatory effect
The methanolic extract and its fractions viz. petroleum ether,
benzene, chloroform and ethyl acetate exhibited significant
protection against bronchospasm, induced by histamine in
guinea pigs. Significant protection exhibited by methanolic
extract was comparable with the standard chlorophenarmine
maleate (2 mg/kg).[83]
Mast cell stabilizing activity
The protective effect of different extracts of whole plant
against the compound 48/80 and sheep serum induced mast
cell degranulation was evaluated. The ethanol extract at the
dose levels of 150 mg/kg and 300 mg/kg and ethyl acetate
extract at the dose levels of 100 mg/kg, 150 mg/kg and
300 mg/kg showed slightly better protection of mast cell
degranulation (77-86%) than ketotifen (75%) in the sheep
serum model. These extracts also showed better mast cell
stabilizing activity (77-88%) than the standard drug (69%)
when peritoneal mast cells are treated with compound
48/80. These results suggest that S. indicus has potent mast
cell stabilizing effects thereby inhibiting mediator release
from mast cells.[84]
Antihyperlipidemic activity
The alcoholic extract of flower heads in atherogenic diet
induced hyperlipidemia in rats was investigated for the dose
of 500 mg/kg/day, p.o. for 8 days. The extract effectively
suppressed the hyperlipidemia by decreasing total cholesterol,
triglyceride, LDL and very low density lipoprotein (VLDL);
increasing the HDL.[85]
Anti‑arthritic activity
The anti-arthritic activity of the petroleum ether extract of
the flowers in the doses 10, 30 and 100 mg/kg/day p.o. was
investigated against complete Freund’s adjuvant induced
arthritis in laboratory rats. Indomethacin (2 mg/kg/day
p.o.) was the standard drug. The dose of 100 mg/kg/day p.o.
showed significant anti-arthritic activity.[86]
Anti‑inammatory activity
The anti-inflammatory effect of ethanolic extract was
evaluated. The extract in different doses (100, 200 and
400 mg/kg, p.o.) exhibited dose dependent and significant
anti-inflammatory activity in acute (carrageenan induced
hind paw edema, P < 0.05) and chronic (cotton pellet
granuloma formation, P < 0.05) model of inflammation.[87]
Anti‑inammatory and analgesic activity
The anti-inflammatory and analgesic activities of ethanolic
extract of S. indicus flowers in doses of 300 and 500 mg/
kg was tested on Albino mice and rat of either sex.
Anti-inflammatory activity was evaluated by measuring
the mean decrease in hind paw volume after the sub planter
injection of carrageenan. The analgesic activity was tested
against acetic acid induced writhing response using Albino
rats. At the end of 1 h, the inhibition of paw edema was
42.66 and 50.5% respectively and the % of protection from
writhing was 62.79 and 68.21 respectively.[88]
Anti‑inammatory, anti‑migratory and anti‑proliferative
activity
Chronic inflammation induced hyper-proliferation and
migration of keratinocytes are pathological hallmarks of
psoriasis. Extracts from Sphaeranthus spp. demonstrate
pharmacological activity in‑vitro and in‑vivo. However, the
activity in modulating disease relevant pathways in psoriasis
has not been reported. In the current study a standardized
herbal extract from S. indicus (NPS31807) was used to study
the mechanistic activity under conditions of inflammation,
keratinocyte proliferation and migration using cell based and
gene expression assays. NPS31807 treatment reduced levels
of pro-inflammatory cytokines from human macrophages
and activated epidermal keratinocytes in a dose dependent
manner. Treatment with NPS31807 diminished NFκB and
AP-1 transcription activity in human macrophages. Lowered
nuclear translocation of p65 sub-unit in macrophages by
treatment confirmed reduced activity of NFκB. Gene
expression profiling showed attenuated expression of
genes involved with inflammation such as tumor necrosis
factor (TNF) signaling and angiogenesis by NPS31807.
Inhibition of angiogenesis and matrix metalloproteinase
production in keratinocytes was confirmed using real-time
quantitative-polymerase chain reaction assays. Pretreatment
with NPS31807 led to significant reduction of signal
transducer and activator of transcription 3 phosphorylation
and mitogen induced cellular migration. NPS31807 induced
inhibition of proliferative genes and BrdU uptake in
epidermal keratinocytes. In summary, our study provides
novel molecular insights into the anti-inflammatory,
anti-migratory and anti-proliferative properties of NPS31807.
In summary, NPS31807, an extract from S. indicus can be
used as therapeutic option in inflammatory and auto-immune
conditions such as psoriasis.[89]
The anti-inflammatory effect S. indicus was found to be
potent in suppressing the proinflammatory cytokines
interleukin-8 (IL-8) and TNF-α induced by the culture

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166 Pharmacognosy Reviews | July-December 2013 | Vol 7 | Issue 14
supernatant of Propionibacterium acnes in polymorphonuclear
leukocytes and monocytes than that of other tested plants,
viz., Rubia cordifolia, Curcuma longa, Hemidesmus indicus
and Azadirachta indica.[90]
7HF significantly reduced the production (induced/
spontaneous) of TNF-α and IL-6 from freshly isolated
human mononuclear cells, synovial tissue cells isolated
from patients with active rheumatoid arthritis and BALB/c
mice. Oral administration of 7HF significantly protected
C57BL/6J mice against endotoxin-mediated lethality.
In the dextran sulfate sodium (DSS) model of murine
colitis, oral administration of 7HF prevented DSS-induced
weight loss, attenuated rectal bleeding, improved disease
activity index and diminished shortening of the colon of
C57BL/6J mice. Histological analyses of colonic tissues
revealed that 7HF attenuated DSS-induced colonic edema,
leukocyte infiltration in the colonic mucosa and afforded
significant protection against DSS-induced crypt damage.
7HF was also significantly efficacious in attenuating
carrageenan-induced paw edema in Wistar rats after oral
administration. In the collagen-induced arthritis in DBA/1J
mice, 7HF significantly reduced disease associated increases
in articular index and paw thickness, protected against
bone erosion and joint space narrowing and prominently
diminished joint destruction, hyperproliferative pannus
formation and infiltration of inflammatory cells. These
results provide evidence that 7HF-mediated inhibition of
pro-inflammatory cytokines functionally results in marked
protection in experimental models of acute and chronic
inflammation.[91]
Hypolipidemic activity
The effect of AQS (300 mg/kg/day, i.p) against dexamethasone
(10 mg/kg/day, s.c) induced changes in lipid profile was
studied in rat. S. indicus decreased the serum total cholesterol,
triglyceride, LDL and VLDL significantly but not HDL; it
also reduced atherogenic index significantly thus indicating
its lipid lowering effect.[92]
Nephroprotective effect
The ethanolic extract was screened for nephroprotectivity
in gentamicin induced acute renal injury in rats. The extract
in the dose of 300 mg/kg was found to increase blood urea,
serum creatinine and decrease the total protein and serum
albumin of the treated group compared to normal group.[93]
Other activities
The plant was also found to exhibit anticancer activity
and antiprotozoal activity against Entamoeba histolytica.[75]
The alcoholic extract of the flower exhibited hypotensive,
peripheral vasodilatory and cathartic activities.[94] The extract
of the plant was found to inhibit hyaluronidase.[95] The extract
effected toxicity on second and fourth instar larvae of Calex
quinquefasciator mosquito at 100-500 ppm concentration.[96]
The methanolic extract of dried fruit exhibited nematocidal
activity.[97] The methanolic extract (<4 mg/mL) showed
macrofilaricidal activity within an incubation period of
100 min by the worm motility assay against adult S. digitata,
a cattle filarial worm.[78]
CONCLUSION
From the literature survey it is evident that S. indicus Linn.
has been exhaustively worked out for both chemical and
pharmacological studies. In all the reported pharmacological
activities, it is found to be more potent. It finds a broad
spectrum of therapeutic usage. As the plant is widely
distributed, it could be considered for new drug formulations.
ACKNOWLEDGMENT
Author is thankful to Dr. M. Padma Sorna Subramanian,
Research Officer (Botany), SMPG, Mettur for plant photograph,
Shri. D. Radhakrishna Reddy for technical help and Research
Officer (S) I/c, SCRI for encouragement.
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Pharmacognosy Reviews | July-December 2013 | Vol 7 | Issue 14 169
How to cite this Article: Ramachandran S. Review on
Sphaeranthus indicus
Linn. (Kot
.
t.aikkarantai). Phcog Rev
2013;7:157-69.
Source of Support: Nil, Conict of Interest: None declared
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