Anti-inflammatory and Analgesic Agents from Indian Medicinal Plants

Review
International Journal of Integrative Biology
A journal for biology beyond borders

ISSN 0973-8363

Anti-inflammatory and Analgesic Agents
from Indian Medicinal Plants

Amritpal Singh
1,*
, Samir Malhotra
2
, Ravi Subban
3


1
AyuVeda, Ind-Swift Ltd, Chandigarh, India
2
Dept of Pharmacology, PGIMER, Chandigarh, India
3
Centre for Medicinal plants Research, Arya vaidya sala, kottakkal, Kerala, India

Submitted: 22 May 2008; Accepted: 12 Aug. 2008
Abstract
Inflammatory diseases including arthritis and rheumatism are major group of prevalent diseases. Most of the
available non-steroidal anti-inflammatory drugs are effective in inflammatory conditions of the joints, but are
devoid of gastro protective property. Many substances, interfering with the inflammatory response have been
isolated from Indian medicinal plants (IMP). The review analyses formulations, extracts and phytochemicals
(derived from IMP) evaluated for possible anti-inflammatory activity. Reputed databases and indexed journals
dealing with medicinal plant were consulted for data generation.

Keywords: Alkaloids, anti-inflammatory activity, inflammation, experimental models.


INTRODUCTION INTRODUCTION
Inflammation is the complex biological response
of vascular tissues to harmful stimuli including
pathogens, irritants, or damaged cells. It is a
protective attempt by the organism to remove the
injurious stimuli as well as initiate the healing
process for the tissue (Denko, 1992). The process
of inflammation is necessary in healing of
wounds. Inflammation however, if runs
unchecked, lead to onset of diseases like
vasomotor rhinnorhoea, rheumatoid arthritis and
atherosclerosis (Henson and Murphy, 1989).
Inflammation is the complex biological response
of vascular tissues to harmful stimuli including
pathogens, irritants, or damaged cells. It is a
protective attempt by the organism to remove the
injurious stimuli as well as initiate the healing
process for the tissue (Denko, 1992). The process
of inflammation is necessary in healing of
wounds. Inflammation however, if runs
unchecked, lead to onset of diseases like
vasomotor rhinnorhoea, rheumatoid arthritis and
atherosclerosis (Henson and Murphy, 1989).

Acute inflammation is characterised by classical
signs- edema, erythrema, pain, heat, and above
all, loss of function. The classical signs are
triggered by the infiltration of the tissues by
serum and white blood corpuscles (leucocytes).
Chronic inflammation results in a progressive
shift in type of cells, present at site of
inflammation. It is characterized by simultaneous
destruction and healing of the injured tissue from
incidence of inflammation.
Acute inflammation is characterised by classical
signs- edema, erythrema, pain, heat, and above
all, loss of function. The classical signs are
triggered by the infiltration of the tissues by
serum and white blood corpuscles (leucocytes).
Chronic inflammation results in a progressive
shift in type of cells, present at site of
inflammation. It is characterized by simultaneous
destruction and healing of the injured tissue from
incidence of inflammation.

According to Evans (1992), the cellular
processes of inflammation fall into four distinct
categories: a) Changes in blood flow caused by
changes in smooth muscle cell function causing
vasodilatation. b) Alterations in vascular
permeability engendered by cytoskeletal
contraction in endothelial cells. c) Migration of
phagocytic leukocytes to the site of inflammation.
According to Evans (1992), the cellular
processes of inflammation fall into four distinct
categories: a) Changes in blood flow caused by
changes in smooth muscle cell function causing
vasodilatation. b) Alterations in vascular
permeability engendered by cytoskeletal
contraction in endothelial cells. c) Migration of
phagocytic leukocytes to the site of inflammation.
d) Phagocytosis. d) Phagocytosis.

Early inflammatory changes in damaged tissues
are now known to involve the release of various
biologically active materials from polymorph
nuclear leukocytes, lysosomal enzymes and
others. The vascular effects are primarily
mediated by kinins, prostaglandins and
vasoactive amines (histamine) released by mast
cells. Vasoactive amines cause increased
vascular permeability leading to plasma
exudation. The inflammatory process involves a
complex interplay between cells of the blood, the
blood vessels themselves and the cells of the
involved tissue. The process can be seen as a
coordinated response of a large number of cells
to an initial stimulus (Henson and Murphy,
1989).
Early inflammatory changes in damaged tissues
are now known to involve the release of various
biologically active materials from polymorph
nuclear leukocytes, lysosomal enzymes and
others. The vascular effects are primarily
mediated by kinins, prostaglandins and
vasoactive amines (histamine) released by mast
cells. Vasoactive amines cause increased
vascular permeability leading to plasma
exudation. The inflammatory process involves a
complex interplay between cells of the blood, the
blood vessels themselves and the cells of the
involved tissue. The process can be seen as a
coordinated response of a large number of cells
to an initial stimulus (Henson and Murphy,
1989).

*
Corresponding author:
Amrit Pal Singh, Ph.D.
Ind-Swift Ltd, SCO: 102, Sec 47-C,
Chandigarh-160047,India
Email: amritpal2101@yahoo.com

Inflammation research involves a number of
experimental models to study the anti-
Inflammation research involves a number of
experimental models to study the anti-
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Anti-inflammatory and Analgesic Agents from Indian Medicinal Plants
inflammatory activity. According to Lewis,
(1989), these models are of two types: Acute
inflammatory models and Chronic inflammatory
models.

Acute models are designed to test drugs that
modulate erythema, changes in vascular
permeability, leukocyte migration and
chemotaxis, phagocytosis - polymorphonuclear
leucocytes and other phagocytic cells,
measurement of local pain, antipyretic activity,
local analgesic action and rat paw edema
(Barbosa-Filho et al. 2006).

Chronic models are designed to find drugs that
may modulate the disease process and these
include sponge and pellet implants and
granuloma pouches which deposit granulation
tissue, adjuvant induced arthritis and rabbit
mono-articular arthritis which have an immune
etiology (Lewis, 1989).

It is well known that several physiological
changes play key role in initiating inflammation
in disorders like arthritis and rheumatism. These
responses to inflammation include hyperpyrexia,
increased total leucocyte count (TLC) and
differential leucocyte count (DLC), elevated
erythrocytic sedimentation rate (ESR) and c-
reactive proteins. These are referred to as
markers of acute inflammation (Henson and
Murphy, 1989).

Natural products have long been recognized as
an important source of therapeutically effective
medicines (Cragg et al. 1997). Different
approaches used to analyze the anti-
inflammatory potential of plant and plant-derived
compounds have been developed in the past
years (Handa et al., 1992). Further, traditional
herbal medicines like Commiphora mukul,
Boswellia serrata, Harpagophytum procumbens,
and Pluchea indica have been used for analgesic
effect with success (Vohora and Dandiya, 1992).
Anti-inflammatory and analgesic
phyto-products from Traditional
Medicine
Arthritis and rheumatism are well-defined
diseases of the musculoskeletal system. Before
the availability of synthetic drugs, man was
completely dependent on medicinal plants for
curing diseases. With synthesis of aspirin in 19
th

Century, a new era started in the history of anti-
inflammatory and analgesic drugs (Vane, 1971).
Hippocrates prescribed leaves and bark from
willow tree to relieve fever and pain (Julkunen-
Tuto and Tahvanainen, 1989). In 200 B.C, native
people of North America learn to make salicylate
pain remedies from birch bark (Schmid and
Heide, 1995). Salicin, a glycoside, isolated from
Salix alba L. (Saliaceae) attracted the researchers
and it provided the modern science with acetyl-
salicylic acid. Inside the human system, the
salicin splits up into aglycone and salicylic acid.
Salicin is devoid of inducing gastritis unlike
acetyl salicylic acid (Rainsford and Whitehouse,
1980).
Fig. 1: Structure of Salicin

Practitioners of Traditional Indian Medicine
(TIM), use formulations for anti-inflammatory,
analgesic and anti-rheumatic action with
considerable success (Chatterjee and Pal, 1984).
Dashmoola (combination of roots of ten plants)
is standard Ayurvedic remedy for inflammatory
diseases (Sharma et al., 1973). Scientific studies
on traditional formulations like Rasonadi kvatha
(Kishore and Banerjee, 1973), Maharasnadhi
quath (Thabrew, et al., 2003), Cheriya rasnadi
kashayam (Valarmati et al. 2004) and Triphala
(Rassol and Sabina, 2005) have justified there
role in the treatment of arthritis.

Commiphora mukul (Hook. ex Stocks) Engl.
(Burseaceae), traditionally known as guggul, has
figured high in the treatment of arthritis. Animal
models have demonstrated anti-inflammatory
activity of crude drug and standardized extracts
containing guggulsterones (Arora, 1972; Sharma,
1977). Clinical trials have justified the utilization
of the drug in the treatment of rheumatoid
arthritis (Vyas, 1987) and osteoarthritis (Singh et
al., 2003). Recent works on poyl-herbal
formulations; Triphala Guggul and Yograja
Guggul have reported the immunomodulator
(Shukla et al., 1986) and cartilage-protective
(Sumantran et al., 2007) activities.

The present review is dedicated to polyherbal
formulations (used as anti-inflammatory and
analgesic agents in Ayurveda), extracts and the
bioactive or active constituents isolated and
identified from the Indian medicinal plants,
which have been previously reported to have an
anti-inflammatory activity. Polyherbal
formulations, extracts and the bio-actives have
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Anti-inflammatory and Analgesic Agents from Indian Medicinal Plants
been selected, and the data has been presented on
basis of pharmacological activity in different
experimental models.

Table 1:. Summary on Ayurvedic formulations showing anti-
inflammatory activity
MATERIALS AND METHODS
The key words for the present preview were anti-
inflammatory activity plus formulations and
bioactive (active constituents) of Indian
Medicinal Plants. Chemical Abstracts, Pub-Med,
MAPPA (Medicinal and Aromatic Plants
Program), ABIM (Annotated Bibliography of
Indian Medicine) and data bank on Indian
Medicinal Plants provided by Central Council of
Research in Ayurveda and Siddha (CCRAS),
were used for searching data, updated until May
2008 and updated.
Ayurvedic formulations with anti-
inflammatory and analgesic activity
Summary on Ayurvedic formulations showing
anti-inflammatory activity is shown in Table 1.
Indian medicinal plants with anti-
inflammatory and analgesic activity
Acacia farnesiana (Linn.) Willd. (Fabaceae)
In previous studies, anti-inflammatory effect of
glycosidal fraction of A. farnesiana was reported
(Trivedi et al., 1986). In a study, the ethanolic
extract of leaves of A. faresiana was tested for
the anti-inflammatory activity by carrageenan
induced paw oedema for acute inflammation and
cotton pellet induced granulation for chronic
inflammatory model. The ethanolic extract
showed significant anti-inflammatory activity in
both the models studied (Hukkeri et al., 2002).
Adhatoda vasica Nees (Acanthaceae)
The anti-inflammatory activity of the methanol
extract o the leaves, the non-alkaloid fraction,
the saponins and the alkaloids was evaluated by
the modified hen's egg chorioallantoic
membrane test. The alkaloid fraction showed
potent activity at a dose of 50 microg/pellet
equivalent to that of hydrocortisone while the
MeOH extract and the other fractions showed
less activity (Chakraborty and Brantner, 2001).
Aegle marmelos Corr. (Rutaceae)
Ethyl acetate and methanol extracts of leaves A.
marmelos were screened for in vivo anti-
inflammatory activity in albino rats. Methanol
extract of A. marmelos showed significant anti-
inflammatory activity at a dose of 100 mg/kg
(Gurulingappa et al., 2002).
Alstonia macrophylla Wall. ex A.DC.
(Apocynaceae)
Methanolic extract of dried leaves of A.
macrophylla and its fractions were investigated
for its anti-inflammatory activity. The extract at
a concentration of 200 mg kg
–1
and 400 mg kg
–1
,
p.o. and its fractions at 25 mg kg
–1
and 50 mg
kg
–1
, p.o. showed the significant dose dependent
anti-inflammatory activity in carrageenan and
dextran-induced rats hind paw edema (acute
models) as well as in cotton pellet-induced
granuloma (chronic model) in rats. Anti-
inflammatory activity of the tested extract and its
fractions was comparable with that of the
standard drug Indomethacin at a concentration of
10 mg kg
–1
(Arunachalam et al., 2002).
Ammania baccifera Linn.
The analgesic activity of the ethanol extract of
roots of A. baccifera whole plant was
investigated in chemical models of nociception
in mice. A. baccifera at doses of 200, 400 and
Cheriya rasnadi
kashayam
Anti arthritic
Valarmati et al.,
2004
Maharasnadhi
quath
Anti-inflammatory
& analgesic
Thabrew,
Dharmasiri &
Senaratne, 2003
Narayan taila Anti-inflammatory Patil et al., 2001
Rasnadiguggulu Anti-rheumatic
Shukla et al.,
1985
Rasonadi kvatha Anti-rheumatic
Kishore &
Banerjee,1973
Sinhanad guggul Anti-inflammatory Patil et al., 2001
Sunthi guggulu Anti-rheumatic
Kishore et al.,
1982
Suvarnamakshika
di wati
Analgesic
Joshi & Shrotri,
1995
Triphala Anti-inflammatory
Rassol &,
Sabina, 2005
Triphala guggul Immunomodulator
Shukla et al.,
1986, Sumantran
et al., 2007
Vachadi guggulu Anti-rheumatic
Chandrasekhara,
1966
Vyoshadi guggulu Anti-rheumatic
Chandrasekhara,
1966
Yograja guggul
Cartilage-
protective
Shukla et al.,
1986
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Anti-inflammatory and Analgesic Agents from Indian Medicinal Plants
600mg/kg i.p produced an inhibition of 20.7%,
43.4% and 72.9%, respectively, of the abdominal
writhes induced by acetic acid in mice. In the
formalin test, the administration of 200, 400 and
600mg/kg i.p had no effects in the first phase but
produced a dose-dependent analgesic effect on
the second phase with inhibitions of the licking
time of 27.3%, 47.7% and 57.4%, respectively.
These observations suggest that A. baccifera
possesses some analgesic activity (Dhanapal et
al., 2004).
Anacardium occidentale Linn. (Anacardiaceae)
Hydrolysable and non-hydrolysable tannins
obtained from the bark of A. occidentale on i.p.
injection, demonstrated apparent anti-
inflammatory activity in carrageenan- and
dextran-induced rat paw oedemas, cotton pellet
granuloma test and adjuvant-induced
polyarthritis in rats. At higher doses orally
administered tannins also had activity in
carrageenan paw oedema and adjuvant arthritis
experiments. The tannins i.p. also inhibited
acetic acid-induced "writhing responses" in mice
and were found to antagonise the permeability-
increasing effects in rats of certain mediators of
inflammation and to inhibit the migration of
leucocytes to an inflammatory site (Mota et al.,
1985).
Arnebia euchroma (Royle) Johnston
(Boraginaceae)
The petroleum ether, chloroform, alcoholic and
aqueous extracts of A. euchroma roots (500
mg/kg, orally each) were found to exhibit
maximal edema inhibition: 61.2%, 45%, 27.5%
and 60%, respectively against carrageenin-
induced rat-paw edema at 300 min interval. The
activity shown by different extracts was
comparable to that shown by the reference drug,
ibuprofen: 50 mg/kg, p.o., 61.6% inhibition, 200
min (Kaith et al., 1996).
Atalantia monophylla Corr.(Rutaceae)
Ethyl acetate extract of A. monophylla were
screened for in vivo anti-inflammatory activity in
albino rats. The extract of A. monophylla showed
significant anti-inflammatory activity at a dose
of 100 mg/kg (Gurulingappa et al., 2002).
Azadirachta indica A Juss. (Meliaceae)
The water soluble part of alcoholic extract of A.
indica leaves at a dose of 200 mg/kg, p.o.,
exerted significant anti-inflammatory activity in
cotton pellet granuloma assay in rats. The extract
also inhibited significantly the biochemical
parameters (viz. DNA, RNA, lipid peroxide, acid
phosphatase and alkaline phosphatase) studied in
cotton pellet exudates (Chattaopadhyay, 1998).
Betula alnoides Buch.-Ham. ex D.Don
The extract of B. alnoides was also evaluated for
anti-inflammatory activity in sheep RBC induced
sensitivity and in membrane stabilization models.
Except for the sheep RBC induced sensitivity
model, the extract showed significant anti-
inflammatory activity (Sur et al., 2002).
Bryonia laciniosa Linn. (Cucurbitaceae)
The chloroform extract of roots of B. laciniosa
exhibited significant anti-inflammatory effect at
the dose 50, 100 and 200 mg/kg. Maximum
inhibition (52.4%) was noted at the dose of 200
mg/kg after 3 h of drug treatment in carrageenan
induced paw oedema, whereas the indomethacin
(standard drug) produced 62.1% of inhibition.
The extract exhibited significant anti-
inflammatory activity in dextran induced paw
oedema in a dose dependent manner. The extract
also exhibited significant inhibition on the hind
paw oedema in rats caused by histamine and
serotonin respectively. In cotton pellet induced
granuloma B. laciniosa (200 mg/kg) and
standard drug (phenylbutazone) showed
decreased formation of granuloma tissue by 50.1
and 57.3% (p<0.001) respectively. The extract
also inhibited peritoneal leukocyte migration in
mice (Gupta et al., 2003).
Cassia fistula Linn. (Fabaceae)
C. fistula leaves were tested for anti-
inflammatory effects, as compared with
phenylbutazone, using carrageenin, histamine,
and dextran induced paw edema in rats. Potent
anti-inflammatory activity against all phlogistic
agents was noted (Bhakta et al., 2000).
Cedrus deodara (Roxb.) Loud. (Pinaceae)
The volatile oil extracted by steam distillation of
the wood of C. deodara was examined for its
oral anti-inflammatory and analgesic activity at
the doses of 50 and 100 mg/kg body weight. It
produced significant inhibition of carrageenan-
induced rat paw edema and of both exudative-
proliferative and chronic phases of inflammation
in adjuvant arthritic rats at doses of 50 and 100
mg/kg body weight. The oil at both tested doses
was found to possess analgesic activity against
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Anti-inflammatory and Analgesic Agents from Indian Medicinal Plants
acetic acid-induced writhing and hot plate
reaction in mice (Shinde et al., 1999).
Cissampelos pareira
In the present study, 50% ethanolic extract of C.
pareira roots (CPE) in acute, subacute and
chronic models of inflammation was assessed in
rats. Per os (p.o.) administration of C. pareira at
200, 400 mg/kg exhibited significant anti-
inflammatory activity. In acute inflammation as
produced by carrageenin 59.55% and 64.04%, by
histamine 15.38% and 30.77%, by 5-
hydroxytryptamine 17.78% and 31.11% and by
prostaglandin E-induced hind paw edema
19.23% and 30.77% protection was observed.
While in subacute anti-inflammatory models
using formaldehyde-induced hind paw edema
(after 1.5 h) 38.36% and 47.95% and in chronic
anti-inflammatory model using cotton pellet
granuloma 15.02% and 19.19% protection from
inflammation was observed. C. pareira did not
show any sign of toxicity and mortality up to a
dose level of 1000 mg/kg, p.o. in rats. Both acute
as well as chronic administration of C. pareira
(100, 200 and 400 mg/kg, p.o.) did not produce
any gastric lesion in rats (Amresh et al., 2007).

In yet another study, 50% aqueous ethanolic
extract of C. pareira at the dose levels of 100–
400 mg/kg, once daily for 3 days exhibited
significant (P < 0.001) resistance against
mechanical pain after 30 min in analgesymeter
induced pain in mice. In acetic acid (0.6%; i.p.)
inducing writhing, C. pareira significantly
(P < 0.05) decreased the writhing episodes; the
degree of percent protection at 200 and
400 mg/kg was 22.73 and 51.63. The hot plate
reaction time was increased by 2.07 (P < 0.05)
and 2.70 (P < 0.001) folds respectively. Further
C. pareira showed the dose dependent
significant protective effect against complete
Freund's adjuvant induced arthritis. The
percentage protection on the 18th day was 40.54
(P < 0.01) and 71.52 (P < 0.001) at 200 and
400 mg/kg respectively. Lysosomal enzymes
(acid phosphatase and N-acetyl glucosaminidase)
were decreased by 50% (P < 0.01) and 26.26%
(P < 0.05) by using C. pareira, dextramethasone
decreased them 56.56% (P < 0.01) and 31.82%
(P < 0.01) and the glycoprotein contents (total
hexose and sialic acid) were increased by 1.55-
folds (P < 0.01) and 1.51-folds (P < 0.05) by
using C. pareira while dextramethasone
increases them by 1.51-folds (P < 0.001) and
1.60-folds (P < 0.01) respectively in stomach
homogenate with respect to arthritic group. The
increased pain threshold and protective effect
against carrageenan induced footpad edema by C.
pareira vindicated its medicinal value in
treatment of pain and arthritis (Amresh et al.,
2007).
Cissus quadrangularis Linn. (Vitaceae)
The analgesic activity of alcoholic extract of
whole plant of C. quadrangularis family
vitaceae), was studied in mice by Haffner's Clip
and Eddy's hot plate methods. The extract
effective by both oral and i.p. routes significantly
(P < 0.001) increased the reaction time by both
methods. The duration of analgesic activity was
from 2 to 4 h and optimum effect was observed
at l/20th -1/10th of LD50 dose. The extract
compared well with acetylsalicylic acid (Singh et
al., 1984).
Clemone gynandra Linn. (Capparidaceae)
The ethanolic extract of C. gynandra was
administered orally at a dose of 150 mg/kg body
weight for 30 days to the experimental rats after
the induction of adjuvant arthritis. The anti-
inflammatory activity of C. gynandra leaves was
assessed by paw volume measurement, and its
capacity to stabilize lysosomal enzyme activities
in the plasma and liver of control and
experimental rats. The activity of
pathophysiological enzymes such as AST, ALT,
ALP, cathepsin-D, β-glucuronidase, N-acetyl-β-
glucosaminidase LDH and the levels of
glycoproteins were also estimated in plasma and
liver. The increased levels of both lysosomal
enzymes and protein-bound carbohydrates in
arthritic rats were significantly suppressed to
near normal level by the administration of C.
gynandra extract. Further, the significantly
elevated plasma levels of TNF-α found in
arthritic rats were found to be significantly
restored back to near normal levels by the extract
in experimental animals. The membrane
stabilizing activity of the extract was further
evidenced by histological observations made on
the limb tissue (Narendhirakannan, et al., 2005).
Clemone rutidosperma Linn. (Capparidaceae)
Oral administration of the ethanolic extract (200
and 400 mg/kg, p.o) and its fractions (200 mg/kg
each) of the aerial parts of C. rutidosperma
produced significant analgesic activity in acetic
acid-induced writhing and tail immersion tests,
anti-inflammatory effect against carrageenin
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Anti-inflammatory and Analgesic Agents from Indian Medicinal Plants
induced inflammation and adjuvant induced
polyarthritis and antipyretic activity against
yeast-induced pyrexia. Fractionation of the
ethanolic extract potentiated the activities (Bose
et al., 2007).
Curcuma amada Roxb. (Zingiberaceae)
The extract of C. amada was screened for anti-
inflammatory activity in albino rats using acute
carrageenan paw oedema and chronic granuloma
pouch model. The extract exhibited dose
dependant anti-inflammatory activity in acute
and chronic models (Mujumdar et al., 2000).
Dalbergia lanceolaria L.f. (Dalbergieae)
Topical anti-inflammatory activity of D.
lanceolaria bark ethanol extract was
demonstrated in albino mice using TPA-, EPP-
and AA-induced ear edema models. The
systemic activity of extract was confirmed using
acute and sub-acute anti-inflammatory models in
albino rats. The ethanol extract exhibited
significant systemic anti-inflammatory activity in
Carrageenan-induced rat paw edema, by
inhibition of histamine and prostaglandin phases
of acute inflammation. The extract also showed
significant activity against turpentine-induced
exudative changes and no activity against
granular tissue formation in cotton pellet-induced
granuloma in albino rats (Kale et al., 2007).
Drymaria cordata (Linn.) Willd.
(Caryophyllaceae)
The anti-inflammatory effect of the methanol
extract of D. cordata was investigated against
carrageenin, histamine, serotonin, dextran and
PGE₁ induced rat hind paw oedema. It exhibited
significant anti-inflammatory activity against all
these phlogestic agents except PGE₁ It exhibited
significant anti-inflammatory activity against all
these phlogestic agents except PGE 1. All these
effects were compared with standard drug
phenylbutazone in both the acute and chronic
experimental models in albino rats. All these
effects were compared with standard drug
phenylbutazone in both the acute and chronic
experimental models in albino rats (Mukerjee et
al., 1998).
Echinops echinatus Roxb. (Asteraceae)
Anti-inflammatory studies were conducted on an
ethanol extract of E. echinatus whole plant.
Ethanol extract of E. echinatus inhibited the
acute inflammation induced in rats by
carrageenan, formaldehyde and adjuvant and the
chronic arthritis induced by formaldehyde and
adjuvant. The extract was more effective
parenterally than orally (Singh et al., 1989).
Eclipta alba (Linn.) Hassk. (Asteraceae)
The present experimental research work was
undertaken to determine the analgesic activity of
the total ethanol extract of E. alba, and also the
isolated alkaloids of E.alba in albino mice by
using standard experimental models such as the
tail clip method, the tail flick method and the
acetic acid induced writhing response. The
results from this study show that both the ethanol
extract as well as the total alkaloids produce
good analgesic activity in all the different models
of analgesia used. The total alkaloidal fraction
was the most efficacious in all models tested
(Swant, et al., 2004).
Emblica officinalis Linn. (Euphorbiaceae)
A single oral dose of ethanol and aqueous (500
mg/kg, i.p.) of E. officinalis showed significant
reduction in brewer's yeast induced hyperthermia
in rats. Ethanol and aqueous also elicited
pronounced inhibitory effect on acetic acid-
induced writhing response in mice in the
analgesic test. Both, ethanol and aqueous did not
show any significant analgesic activity in the
tail-immersion test. These findings suggest that
extracts of E. officinalis fruits possessed potent
anti-pyretic and analgesic activity (Perianayagam
et al., 2004).
Emilia sonchifolia Linn. (Asteraceae)
Fresh juice and methanolic extract of Emilia
sonchifolia leaves were found to be potent
inhibitors of hydroxyl radical formation and
superoxide radical generation in vitro. The
methanolic extract inhibited the carrageenan-
induced oedema (Shylesh and Padikkala, 1999).
Enicostemma littorale Bl. (Gentianaceae)
The anti-inflammatory activity of whole plant
extract of E. littorale was assessed by
carrageenan-induced inflammation and cotton
pellet granuloma method in rats. E. littorale
exerted 54 % anti-inflammatory activity for a
dose of 100 mg/100 g body wt, in carrageenan-
induced acute inflammation. In chronic
inflammation of cotton pellet granuloma, E.
littorale exerted 30 % anti-inflammatory activity
at the above dosage (Sadique et al., 2000).
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Anti-inflammatory and Analgesic Agents from Indian Medicinal Plants
Ficus racemosa Linn. (Moraceae)
The extract of bark of F. racemosa at doses of
200 and 400 mg/kg has been found to possess
significant anti-inflammatory activity on the
tested experimental models. The extract (400
mg/kg) exhibited maximum anti-inflammatory
effect (30.4, 32.2, 33.9 and 32.0%) at the end of
3 h with carrageenin, serotonin, histamine,
dextran-induced rat paw oedema, respectively. In
a chronic test, the extract (400 mg/kg) showed
41.5% reduction in granuloma weight. The effect
produced by the extract was comparable to that
of phenylbutazone (Mandal et al., 2000).
Hypericum perforatum Linn. (Guttiferae)
A standardized 50% aqueous ethanolic extract of
the Indian variety of H. perforatum was
examined for its putative anti-inflammatory and
analgesic activity at the doses of 100 and 200
mg/kg, po. The experimental paradigms used
were carrageenan induced pedal edema and
cotton pellet induced granuloma for anti-
inflammatory activity, whereas the tail flick, hot
plate and acetic acid induced writhing methods
were used to asses analgesic activity.
Indomethacin (20 mg/kg, ip) was used as the
standard anti-inflammatory drug. Pentazocine
(10 mg/kg, ip) and aspirin (25 mg/kg, ip), both
clinically used analgesics, were used as standard
analgesics for comparison. H. perforatum extract
showed significant anti-inflammatory and
analgesic activity at both dose levels, in all the
paradigms used. Additionally, H. perforatum
potentiated the anti-inflammatory activity of
indomethacin and analgesic activities of
pentazocine and aspirin (Kumar et al., 2001).
Ixora brachiata Roxb (Rubiaceae)
Methanolic extract of the flowers of I. brachiata
was found to possess anti-inflammatory activity
against cotton pellet granuloma in rats at a dose
level of 100 mg/kg body weight, sc. I. brachiata
reduced the protein content, acid phosphatase,
glutamate pyruvate transaminase and glutamate
oxalo-acetate transaminase activities in liver and
serum. A significant reduction in the ascorbic
acid content in adrenals was also observed in
drug-treated animals (Vimala et al., 1997).
Jatropha curcas Linn. (Euphorbiaceae)
Anti-inflammatory activity of topical application
of J curcas root powder in paste form in TPA-
induced ear inflammation was confirmed in
albino mice and the successive solvent extraction
of these roots was carried out by ether and
methanol. The methanol extract exhibited
systemic and significant anti-inflammatory
activity in acute carrageenan-induced rat paw
edema. It also showed activity against formalin-
induced rat paw edema, as well as, turpentine-
induced exudative changes and cotton pellet-
induced granular tissue formation after oral
treatment for 7 days in albino rats. The ether
extract failed to elicit anti-inflammatory actyivity
(Mujumdar and Misar, 2004).
Michelia champaca Linn. (Magnoliaceae)
Methanolic extract of the flowers of M.
champaca was found to possess anti-
inflammatory activity against cotton pellet
granuloma in rats at a dose level of 100 mg/kg
body weight, sc. M. champaca reduced the
protein content, acid phosphatase, glutamate
pyruvate transaminase and glutamate oxalo-
acetate transaminase activities in liver and serum.
A significant reduction in the ascorbic acid
content in adrenals was also observed in drug-
treated animals (Vimala et al.1997).
Mollugo cerviana (L.) Ser. Ex DC.
(Molluginaceae)
The anti-inflammatory activity of M. cerviana
was assessed by carrageenan-induced
inflammation and cotton pellet granuloma
method in rats. M. cerviana exerted 26% anti-
inflammatory activity for a dose of 100 mg/100 g
body wt, in carrageenan-induced acute
inflammation. In chronic inflammation of cotton
pellet granuloma, M. cerviana exerted 46% anti-
inflammatory activity at the above dosage
(Sadique et al., 2000).
Morus indica Linn. (Moraceae)
Anti-inflammatory activity of the ethanolic
extract of the leaves of M. indica was studied in
wistar rats using the carrageenan induced left
hind paw edema, carrageenan induced pleurisy
and cotton pellet induced granuloma model. The
ethanolic extract (100 mg/kg, p.o.) inhibited
carrageenan induced rat paw edema. It also
showed an inhibitory effect on leukocyte
migration and a reduction on the pleural exudates
as well as reduction on the granuloma weight in
the cotton pellet granuloma method
(Balasubramanian et al., 2005).
Nyctanthes arbor-tristis Linn. (Verbenaceae)
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Anti-inflammatory and Analgesic Agents from Indian Medicinal Plants
The water soluble portion of the alcoholic extract
of the leaves of N. arbor tristis was screened for
the presence of anti-inflammatory activity. N.
arbor tristis inhibited the acute inflammatory
oedema produced by different phlogistic agents,
viz. carrageenin, formalin, histamine, 5-
hydroxytryptamine and hyaluronidase in the
hindpaw of rats. The acute inflammatory
swelling in the knee joint of rats induced by
turpentine oil was also significantly reduced. In
subacute models, N. arbor tristis was found to
check granulation tissue formation significantly
in the granuloma pouch and cotton pellet test.
Acute and chronic phases of formaldehyde
induced arthritis were significantly inhibited. N.
arbor tristis was also found to inhibit the
inflammation produced by Freund's adjuvant
arthritis and PPD induced tuberculin reaction
(Saxena et al., 1984).
Ocimum basilicum Linn. (Lamiaceae)
A methanol extract and an aqueous suspension of
O. sanctum inhibited acute as well as chronic
inflammation in rats as tested by carrageenan-
induced pedal edema and croton oil-induced
granuloma and exudate, respectively. In both test
procedures, the anti-inflammatory response of
500 mg/kg of methanol extract and aqueous
suspension was comparable to the response
observed with 300 mg/kg of sodium salicylate.
Both the extract and suspension showed
analgesic activity in the mouse hotplate
procedure and the methanol extract caused an
increase in the tail-withdrawal reaction time of a
subanalgesic dose of morphine. Both
preparations reduced typhoid-paratyphoid A/B
vaccine-induced pyrexia. The antipyretic action
of the methanol extract and aqueous suspension
was weaker and of shorter duration than that of
300 mg/kg sodium salicylate (Godhwani,
Godhwani and Vyas, 1987).
Piper longum Linn. (Piperaceae)
An aqueous suspension of P. longum root
powder is given orally to mice and rat in doses of
200, 400 and 800 mg/kg. The delay in reaction
time for thermal stimulus in rats and the number
of writhings to chemical stimulus in mice are
determined in each group. The results are
analysed statistically. The 400 and 800 mg/kg
doses of P. longum show significant NSAID type
of analgesia (P < 0.001). Both Ibuprofen (40
mg/kg) and P. longum (800 mg/kg) show 50%
protection against writhing. The delay in reaction
time to thermal stimulus was less than 6% for
different doses of P. longum as against 100% for
pentazocine (Vedhanayaki, et al., 2003).
Pluchea indica Less. (Asteraceae)
A methanolic fraction of a chloroform extract of
defatted P. indica roots was investigated for its
anti-inflammatory potential against several
models of inflammation. The extract showed
significant inhibitory activity against
carrageenin-, histamine-, serotonin-,
hyaluronidase- and sodium urate-induced pedal
inflammation. The extract inhibited protein
exudation and leucocyte migration. The extract
also inhibited carrageenin- and cotton pellet-
induced granuloma formation as well as
turpentine-induced joint oedema and adjuvant-
induced polyarthritis (Sen, et al., 1991).
Pongamia pinnata Linn. (Fabaceae)
In a study, the anti-inflammatory activity of 70%
ethanolic extract of P. pinnata leaves in acute,
subacute and chronic models of inflammation
was assessed in rats. Per os (p.o.) administration
of PLE (300, 1000 mg/kg) exhibited significant
anti-inflammatory activity in acute (carrageenin,
histamine, 5-hydroxytryptamine and
prostaglandin E2-induced hind paw edema),
subacute (kaolin-carrageenin and formaldehyde-
induced hind paw edema) and chronic (cotton
pellet granuloma) models of inflammation. P.
pinnata did not show any sign of toxicity and
mortality up to a dose level of 10.125 g/kg, p.o.
in mice. Both acute as well as chronic
administration of P. pinnata (100, 300 and 1000
mg/kg, p.o.) did not produce any gastric lesion in
rats (Srinivasan et al., 2001).
Rhododendron arboreum Smith (Ericaceae)
50% ethanolic and methanolic extracts of
flowers of R. arboreum were investigated against
carrageenan. PG (E2), histamine and 5-HT
induced rat's hind paw oedema. The extracts
exhibited significant anti-inflammatory activity
against all the four phlogistic agents. The
aqueous extracts showed maximum anti-
inflammatory activity followed by 50% ethanolic
and methanolic extracts (Agarwal and Sharma,
1986).
Rhynchosia cana (Willd.) DC.
Methanolic extract of the flowers of R. cana was
found to possess anti-inflammatory activity
against cotton pellet granuloma in rats at a dose
level of 100 mg/kg body weight, sc. R. cana
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Anti-inflammatory and Analgesic Agents from Indian Medicinal Plants
reduced the protein content, acid phosphatase,
glutamate pyruvate transaminase and glutamate
oxalo-acetate transaminase activities in liver and
serum. A significant reduction in the ascorbic
acid content in adrenals was also observed in
drug-treated animals. R. cana was recorded to
possess significant antipyretic activity from the
first hour of administration (Vimala et al., 1997).
Ricinus communis Linn. (Euphorbiaceae)
Petroleum ether extract of R. communis exhibited
significant anti-inflammatory activity against
(Formaldehyde and adjuvant induced rat's paw
arthritis). R. communis (150 mg/kg po) exhibited
no significant analgesic activity. R. communis
was safe upto a dose of 1 g/kg p.o. in rats
(Banerjee et al., 1991).
Sida cordifolia Linn. (Malvaceae)
The ethyl acetate extract of root of S. cordifolia
showed comparable anti-inflammatory activity
with indomethacin and possessed significantly
higher activity when compared with that of the
methanol extract of the root part. The ethyl
acetate extract of both root and aerial parts of S.
cordifolia showed very good central and
peripheral analgesic activities at a dose of 600
mg/kg. The methanol extract of root (SCR-M)
was found to possess significant hypoglycaemic
activity (Kanth and Diwan, 1999).
Sida rhombifolia Linn. (Malvaceae)
In an animal study, anti-inflammatory of the
methanolic extract of the aerial parts of S.
rhombifolia was studied. Oedema was induced
by carrageenan and the oedema suppressant
activity was measured using a plethysmometer.
The methanolic extract of the aerial parts showed
significant anti-inflammatory activity in rats. The
researchers concluded that the anti-inflammatory
activity of S. rhombifolia was due to the
inhibitory effects on the release of histamine like
substances (Rao and Mishra, 1997).
Spilanthes acemella (Asteraceae)
S. acemella was evaluated for anti-inflammatory
action by carrageenan-induced rat paw edema.
The analgesic activity was tested by acetic acid-
induced writhing response in albino mice and tail
flick method in albino rats. The aqueous extract
of S. acemella in doses of 100, 200 and 400
mg/kg showed 52.6, 54.4 and 56.1% inhibition
of paw edema respectively at the end of three
hours and the percentage of protection from
writhing was 46.9, 51.0 and 65.6 respectively. In
the tail flick model, the aqueous extract of S.
acemella in the above doses increased the pain
threshold significantly after 30 min, 1, 2 and 4 h
of administration. S. acemella showed dose-
dependent action in all the experimental models
(Chakraborty et al., 2004).
Teramnus labialis (L.) Spreng. (Fabaceae)
Bioassay-guided fractionation, based on anti-
inflammatory activity of the methanolic
extractives of T. labialis led to the isolation and
characterization of vitexin, bergenin, daidzin and
3-O-methyl-D- chiro -inositol as active
constituents. Vitexin exhibited a dose-dependent
inhibitory activity on 5-lipoxygenase enzyme
(Sridhar, et al., 2006).
Vernonia cinerea Ness. (Asteraceae)
An alcoholic extract from the flower of V.
cinerea change was investigated for anti-
inflammatory activity. Changes in paw volume,
body and tissue weights and serum and tissue
enzyme activities of ALT, AST, ACP and
cathepsin-D in adjuvant rats were reversed by
oral administration of 100 mg/kg body weight
(BW) of the flower extract. 3. The extract also
reversed the major histopathological changes in
the hind paws of the arthritic rats (Latha, et al.,
1998).
Vitex negundo Linn. (Verbenaceae)
Analgesic activity of V. negundo leaf extract
(500 and 1000 mg/kg) was studied using acetic
acid induced writhing test in mice for assessing
peripheral analgesic effect and tail immersion
test in mice for assessing central analgesic effect.
The anti-inflammatory activity of VLE (500 and
1000 mg/kg) was studied by using the models of
carrageenin-induced rat paw oedema and
carrageenin-induced granuloma pouch in rats for
assessing the effect on acute and sub acute
inflammations, respectively. V. negundo
significantly increased the reaction time and
decreased the writhing movements in mice in
acetic acid-induced writhing test. There was a
significant increase in the reaction time in tail
immersion test. V. negundo significantly
decreased the rat paw oedema volume at higher
dose. It also significantly decreased the
formation of granuloma pouch in rats (Telang, et
al., 1999).

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Anti-inflammatory and Analgesic Agents from Indian Medicinal Plants
Database search provided brief information on
several medicinal plants which have been
evaluated for anti-inflammatory and analgesic
activities in animal models. These have been
tabulated in Table 3 [Supplementary data].
Active constituents reported from
Indian medicinal plants with anti-
inflammatory and analgesic activity
(+)-pinitol
In the carrageenin-induced paw oedema in rats,
(+)-pinitol at a dose of 2.5-10 mg/kg, i.p.),
isolated from Abies pindrow Royle. (Pinaceae)
leaves, showed a significant anti-inflammatory
effect, the highest dose being comparable to
phenylbutazone at a dose of 100 mg/kg, i.p.
(Singh et al., 2001).
Achyranthine
The water-soluble alkaloid, achyranthine isolated
from Achyranthes aspera L. (Amaranthaceae)
was screened for its anti-inflammatory and anti-
arthritic activity against carrageenin-induced foot
oedema, granuloma pouch, formalin induced
arthritis and adjuvant arthritis in rats. It showed
significant anti-inflammatory activity in all the
four models employed but was less active than
phenylbutazone and betamethasone. Incidence of
gastric ulcers was maximum with betamethasone
and minimum with achyranthine (Neogi et al.,
1969).
Agnuside and pedunculariside
A new iridoid, pedunculariside, together with the
known iridoid agnuside were isolated from the
butanol extract of Vitex peduncularis Wall. ex
Schauer (Verbenaceae) stem bark. Both
pedunculariside and agnuside showed
preferential inhibition of COX-2, with IC50
values of 0.15 +/- 0.21 mg/ml and 0.026 +/-
0.015 mg/ml respectively, while having only
small inhibitory effects on COX-1 (Suksamrarn
et al., 2002).
Androgrpaholide
Andrographolide, diterpene lactone from
Andrographis paniculata (Burm.f.) Wall. ex
Nees (Acanthaceae) exerts its anti-inflammatory
effects by inhibiting NF-KB binding to DNA,
and thus reducing the expression of COX-2
(Madhav et al., 1996).
Betulinic acid
Betulinic acid, a triterpene isolated from
Nelumbo nucifera Linn. (Nymphaceae)
demonstrated significant anti-inflammatory
activity when tested in carrageenin and 5-
hydroxytryptamine induced paw edema. The
activity was comparable to betamethasone and
phenylbutazone (Mukherjee et al.1997).
Cerpegin
Cerpegin, a novel furopyridine alkaloid isolated
from the plant Cerpegia juncea Roxb.
(Asclepiadaceae) was subjected to various
pharmacological investigations. A dose-related
analgesic effect was observed in mice. Cerpegin
did not produce any autonomic or behavioral
changes up to a dose of 200 mg/kg but doses of
more than 400 mg/kg produced excitation and
later convulsions in mice (Sukumar, et al., 1966).
Crotalaburnine or anacrotine
Anti-inflammatory activity of crotalaburnine or
anacrotine isolated from Crotalbria laburnifolia
Linn. (Fabaceae) was investigated against
several models of inflammation. The effect was
compared with the activity of hydrocortisone,
phenylbutazone, sodium salicylate and
cyproheptadine against different types of
inflammation. Crotalaburnine (40 mg/kg s.c. × 5
alternate days) had no significant inhibitory
effect against formalin-induced arthritis, while
hydrocortisone (40 mg/kg s.c. × 10 days) was
effective from the fifth day onwards. Against
carrageenin-induced oedema both crotalaburnine
(10 mg/kg s.c.) and phenylbutazone (100 mg/kg
oral) produced a similar degree of inhibition.
Hydrocortisone (10 mg/kg s.c.) produced slightly
greater inhibition (Ghosh and Singh, 1974).
Curcumin
Curcumin was found to inhibit arachidonic acid
metabolism, cyclooxygenase, lipoxygenase,
cytokines (Interleukins and tumour necrosis
factor) Nuclear factor-kB and release of steroidal
hormones. Curcumin was reported to stabilize
lysosomal membrane and cause uncoupling of
oxidative phosphorylation besides having strong
oxygen radical scavenging activity, which was
responsible for its antiinflammatory property. In
various animal studies, a dose range of 100-200
mg/kg body weight exhibited good
antiinflammatory activity and seemed to have
negligible adverse effect on human systems
(Kohli et al., 2005).
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Anti-inflammatory and Analgesic Agents from Indian Medicinal Plants
Gangetin
Gangetin, pterocarpene flavonoid, isolated from
the hexane extract of the root of the Desmodium
gangeticum (L.)DC. Var maculatum (L.) Baker
(Fabaceae) showed significant anti-inflammatory
activity in the exudative and the proliferative
phases of inflammation in the doses of 50 and
100 mg/kg orally. The compound showed
significant analgesic activity (Ghosh and
Anadakumar, 1981).
Gossypin
Gossypin, found in Hibiscus vitifolius Linn.
(Malvaceae) was found to significantly reduce
the rat paw, edema and the increased vascular
permeability induced by various phlogistic
agents. It produced significant inhibition of the
accumulation of pouch fluid and granulation
tissue formation in the carrageenin induced
granuloma pouch in rats. Gossypin was also
found effective against the adjuvant and formalin
induced chronic arthritis in rats (Parmer and
Ghosh, 1978).
Hedychenone
Pharmacological investigations on rhizomes of
Hedychium spicatum Buch.-Ham. (Zingiberaceae)
indicated anti-inflammatory and analgesic
activites. The anti-inflammatory activity was
localised mainly in the hexane fraction from
which one of the pure active constituents,
hedychenone, a terpene has been isolated. The
analgesic activity was more prominent in the
benzene fraction (Srimal et al., 1984).
Premnazole
Premnazole, an isoxazole alkaloid isolated from
Premna integrifolia L. and Gmelina arborea L.
(Verbenaceae) demonstrated significant anti-
inflammatory activity in reducing cotton pellet-
induced granuloma formation in rats. The anti-
inflammatory activity was comparable to that of
phenylbutazone (Barik et al., 1979).
Tylpohorine
Experiments conducted with tylpohorine, a
phenanthroindalizidine alkaloid, present in
Tylophora asthmatica (L. f.) Wight and Arn.
(Asclepiadaceae) in various animal models have
shown significant anti-inflammatory, anti-
anaphylactic and anti-spasmodic activities
(Gopalakrishnan, et al., 1979).
Withaferin A
Withaferin-A, steroidal lactone from Withania
somnifera Dunal. (Solanaceae) exhibited fairly
potent anti-arthritic and anti-inflammatory
activities. It was found to suppress arthritic
syndrome without any toxic effect. Unlike
hydrocortisone-treated animals which lost weight,
the animals treated with withaferin A showed
gain in weight in arthritic syndrome. It is
interesting that withaferin A seems to be more
potent than hydrocortisone in adjuvant-induced
arthritis in rats, a close experimental
approximation to human rheumatoid arthritis. In
its oedema-inhibiting activity, the compound
gave a good dose-response in the dose-range of
12-25 mg/kg. body-wt. of albino rats
intraperitoneally and a single dose had a good
duration of action, as it could effectively
suppress the inflammation after four hours of its
administration (Sethi et al., 1970). Database
search provided brief information on several
medicinal plants which have been evaluated for
anti-inflammatory and analgesic activities in
animal models (Table 3 [Supplementary data]).
DISCUSSION
Literature research afforded several plants
(single or poly-herbal), extracts and active
constituents with significant anti-inflammatory
activity. Limited data accumulated for analgesic
and anti-rheumatic activity. Among polyherbal
formulations, guggul was the ‘principal
medicinal drug’. They are active against several
model of inflammation but carragenin induced
pedal edema seems to be commonly employed
method (Biren et al. 2006). In one study, the
mild laxative formulation, Triphala was reported
to have significant anti-inflammatory (Rassol
and Sabina, 2005).

Majority of the active constituents, were
identified as alkaloids, flavonoids and rarely
xanthones and sterols. Guggulsteones, boswellic
acid, curcumin, withaferin–A, and
andrographolide have been reported to be
promising anti-inflammatory agents in animal
models. Experts are of the view that there is not
acute shortage of leads for developing anti-
inflammatory drugs. We need to initiate pending
work on these phyto- constituents with emphasis
on side-effect profile (Biren et al., 2006).

The studies are valuable for identifying lead
compounds for anti-inflammatory drugs, keeping
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Anti-inflammatory and Analgesic Agents from Indian Medicinal Plants
in mind the side effects of non-steroidal anti-
inflammatory drugs and corticosteroid
(Majumdar1971; Singh, 1993). Animal data is
valuable for developing cost effective and
efficacious anti-inflammatory agents. This
further supports the correlation of reverse
pharmacology with Ayurvedic drug actions
(Vaidya, 2006). The studies provide little data
pertaining to side effect profile of phyto-drugs,
keeping in mind the unpleasant effects of non-
steroidal anti-inflammatory drugs (Biren et al.,
2006). To add, clinical trials are warranted to
justify the ancient and pre-clinical findings about
anti-inflammatory agents.
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