WORetLal.

D JOURNAL OF
PHAJournal
RMAC
AND PH
ARPharmaceutical
MACEUTICSciences
AL SCIENCES
Ghulam
World
ofYPharmacy
and
SJIF Impact Factor 2.786

Volume 3, Issue 11, 272-310.

Review Article

ISSN 2278 4357

PRESENT STATUS OF ANTIINFLAMMATORY AND ANTI

RHEUMATIC PHYTOCONSTITUENTS: A REVIEW
Bader G.N*, Mir P.A., & Bhat Z.A.
Department of Pharmaceutical Sciences, University of Kashmir, Hazratbal Srinagar, India.

Article Received on
05 September 2014,
Revised on 26 September
2014,
Accepted on 16 October
2014

ABSTRACT
Herbs and herbal medicine have not been studied in the same way that
prescription medicine for rheumatoid arthritis (RA) have. There is a
tremendous disconnect between their widespread usage and peoples
belief in their efficacy compared to what has been proven

*Correspondence for
Author
Dr. Ghulam Nabi Bader

scientifically. Many herbs/their extracts have been used as antirheumatic agents by practitioners of alternate system of medicine

Department of

(mainly Unani and Ayurvedha). Use of these herbal medicines is

Pharmaceutical Sciences,

based on the anti-rheumatic phytoconstituents present in them. This

University of Kashmir,

article is a compilation of different phytoconstituents used as anti-

Srinagar-190006

rheumatic drugs or are drugs under investigation for the same

purpose.
Key words: Rheumatoid arthritis, Unani and Ayurvedha.
ALKALOIDS
1. Tetrandrine: It is chemically a bis-benzylisoquinoline alkaloid which is a natural
analogue of berbamine and is extracted from the tuberous roots of creeper Stephania
tetrandra & S. moore (Menispermaceae). It is used for the treatment of rheumatic diseases
and is also efficacious in silicosis associated with inhibition of collagen synthesis. It inhibits
neutrophil and monocyte locomotion and lymphocyte transformation. Tetrandrine suppresses
the release and activity of inflammatory cytokines, lipid mediators, histamine and has an
inhibitory capacity on monocytes to produce tumor necrosis factor (TNF)-. Tetrandrine is
considered as a prototypic tool compound for the development of new class of anti-rheumatic
agents [1, 2].

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Tetrandrine
2. Berbamine: It is an isoquinoline alkaloid obtained from Berberis vulgaris. It is also found
to have significant inhibitory activity on prostaglandin E2 (PGE2) generation, with stronger
inhibitory effects on natural-killer cell population.[3]

Berbamine
3. Sinomenine (SIN): This bioactive alkaloid derived from the Chinese medicinal plant,
Sinomenium acutum (Menispermaceae) was Investigated on collagen-induced arthritis (CIA)
in mice at varying doses (s.c) for 55 days. The severity of arthritis was evaluated according to
clinical score. The results showed that treatment with SIN was followed by decreases in the
incidence and severity of CIA, anti-CII IgG and the antigen-specific splenocyte proliferation.
Production of all isotypes of antibodies including anti-CII IgG2a, IgG1 and IgE as well as
secretion of cytokines such as IFN- (interferon gamma) and IL-5 were suppressed by SIN.
In addition, SIN enhanced the secretion of TGF- (transforming growth factor beta) while it
had no obvious effect on production of IL-10. These results suggest that the anti-arthritic
effect of SIN may be related to the suppression of both Th1 and Th2 (T helper lymphocyte 1
& 2) immune responses. TGF- may at least in part contribute to the suppression of Th1 as
well as Th2 immune responses.[4]

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Sinomenine
4.Stachydrine: It is a crystalline alkaloid from Capparis spinosa L. (Capparidaceae) fruits.
It has been used as anti-arthritic. The adjuvant arthritic rat model was developed to evaluate
the anti-arthritic effects of different fractions of ethanol extract from C. spinosa L. The
fraction eluted by ethanol-water (50:50, v/v) had the most significant anti-arthritic activity
which contained stachydrine.[5]

Stachydrine
5.Colchicine: This alkaloid is present in corns and seeds of crocus like plants and is an
established clinical agent for arthritic disease and leukocytoclastic vasculitis[6]. Best known
for its preventive action against gout, it also reduces pain and swelling in degenerative and
immunological inflammatory disease[7].

Colchicine
6.Aconitine: This alkaloid from the main root of Aconitum carmichaeli has marked
suppressive effect on the swelling of rat's hind paw induced by injections of fresh egg protein,
carrageenin, histamine and 5-HT, on the mouse's ear oedema induced by bimethylphenyl, on
the exudate and proliferation of granulation tissue of granuloma pouch induced by croton oil,
on the leukocyte migration and on the contents of PGE in the exudate of the swelling hind
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paw induced by injecting carrageenan. Aconitine has been found useful in inhibiting
significantly such immune inflammations as reversible passive arthus reaction, rat's delayed
skin hypersensitivity and adjuvant arthritis.[8]

Aconitine
7.Bukittinggine: This major alkaloid of Sapium baccatum Roxb. (Euphorbiaceae) exhibited
a significant inhibitory effect in carrageenan-induced hind paw oedema and adjuvant-induced
arthritis in rats. Its anti-inflammatory activity in both test models was comparable to that of
acetyl salicylic acid. Bukittinggine also showed an inhibitory effect on the late proliferative
phase of the inflammatory process in cotton pellet-induced granuloma formation in rats. In
carrageenan-induced rat pleurisy, bukittinggine exhibited marked inhibitory activity on
exudate formation, accumulation of leukocytes and on PGE2-like activity in the exudate.[9]

Bukittinggine
8. Spilanthol: Isolated from Spilanthes acmella (Paracress), this alkaloid was studied for its
anti-inflammatory activity on murine RAW 264.7 macrophage by down-regulating LPSinduced(lipopolysaccharide-induced) inflammatory model. The result suggested that
spilanthol, attenuates the LPS-induced inflammatory responses in murine RAW 264.7
macrophages, partly due to the inactivation of nuclear factor kappa-light-chain-enhancer of
activated B cells(NF-kappaB), which negatively regulates the production of proinflammatory
mediators.[10]

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Spilanthol
9.Diaboline: This major alkaloid from Strychnos potatorum Linn was found responsible for
the antiarthitic activity. The extract of Strychnos potatorum Linn., seed at dose of 200 mg/kg,
p.o. showed reduction in the paw volume in Freunds adjuvant induced arthritic rats [11, 12].

Diaboline
10. Gentianaine: Isolated from Gentiana caucasa (Gentianaceae) leaves, it has shown low
anti-inflammatory activity in carrageenan-induced hind paw oedema [13].

Gentianaine
11. Gentianadine: This sesquiterpene alkaloid found in the aerial parts of Gentiana
turkestanorum, G. olgae, and G. olivieri (Gentianaceae) has shown anti-inflammatory and
muscle relaxant actions [13].

Gentianadine

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12. Gentianamine: Isolated from leaves of Gentiana olivieri and G. turkestanorum

(Gentianaceae), this alkaloid has shown anti-inflammatory activity in carrageenan-induced
hind paw oedema [13].

Gentianamine
13. Betonicine: The piperidine alkaloid isolated from Betonica officinalis, Marrubium
vulgare, Stachys sylvatica (Labiatae), Achillea moschata, and A. millefolium (Compositae)
has been found to significantly inhibit carrageenan-induced hind paw oedema [14].

Betonicine
14. Tylophorine: Isolated from leaves of Tylophora indica (Asclepiadaceae), this alkaloid
was shown to inhibit the primary and secondary responses of adjuvant-induced arthritis [15].

15. Tylophorine analog- DCB 3503: Isolated from Chinese herb Tylophora atrofolliculata,
it significantly suppresses the development and progression of collagen-induced arthritis
(CIA). Moreover, it completely blocks the LPS-triggered acceleration of joint inflammation
and destruction. Consistent with its effects in vivo, it significantly suppresses the synthesis of
pro-inflammatory cytokines in inflamed joints as well as cytokine synthesis by macrophages
examined ex vivo. DCB 3503 treatment also reduces the levels of inflammatory cytokines
(IL-6, IL-12, and TNF) produced by bone marrowderived dendritic cells in vitro. However,
it shows no direct effect on T cell proliferation and B cell antibody response [16].

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16. Trilobine and Isotrilobine: These two alkaloids from roots of Cocculos trilobus
(Menispermaceae) showed inhibitory effect against cotton pellet and adjuvant arthritis in rats
[17]

17. Hypaconitine: The betalain alkaloid from Aconitum collianthum, A. carnichaeli, and A.
Napellus (Ranunculaceae) showed significant inhibitory activity against carragenan-induced
oedema[18].

Hypaconitine
18. Piperine and piperidine (Piper nigrum Linn (Piperaceae): Black pepper increases the
secretion of gastric juices and also the bio-availability of certain drugs. Piperine when
administered orally at a dose level of 20 and 100 mg/kg/day for eight days caused decrease in
the arthritic symptoms in carrageenan induced acute paw arthritis[19, 20].

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Piperine

piperidine

19. Thalidasine: The bis-isoquinoline alkaloid obtained from the leaves of Thalictrum
dasycarpum (Ranunculaceae) (reported for its effect on rheumatic swelling of joints and
sprains) exhibited anti-inflammatory activity in carrageenan-induced hind paw oedema [21].

Thalidasine
20. Tinosporine, Tinosporidine, and Tinosporaside: These major alkaloids and other
constituents as Cordifolide, diterpene glycoside Cordifol, Heptacosanol, Clerodane furano
diterpene, Diterpenoid furanolactone, Columbin and -sitosterol have been isolated from
Tinospora cordifolia Linn. (Menispermaceae). The plant is used to improve the immune
system and the body's resistance to infections. The bitter principle present shows antiperiodic,
antispasmodic, anti-inflammatory and antipyretic properties. It is used in the treatment of
rheumatoid arthritis. At the dose of 100 mg/kg it showed reduction of paw volume in
collagen induced arthritic rats [22, 23].

Tinosporine

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heptacosanol

clerodane

furanolactone

FLAVONOIDS
21. Aromadendrin, Apigenin and Vitexin: Isolated from Justicia gendarussa linn
(Acanthaceae) these are used to treat inflammation and rheumatoid arthritis in folk medicine.
Its ethanolic extract showed significant anti-arthritic activity similar to that of aspirin against
Freunds adjuvant-induced and collagen-induced arthritic rat models [24, 25, 26].

Aromadendrin.

Apigenin

Vitexin
22. Baicalin, Baicalein and Wogonin: The flavonoids from leaves of Scutellaria baicalensis
Georgi (Labiatae) have been screened in comparison with three standard anti-inflammatory
agents viz phenylbutazone, indomethacin, and dexamethasone for activity in various
experimental models of inflammation. All the test substances were found to inhibit an
increase in vascular permeability in mice induced by acetic acid and reduce acute paw
oedema in rats. They also suppressed the secondary lesion in developing adjuvant-induced
arthritis in rats [27].

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Wogonin
23. Kolaflavanone: Isolated from the rind of Garcinia kola (Guttiferae), it Inhibited primary
and secondary responses of adjuvant induced arthritis in rats [28].

24. Rutin, Quercetin (Flavonols) and Hesperidin (Flavanone): The anti-inflammatory

activities of these flavonoids were investigated in rats using the Mizushima et als model of
acute and chronic inflammation. Intra-peritoneal administration of rutin, quercetin

and

hesperidin, given at daily doses (80 mg/kg) inhibited both acute and chronic phases of
inflammation. Rutin was the most active in the chronic phase. [29]

Qurecetin

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Hesperidin
25. Epiafzelechin: This flavonoid isolated from aerial parts of Celastrus orbiculatus
(Celastraceae) is an inhibitor of cyclo-oxygenase (COX-1) activity of prostaglandin H2
synthase. (-) Epiafzelechin exhibited about 3-fold weaker inhibitory potency on the enzyme
activity than indomethacin as a positive control. (-)Epiafzelechin exhibited significant antiinflammatory activity on carrageenan-induced mouse paw oedema, following (100mg/kg)
dose administrated orally 1 h prior to carrageenan treatment.[30]

Epiafzelechin
26. Chrysin,Oroxylene, Oroxylin-A, Scutellarin and Biochanin-A : These flavinoids from
Oroxylum indicum are responsible for the anti-inflammatory, anti-arthritic, and anti-bacterial
activities of this plant [31, 32].

Chrysin

Scutellarin

Baicalein
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27. 3-O-methylviolanone: Found in heartwood of Dalbergia odorifera T. Chen.

(Leguminosae) this is a traditional Chinese medicine known as jiangxiang which has been
used to treat blood disorders, ischemia, swelling, necrosis, and rheumatic pain. It has shown
significant anti-inflammatory activity [33].

3-O-methylviolanone
GLYCOSIDES
28. Robinin: The kaempferol glycoside isolated from Robinia pseudacacia leaves
(Leguminosae) has shown inhibition of

exudative and proliferative phases of the cotton

pellet granuloma (50 mg/kg/day p.o. in 7 days)[34]. It is also used as an anti-inflammatory and
anti-rheumatic agent in Spains folklore medicine.

Robinin
29. Stephanoside E and Stemucronatoside K: These steroidal glycosides from the roots
and stems of Stephanotis mucronata (Blanco) Merr.(Asclepiadaceae) are used for the
treatment of rheumatoid arthritis and rheumatic aches in Chinese folklore medicine [35] .

Stemucronatoside K

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30. Xanthorhamnin: Isolated from the seeds of Rhamnus infectoria (Rhamnaceae), it has
been patented as an anti-inflammatory agent and recommended for the treatment of
rheumatoid arthritis and for use in ophthalmology [36].

Xanthorhamnin
31. Stereospermin, Stereospermiside and Stereostin: Isolated from Stereospermum
kunthianum (Bignoniaceae), these are used to treat various ailments including inflammatory
conditions (rheumatoid arthritis) and pain. A study using different models of inflammation,
these flavinoids at dose levels of 20 mg/kg, (Stereostin, Stereospermin (p<0.0001) and
Stereospermiside(p<0.05) ) significantly increased the carrageenan-induced pain threshold
compared to the distilled water treated animals. Similarly, at the same doses the three
compounds significantly (p<0.0001) inhibited both phases of the formalin-induced pain with
a more pronounced effect on the second phase than in the first phase.[37]

Stereostin,

Stereospermin

32. Benzoxazinoid: isolated from the roots of Coix lachryma-jobi L. (Graminae.) It is

present in plants as glucoside. The roots of C. lachryma-jobi have been used in China for the
treatment of rheumatism and neuralgia.[38]

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Benzoxazinoid
33. Harpagoside: This iridoid glycoside from Harpagophytum procumbens has been used
for thousands of years in Africa for the treatment of fever, rheumatoid arthritis, and skin
conditions and is currently available as an alternative treatment for pain and osteoarthritis[39].
Harpagoside has been shown to suppress lipopolysaccharide-induced inducible nitric oxide
synthase and cyclooxygenase (COX)-2 expression through inhibition of nuclear factor-B
activation.[40]

Harpagoside
34. Salicin and Populin: These phenolic glycosides from Populus alba have been used for
polyarthritis and were part of Unguentum populi, an ointment used for gout and
rheumatism.[41]

Salicin

Populin

35. Cimigoside and 27-deoxyactein triterpene glycosides: These are found in the roots and
rhizomes of black cohosh (Actaea racemosa Linn. Family, Rununculaceae). The roots and
rhizomes are used in arthritis, dyspepsia, kidney problems, malaria, snake bite and as insect
repellent. These are used to decreases the inflammation produced due to the arthritis. Other

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chemical compounds extracted from the black cohosh, include acteina, salicylic acid, and an
isoflavone- formononetine.[42, 43, 44].

Cimigoside

27-deoxyactein

salicylic acid

formononetine

36. Asperuloside and deacetyl asperuloside: These two iridoid glycosides isolated from
Lasianthus acuminatissimus Merr are used for treatment of rheumatoid arthritis. Other iridoid
glucosidic dimmers present in the plant are nonglycosidic iridoid, paederoside, daphylloside,
citraside A, benzyl 6-o-a-L-rhamnopyranosyl - b-D-glucopyranoside.[45]

Asperuloside

Paederoside

Daphylloside

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37. Chiisanoside and chiisanogenin: These triterpenoid glycosides found in the leaves and
stem bark of Acanthopanax chiisanensis Nakai (Araliaceae) have been used as antirheumatic. To find the anti-inflammtory constituents of the herb leaves, phytochemical
isolation procedures were performed by activity-guided fractionation in carrageenan- and
Freund's complete adjuvant (FCA) reagent-induced rat models. The anti-inflammatory effects
of the two compounds were supported by the reduction of carrageenan-induced lipid
peroxidation and hydroxy radical in serum [46].

Chiisanoside

chiisanogenin

38. Anthraquinone, anthracene, cinnamic acid and anthranilic acid: The anthraquinone
glycosides found in Aloe Vera plants are responsible for the activity. The anti-arthritic
property of aloe vera is due to the anthraquinone compounds. these stimulate the immune
system and are powerful antinflammatory agents. Topical application of aloe vera extract
resulted in the reduction of inflammation and arthritis in adjuvant induced arthritis in Sprague
Dawley rats [47, 48, 49]

Anthraquinone,

anthracene,

cinnamic acid

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SAPONINS
39. Smilaxin, Prosapogenin A, Dioscin, Gracillin, Pseudoprotodioscin, Methygracillin
and Methylprotodioscin: These saponins found in the extract of Smilax sarsaparilla L. and
Smilax china L are used in traditional Saudi Arabian medicine for rheumatism, arthritis, gout
and other inammatory diseases. Smilax china L. is used for the treatment of rheumatoid
arthritis, gout and other inammatory ailments.[50].

Smilaxin,

Prosapogenin A

Dioscin,

Gracillin

Pseudoprotodioscin

Methylprotodioscin

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40. Momordin Ic (saponin) and oleanolic acid: Isolated from Kochia scoparia fruits, these
possess anti-rheumatoid activity. MeOH extract of Kochia scoparia was fractionated into
CHCl3-(chloroform), EtOAc-(ethyl acetate) and BuOH (butyl alcohol) extracts and the last
fraction were hydrolyzed by 3%-NaOH (MeOH-H2O) to compare the bioactivities on
antinociceptive and anti-inflammatory effects. Silica gel column chromatography of BuOH
fraction

afforded

large

amount

of

3-O-beta-D-xylopyranosyl

(1

3)-beta-D-

glucuronopyranosyl oleanolic acid (momordin lc) and that of acid hydrolysate of BuOH
fraction gave 3-O-beta-D-glucuronopyranosyl oleanolic acid (momordin lb), its 6'-O-methyl
ester and oleanolic acid. Silica gel column chromatography of alkaline hydrolysate afforded a
large amount of momordin lc. MeOH extract and both EtOAc- and BuOH fractions were
active in the rheumatoidal rat induced Freund's complete adjuvant reagent (FCA) whereas
CHCl3 fraction was inactive. Momordin lc and oleanolic acid showed significant activities in
the same assay but oleanolic acid 3-O-glucuronopyranoside showed no activity. These results
suggest that momordin lc and its aglycone, oleanolic acid, could be active principles for
rheumatoid arthritis. [51, 52].

Momordin Ic

oleanolic acid

41. Echinocystic acid: Isolated from leaves of Baccharis trimera (Asteraceae), it possesses
activity capable of preventing various chemically induced oedemas in rats and abdominal
writhing following acetic acid injection in mice[53]. This South American plant is used in
traditional medicine, internally, for the treatment of rheumatism, hepatobiliary disorders, and
diabetes.

Echinocystic acid

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42. Phytolaccoside B: This glucosidal saponin isolated from roots of Phytolacca americana
L. (Phytolaccaceae) exhibited anti-rheumatic and anti-inflammatory actions [54, 55].

Phytolaccoside B
TERPENOIDS AND STEROIDS
43. Boswellic acid : In India, the oleo-gum resin of Boswellia serrata Roxb. Ex Coleb
(Burseraceae) under trade name Sallaki is used for the treatment of rheumatism and
nervous diseases. It has been established that anti-inflammatory and antiarthritic activities are
due to the presence of boswellic acid and other related pentacyclic triterpene acids[56].

Boswellic acid
44. Germacrene

D,

(Z)--farnesene,

-caryophyllene,

-pinene,

-cadinene

(sesquiterpenes): Found in plant Teucrium Chamaedrys (Lamiaceae), these are responsible

for the biological activity of plant. The plant has been used as anti inflammatory, Antirheumatic, digestive and diuretic.[57, 58]

Germacrene D

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(Z)--farnesene

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-pinene

-cadinene

45. Hydroxyachillin: This sesquiterpene lactone from aerial parts of Tanacetum

microphyllum (Compositae) is used in the Iberian peninsula since ancient times and in
Spanish traditional medicine as an anti-inflammatory and anti-rheumatic agent, and for its
beneficial effects on the digestive tract. A study was carried out to investigate the effects of
hydroxyachillin on mouse ear oedema induced by PMA (phorbol myristate acetate).
Hydroxyachillin significantly (p0.01) inhibited ear swelling in a dose-dependent manner,
and was as effective as the reference drugs. The PMA-induced vascular permeability was
significantly (p0.05) reduced by hydroxyachillin at the highest dose (3 mg/ear).
Histologically, the signs of inflammation were greatly reduced in the hydroxyachillin-treated
ear lesions. the data suggests that hydroxyachillin is an effective anti-inflammatory agent in
this model, and that the inhibition of Protein kinase- C may be one of the mechanisms of
hydroxyachillin's effect.[59]

Hydroxyachillin
46. Mezerein, genkwadaphin, 1, 2-dehydrodaphnetoxin and daphnetin:

These

diterpenoids from various species of Daphne (Daphne tangutica, Daphne mezereum, Daphne
laureola L and Daphne oleoides Schreb) have been used traditionally for inammatory
complaints. These phytoconstituents were found to be responsible for anti-rheumatic
activity[60, 61].

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daphnetin

mezerein

47. Bartogenic acid (BA): This triterpene isolated from Barringtonia racemosa Linn
(Lecythidaceae) is responsible for anti rheumatic activity of this plant. It has anti-microbial,
anti-oxidant and anti-inflammatory activities, thus finds a use in rheumatoid arthritis. BA
protected rats against the primary and secondary arthritic lesions, and haematological
perturbations induced by Complete Freunds Adjuvant (CFA)[62, 63, 64].

bartogenic acid
48. Mannitol, beta-amyrin (triterpenoid), beta-sitosterol, benzoic acid and benzoic ester
of longanin, nycthanic acid: From Night jasmine (Ncytanthes arbortristis) Linn.
(Oleaceae), these are used for the treatment of rheumatoid arthritis. Its leaves inhibited the
acute inflammatory oedema produced by different phlogistic agents, viz. carrageenan,
formalin, histamine, 5-hydroxytryptamine and hyaluronidase in the hindpaw of rats. Acute
and chronic phases of formaldehyde induced arthritis were significantly inhibited. Nyctanthes
arbortristis Linn. Was also found to inhibit the inflammation produced by immunological
methods, viz. Freund's adjuvant arthritis[65].

Mannitol

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beta-amyrin

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COUMARINS
49. Osthol: Isolated from Cnidium monnieri, it has been reported to exhibit various
biological activities. Study to demonstrate its anti-inflammatory activity showed that osthol
inhibited TNF- (Tumor necrosis factor alpha), NO and COX-2 expression in LPS
(lipopolysaccharide)-stimulated macrophages, without reducing the expression of IL-6.
Furthermore, the phosphorylation of p38-JNK1/2 (c-Jun N-terminal kinase1/2), PKC-
(protein kinase C) and PKC- induced by LPS Was inhibited by osthole; however, the
phosphorylation of ERK1/2 (extracellular signal regulated kinase 1/2) and PKC- was not
reduced by osthole. Osthole also inhibited NF-B activation and ROS release in LPSstimulated macrophages. The results indicate that osthole is the major anti-inflammatory
ingredient in Cnidium monnieri seed[66].

Osthol
50. Chromones: The isomers of coumarin derivatives of benzopyran with a substituted keto
group on the pyran ring, these are present in number of plants like 6,7-dimethoxy-2,3dihydrochromone isolated from Sarcolobus globosus. Eucryphin (chromone rhamnoside)
isolated from the bark of Eucryphia cordifolia and Chromone 3-[2-(3, 5-dimethoxy
phenyl)ethyl 1]-2-methyl from Erucaria microcarpa. Latter has been proved as a scavenger
for DPPH (2,2-diphenyl-1-picrylhydrazyl) free radical. Free radicals have been proposed to
induce cellular damage which may play a role in rheumatoid arthritis, inflammatory disorders
as well as aging process[67, 68].

Chromones

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XANTHONES
51. Dehydrocycloguandin: The xanthone derivative isolated from Calophyllum brasiliense
and C. inophyllum leaves (Guttiferae) demonstrated anti-inflammatory activity on the
exudative and proliferative phases of cotton pellet granuloma, formaldehyde-induced
arthritis, and carrageenan oedema[69].

Dehydrocycloguandin
52. Mangiferin and isomangiferin: These xanthone derivatives from the leaves and bark of
Mangifera indica Linn. (Anacardiaceae) showed strong antioxidant effect. The methanolic
extract of Mangifera indica possessed anti inflammatory activity which is shown by the
arthritic parameters like arthritic index, paw oedema and rheumatoid factor[70, 71, 72].

mangiferin,

isomangiferin

TANNINS
53. Chebulinic acid (ellagitannin): isolated from terminalia chebula retz, it is used in
chronic ulcer, leucorrhoea and fungal infections of skin. It is also used as neuroprotective and
antioxidant. Hydro-alcoholic extract of this plant showed anti-arthritic activity in
formaldehyde or complete Freund's adjuvant induced arthritis. The anti-arthritic activity of
Terminalia chebula Retz.,is thought to be due to its modulatory effect on proinflammatory
cytokine expression in the synovium [73, 74, 75].

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World Journal of Pharmacy and Pharmaceutical Sciences

chebulinic acid
PEPTIDES, CATECHINS AND FATTY ACIDS
54. Aurantiamide acetate (dipeptide) and 1, 3-Dibenzyl Urea:

Isolated from roots of

Moringa oleifera, these were found to be anti-inflammatory/ Anti-arthritic and analgesic.

Aurantiamide acetate showed significant inhibition on TNF- and IL-2 but not on IL-6.
While 1, 3-dibenzyl Urea, showed significant analgesic activity in dose dependant manner
and significant inhibition on IL-2. These results indicate that these compounds may be
responsible for the anti-inflammatory/ antiarthritic and analgesic activity.[76]

Aurantiamide acetate

1, 3-Dibenzyl Urea

55. Epigallocatechin: It is a catechin found in Camellia sinensis Linn. (Theaceae). Other

constituents are caffeine and essential oils. The most important in Green Tea (-)
epigallocatechin is a potent antioxidant. The reduced collagen induced arthritis incidence and
severity was reflected in a marked inhibition of the inflammatory mediators COX-2, IFN,
and TNF in arthritic joints of green tea-fed mice. Total immunoglobulins (IgG) and type II
collagen-specific IgG levels were found to be lower in serum in arthritic joints of green teafed mice [77, 78].

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Epigallocatechin
56. Eicosapentenoic acid: An omega-3 fatty acid, found to be of great medicinal value
because of its importance in curing coronary heart disease, asthma, high blood pressure and
inflammatory disorders as rheumatoid arthritis. The components isolated from Heliotropium
indicum have different medicinal values which compare very well with the traditional uses of
the plant. For example, it also cures Rheumatoid Arthritis, menstrual problems and wound
healing by preventing blood from clotting, reduces pain and swellings. This acid is sufficient
to sterilize wounds and keep them off from other microbes which may not strive under harsh
acidic medium.[79]

Eicosapentenoic acid
ORGANIC COMPOUNDS: Myristicin: It is a phenylpropene, a natural organic compound,
found in various plants like nutmeg, parsley and dill. A study was carried out to find the antiinflammatory

effect

of

myristicin

on

double-stranded

RNA

(dsRNA)-stimulated

macrophages. Myristicin did not reduce the cell viability of RAW 264.7 mouse macrophages
at concentrations of up to 50M. Myristicin significantly inhibited the production of calcium,
nitric oxide (NO), interleukin (IL)-6, IL-10, interferon inducible protein-10, monocyte
chemotactic protein (MCP)-1, MCP-3, granulocyte-macrophage colony-stimulating factor,
macrophage inflammatory protein (MIP)-1, MIP-1, and leukemia inhibitory factor in
dsRNA [polyinosinic-polycytidylic acid]-induced RAW 264.7 cells (P < 0.05). In conclusion,
myristicin has anti-inflammatory properties related with its inhibition of NO, cytokines,
chemokines, and growth factors in dsRNA-stimulated macrophages via the calcium
pathway[80].

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Myristicin
MISCELLANEOUS: Uncaria tomentosa (Rubiaceae) contains several alkaloids, steroids,
terpenoids, flavonoids and tannins that are responsible for its medical effects. These are
Ajmalicine, akuammigine,

corynantheine, corynoxeine, iso-pteropodine, pteropodine,

speciophylline, rhyn chophylline (alkaloids), campesterol, sitosterols, stigmasterol,

strictosidines. daucosterol (anabolic steroid), chlorogenic acid, hirsuteine, hirsutine, loganic
acid, lyaloside, mitraphylline, oleanolic acid, (terpenoids), rutin, procyanidins , cinchonain
(flavonoids), catechin, epicatechin, palmitoleic acid (fatty acid) and quinovic acid,
(glycosides). It is used as anti-inflammatory, anti-arthritic, anti-oxidant, anti-diabetic, and in
chronic fatigue disease. Animal study of anti-inflammatory activity of cats claw extract
showed its ability to reduced paw oedema in carrageenan induced inflammation rat model[81,
82, 83]

Akuammigine

campesterol

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Catechin

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297

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World Journal of Pharmacy and Pharmaceutical Sciences

chlorogenic acid

cinchonain

corynantheine

corynoxeine

Daucosterol

epicatechin

hirsuteine

hirsutine

iso-pteropodine

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loganic acid

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298

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World Journal of Pharmacy and Pharmaceutical Sciences

Lyaloside

mitraphylline

palmitoleic acid

procyanidins

quinovic acid

sitosterols

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pteropodine

rhynchophylline

speciophylline

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rutin

stigmasterol

299

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World Journal of Pharmacy and Pharmaceutical Sciences

Strictosidines
Table1: Summarises various antirheumatic phytoconstituents and their plant sources.
Sr. No. Chemical Constituent
ALKALOIDS

Plant Source

Reference
Ferrante et.al, 1990.
Teh BS et.al, 1990.
Ivanovska and Philipov
1996.

1.

Tetrandrine

Stephania tetrandra
Menispermaceae

2.

Berbamine

Berberis vulgaris

3.

Sinomenine

4.

Stachydrine

5.

Colchicine

6.

Aconitine

7.

Bukittinggine.

8.

Spilanthol

Spilanthes acmella

9.

diaboline

Strychnos potatorum
Linn., (Loganiaceae)

10.

Gentianaine

11.

Gentianadine

12.

Gentianamine

13.

Betonicine

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Sinomenium acutum
Menispermaceae
Capparis spinosa L.
Capparidaceae
corns and seeds of
crocus like plants
Aconitum genus
Sapium baccatum
Roxb.
(Euphorbiaceae)

Gentiana caucasa
(Gentianaceae)
Gentiana
turkestanorum,
G. olgae, and
G. olivieri
(Gentianaceae).
Gentiana olivieri and
G. turkestanorum
(Gentianaceae).
Betonica officinalis,
Marrubium vulgare,
Stachys sylvatica
(Labiatae),
Achillea moschata, and
A. millefolium
(Compositae).

Vol 3, Issue 11, 2014.

H. Feng et.al, 2007.

1.Feng X et.al, 2011.
Sais G et.al, 1995.
Malkinson FD 1982.
1.Shi H et.al, 1990.
Panthong A et.al, 1998.
Wu LC et.al, 2008.
Ekambaram S et.al 2010.
Narendhirakannan RT
et.al, 2007.
Benn and Jacyno, 1983.

Benn and Jacyno, 1983.

Benn and Jacyno, 1983.

Lombardino, 1985.

300

Ghulam et al.

World Journal of Pharmacy and Pharmaceutical Sciences

14.

Tylophorine analog, DCB

3503

15.

Tylophorine

16.

Trilobine
Isotrilobine

17.

Hypaconitine

18.

piperine, piperidine

19.

Thalidasine

20.

tinosporine, tinosporide,
tinosporaside,

21.
22.

FLAVONOIDS
aromadendrin.
Apigenin,
vitexin
Baicalin, Baicalein
Wogonin

23.

Kolaflavanone

24.

Rutin,
Quercetin (Flavonols)
Hesperidin (Flavanone):

25.

Epiafzelechin

26.

27.

chrysin,
oroxylene,
oroxylin-a,
scutellarin
baicalein,
biochanin-a and
ellagic acid
57. 3-O-methylviolanone.

Tylophora
atrofolliculata
Tylophora indica
Asclepiadaceae
Cocculos trilobus
Menispermaceae
Aconitum collianthum,
A. carnichaeli, and A.
Napellus
(Ranunculaceae).
Piper nigrum Linn
(Piperaceae)
Thalictrum
dasycarpum
Ranunculaceae
Tinospora cordifolia
Linn.
(Menispermaceae)

Xin You et.al, 2006.

Handa et.al, 1992.
Johji et.al, 1975.

Djerassi et.al.1994.
Bang et.al 2009.
pradhan et.al 2009.
Phillipson et.al,1985.
Singh SS et.al, 2003.
Paval J et.al 2009.

Paval J et.al 2011.

Bachheti RK et.al, 2011.
Paval J et.al 2009.

Justicia gendarussa
Linn., (Acanthaceae)
Scutellaria baicalensis
Labiatae
Garcinia kola
Guttiferae.

Kubo et.al, 1984.

Saini and Ghosal 1984.
Teresita Guardia et.al,
2001.

Celastrus orbiculatus
2. Min et.al, 1999.
Celastraceae

Oroxylum indicum

1. Chen et.al 2003.

2. Maitreyi et.al, 2008.

Dalbergia odorifera
Leguminosae

Chan et.al, 1998.

GLYCOSIDES
28.

Robinin

29.

stephanoside E,
Stemucronatoside K

30.

Xanthorhamnin

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Robinia pseudacacia
Borja
Leguminosae
Stephanotis mucronata
(Asclepiadaceae)
Rhamnus infectoria
Rhamnaceae

Vol 3, Issue 11, 2014.

Cabor M 1979.
Xiao-yu Li et.al 2012.
Harbone and Mabry
1975.

301

Ghulam et al.

31.

Stereostin,
Stereospermin
Stereospermiside

32.

Benzoxazinoid

33.

Harpagoside

34.

Salicin
Populin

35.

World Journal of Pharmacy and Pharmaceutical Sciences

cimigoside,

Stereospermum
3. Ching et.al, 2009.
kunthianum
(Bignoniaceae)
Coix lachryma-jobi
Tang et.al, 1984.
(Graminae)
Harpagophytum
McGregor G et.al, 2005.
procumbens
Huang TH-W et.al, 2006.
Populus alba

Hiller et.al, 2006.

Paiboon Nuntanakorn
Actaea racemosa Linn. Black 2004.
(Ranunculaceae)
Johnson LP 2002.
Setty AR 2005.

36.

Asperuloside,
Asperuloside,
Paederoside,
Daphylloside,

Lasianthus
acuminatissimus Merr

Katyayani et.al, 2010.

37.

Chiisanoside
chiisanogenin

Acanthopanax
chiisanensis Nakai
(Araliaceae)

Hahn et.al, 1984.

38.

39.

40.

Anthraquinone,
anthracene,
cinnamic acid
anthranilic acid
SAPONINS
Smilaxin,
Prosapogenin a,
Dioscin,
Gracillin,
Pseudoprotodioscin,
Methygracillin
Methylprotodioscin
Momordin Ic and its
aglycone, oleanolic acid,
Cucurbitane

41.

Echinocystic acid

42.

Phytolaccoside B

Aloe barbadensis
(Liliaceae)

Smilax sarsaparilla L

Sashida et.al, 1992.

Kochia scoparia

Biswas et.al, 1991.

Choi J et.al, 2002.

Baccharis trimera
(Asteraceae)
Phytolacca americana
L.
Phytolaccaceae

43.
TERPENOIDS AND STEROIDS
43.
Boswellic acid
Boswellia serrata
Germacrene D,
(Z)--farnesene,
Teucrium Chamaedrys
44.
-caryophyllene,
Lamiaceae
-pinene,
-cadinene
45.
Hydroxyachillin
Tanacetum microphyllum

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4. Joshph and Raj 2010.

5. Devis RH et.al, 1986.
6. Aggarwal & Paridhavi
2009.

Vol 3, Issue 11, 2014.

Gene et.al, 1996.

Woo and Kang 1976.
Chi and Kim 1985.

Dr.Amrit Pal 2005.

R. Chiej 1984.
Koster et.al, 1959.
A. M. Silvn et.al, 1996.

302

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World Journal of Pharmacy and Pharmaceutical Sciences

Compositae

46.

47.

48.

genkwadaphin
1,258. Daphne tangutica
dehydrodaphnetoxin 59. Daphne mezereum
daphnetin
60. Daphne laureola
mezerein
bartogenic acid
mannitol, -amyrin,
-sitosterol,
benzoic acid and
benzoic ester of
longanin,
nycthanic acid

Jaric et.al, 2007.

Yesilada et.al, 2001.

Barringtonia racemosa Linn

( Lecythidaceae)

Ncytanthes arbortristis Linn.

(Oleaceaeis)

Behbahani M et.al 2007.

Patil KR et.al 2011.
Mayo JL et.al. 1998.

Sandhar HK et.al, 2011.

COUMARINS
49.

Osthol

Cnidium monnieri

50.

Chromones

Erucaria microcarpa

Pei-Chun Liao et.al,

2010.
Hashem 2000-2001.
1. R. Tschesche et.al 1979.

XANTHONES
51.

Dehydrocycloguandin

Calophyllum brasiliense
C. inophyllum (Guttiferae)

52.

mangiferin,
isomangiferin,
tannin and gallic acid

Mangifera indica Linn.

(Anacardiaceae)

53.

54.
55.
56.
57.

TANNINS
Chebulinic acid,
Gallic acid,
anthraquinone
sinnosides

Terminalia chebula Retz

PEPTIDES, CATECHINS AND FATTY ACIDS

Aurantiamide acetate
Moringa oleifera
1, 3-Dibenzyl Urea
Epigallocatechin
Camellia sinensis
caffeine and
Linn. (Theaceae)
essential oils
Eicosapentenoic acid
Heliotropium indicum
ORGANIC COMPOUND
Myristica fragrans Houtt
Myristicin
Myristacaceae
MACELLINIOUS

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Vol 3, Issue 11, 2014.

Hostettmann, K. and
Hostettmann, M. (1989).
Garrido et.al 2001.
Garrido et.al 2004.
Sun HY et.al 2006.

Nair V et.al, 2010.

Singh and Sharma 2010.
Rajendran R 2010.

Koneni et.al, 2009.

Akroum S et.al, 2009.
Chopade VV et.al. 2008.
Shoge et.al 2011.
Ji Young and Wansu
2011.

303

Ghulam et al.

58.

Ajmalicine,
akuammigine,
corynantheine,
corynoxeine, isopteropodine,
pteropodine,
speciophylline, rhyn
chophylline
(alkaloids),
campesterol,
sitosterols,
stigmasterol,
strictosidines.
daucosterol
(anabolic steroid),
chlorogenic acid,
hirsuteine,
hirsutine, loganic
acid, lyaloside,
mitraphylline,
oleanolic acid,
(terpenoids), rutin,
procyanidins ,
cinchonain
(flavonoids),
catechin,
epicatechin,
palmitoleic acid
(fatty acid)
and quinovic acid,
(glycosides).

World Journal of Pharmacy and Pharmaceutical Sciences

7. Jean Bruneton.
8. Cat'sClaw,http://fastflusto
p.
Uncaria tomentosa (Rubiaceae)
9. com/Cats Claw.html(as
viewed on 14/2/12).
10. Ahmed 2010.

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