Potential Anti-Arthritic Agents From Indian Medicinal Plants | Open Access Journals

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Potential Anti-Arthritic Agents From Indian Medicinal Plants

Samrat Chauhan, Lalit Kishore, Navpreet Kaur and Randhir Singh*

M.M.College of Pharmacy, Maharishi Markandeshwar University, Mullana, Ambala, Haryana, India-133207

*Corresponding Author:
Randhir Singh
M.M. College of Pharmacy
Maharishi Markandeshwar University
Mullana, Ambala, Haryana, India-133207
Tel: 91-9896029234
E-mail: randhirsingh.dahiya@gmail.com

Received: 13/07/2015 Accepted: 20/08/2015 Published: 28/08/2015

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Abstract

Traditional medicines are used globally for management of rheumatoid arthritis since prehistoric times. This review emphasizes on the Indian medicinal flora and their traditional utilization in the management of rheumatoid arthritis. Peer reviewed articles from the last three decades and the classical textbooks were examined for bibliographic investigation. Plant extract traditionally used for ameliorating arthritic condition have been studied in the present review. 124 plants, traditionally used in the management of arthritis have been recorded. This study reflects the need to explore potential chemical moieties from unexploited plants in arthritic management along with the mechanism of action through which they would act, remain to be studied

Keywords

Anti-arthritic activity, Chemical moieties medicinal plants

Introduction

Rheumatoid arthritis (RA) is a chronic, progressive, and systemic inflammatory disorder. It preferentially affects the synovial membranes of joints and eventually leads to bone and cartilage destruction. RA affects 0.5%–1% of the adult population worldwide; the disease targets patients from every ethnic background and predominately females (2- or 3-fold more often than males). Although RA can occur at any age, it is more frequent among individuals in the fourth to sixth decades of life [1]. As a chronic disease which causes irreversible joint damage, RA exacts high costs from both the patients and society at large. The clinical manifestations of RA can be classified as articular and extra-articular. RA is indicated by fever, asthenia, fatigue, myalgia, and weight loss which appear before or concomitantly with the onset of the articular manifestations like synovial thickening, erythema, warmth and decreased mobility.

Pathophysiology

RA is associated with several genetic and environmental factors that contribute the phenotype in different combinations (Figure 1). RA is initiated by immune complexes and complement system, perpetuated by cytokines, and affected by metalloproteinases [2]. Antigen-activated CD4+ T cells stimulate monocytes, macrophages, and synovial fibroblasts which in turn lead to the production of cytokines interleukin-1, interleukin-6, and TNFa and secretion of matrix metalloproteinases through cell-surface signalling [3]. In early RA, large amount of neutrophils are present in synovial fluid [4]. Chronically, hypertrophy and hyperplasia forms projections into the joint capsule. Immune complexes found in the synovial fluid often are IgG/anti-IgG antigen-antibody complex [5]. In RA bone erosions caused by osteoclasts and proteolytic enzymes causes cartilage dissolution [6]. Rheumatoid factors (IgM & IgA) are key pathogenic markers [7].

pharmaceutical-sciences-Possible-molecular-mechanism-arthritis

Figure 1: Possible molecular mechanism for arthritis

Material and Methods

In this review, bibliographic investigation was done to retrieve articles available in the worldwide scientific databases viz. SCOPUS, PUBMED, SCIELO, NISCAIR and Google Scholar. Botanical names of plants were verified from International Plant Names Index, 2014 and the plant list, 2014. The inclusion criteria for the selection of plants includes (i) medicinal herbs with reported animal studies in management of arthritis, (ii) compounds isolated from medicinal plants with attributed potential in relieving arthritis and (iii) we limited studies to those published in the English language.

Results

One hundred and twenty four plants were reviewed from classical text books for their traditional use in rheumatoid arthritis (Table 1).

S.No. Name Family Common name Part used Disease References
1. Acacia polyantha Mimosaceae Svetakhair, kadarah Heartwood Rheumatism AryaVaidyaSala[19]
2. Achilleamillefolium Linn. Compositae Gandana Plant Rheumatism Kritikar KR[8]
3. Adenantherapavonina Linn. Mimosaceae Barigumchi, raktachandana Leaves Chronic rheumatism, gout
4. AlangiumlamarkiiThwaites. Alangiaceae Akhaul, akola Leaves Rheumatic pains
5. Alangium salviifolium Wang Alangiaceae Angol, dhera Roots Rheumatism AryaVaidyaSala[19]
6. Alpiniagalanga(L.) Willd. Zingiberaceae Kulanajn Rhizomes Rheumatoid arthritis
7. ApiumgraveolensLinn. Umbelliferae Ajmud, boriajmud Seeds Rheumatism Kritikar KR[8]
8. AzimatetracanthaLam. Salvadoraceae Kantagurkamai Root bark, leaves Rheumatism
9. BassialatifoliaRoxb. Sapotaceae Mahua, janglimohva Bark Rheumatism
10 BassialongifoliaLinn. Sapotaceae Mahua, moha Bark Rheumatism
11. CaesalpiniasappanLinn. Caesalpiniaceae Bakam, patang, tairi Wood Rheumatism
12. CarthamustinctoriusLinn. Compositae Barre, kussum Seeds oil Pain in joints, rheumatism
13. Cassia fistula Linn. Caesalpiniaceae Amaltas, girmala Leaves and fruits Rheumatism
14. Cassia fistula Linn. Caesalpiniaceae Amaltas, girmal Fruits Rheumatism AryaVaidyaSala [20]
15. CichoriumintybusLinn. Compositae Kasni Root Inflammation and pain in joints
16. Cinchona officinalisLinn. Rubiaceae Kunain Bark Arthralgia
17. CirhoriumintybusLinn. Asteraceae Kasni Whole plant Arthralgia
18. Citrulluscolocynthis(L.) Schrad. Cucurbitaceae Badi- indrayan, makkal Roots Rheumatalgia AryaVaidyaSala[20]
19. Commiphoramyrrha (nees)Engl. Burseraceae Bol, hirabol Gum Rheumatoid arthritis
20. Commiphorawightii (arn.)Bhandari Burseraceae Hill-mango Leaves Rheumatalgia
21. Corallocarpus epigeous (Rottler) Hook.f. Cucurbitaceae Akasgaddah, rakasgaddah Plant Rheumatism Kritikar KR[8]
22. CordiadichotomaG.Forst. Boraginaceae Lasura, lasora Fruits Arthralalgia
23. CotulaanthemoidesLour. Compositae Babuna, babunah Plant oil Rheumatism
24. Dasticacannabina Linn. Datiscaceae Akalbir, bhangjala Root Rheumatism
25. Delonixelanta(L.) Gamble Caesalpiniaceae Tiger bean, sankasura Plant Rheumatism
26. DichrostachyscinereaLinn. Mimosaceae Vurttulli, kheri Roots Arthralagia
27. DichrostachyscinereaWight &Arn. Mimosaceae Kheri, vartuli Root Rheumatism
28. DiospyroscandolleanaWight Ebenaceae Kari, karikkattai Bark Rheumatism
29. DiospyrospaniculataDalzell Ebenaceae Karivella, karunduvarai Bark Rheumatism
30. Drynariaquercifolia(Linn.) Polypodiaceae Asvakatri, katikapan Rhizomes Arthralagia AryaVaidyaSala[20]
31. Echinopsechinatus Compositae Gokhru, utakanta Plant Pain in joints
32. EphorbiaantiquorumLinn. Euphorbiaceae Tidhara Juice Rheumatism
33. Eugenia operculataRoxb. Myrtaceae Dugdugia, jamawa Fruit Rheumatism Kritikar KR[8]
34. Eugenia spicataLam. Myrtaceae Puvala, bhedas Plant Rheumatism
35. Euphorbia ligulariaRoxb. Euphorbiaceae Sehund, thuhar Whole plant Rheumatism
36. Ferula narthexBoiss. Umbelliferae Hing, hingra Stem, leaves Rherumatism
37. FicusbenghalensisLinn. Moraceae Bat, bargad Aerial root, bark, leaves, buds, fruits, latex Antiarthritic AryaVaidyaSala [21] Kritikar KR[8] AryaVaidyaSala [21] Kritikar KR[8]
38. Flacourtiajangomasrausch. Flacourtiaceae Paniyala, paniyamalak Fruits Rheumatism
39. FritillariaroyleiHook. F. Liliaceae Kakoli Bulbs Rheumatalgia
40. Glycosmisarborea(Roxb.)Dc. Rutaceae Girgiti,potali Whole plant Rheumatism
41. GossypiumherbaceumLinn. Malvaceae Kapas, ruyi Leaves Rheumatoid arthritis
42. Grangeamaderaspatana(L.) Poir. Compositae Mukhatari, mustaru Root Rheumatism
43. HeliotropiumindicumnLinn. Boraginaceae Siriyari, hattasura Whole plant Rheumatism
44. Hemidesmusindicus(Linn.) R.br. Asclepiadaceae Anantamul, magrabu Roots Arthralgia
45. Hiptagebenghalensis(Linn.) Kurz Malpighiaceae Madhavilata, madhumalati Bark, leaves, flowers Rheumatism
46. HolarrhenapubescensWall. ex G.Don Apocynaceae Kurci, kuda Bark, seeds Rheumatism
47. Holoptelaintegrifolia(Roxb.) Planch. Ulmaceae Cilbil, kanju Bark, leaves Rheumatism
48. HyoscyamusnigerLinn. Solanaceae Khurasaniajavayan, khurassanijamani Leaves, seeds Rheumatoid arthritis
49. IlliciumverumHook. F. Magnoliaceae Anasphal Fruits Rheumarthritis
50 . InularacemosaHook. F. Asteraceae Pohakarmul, puskarmul Roots Arthralgia
51. Ipomoea nil (Linn.) Roth Convolvulaceae Kaladana, jharmaric Seeds Arthralgia
52. JasminumgrandiflorumLinn. Oleaceae Chambeli Root Rheumatism
53. Jasminummultiflorum(Burm.f.) Andr. Oleaceae Kundphul Flowers Rheumatism
54. JatrophacurcasLinn. Euphorbiaceae Jungle erand, paharierand Seeds (oil) Rheumatism
55. JuglansregiaLinn. Var. Kumaonia dc. Juglandaceae Akhor, akhrot Fruits Rheumatism
56. JusticiagendarussaBurm.f. Acanthaceae Nilinirgundi, udisambhalu Roots, leaves Rheumatism
57. Kaempferia galangal Linn. Zingiberaceae Candramula Rhizomes, root-stock, leaves Rheumatism
58. Lantana camaraLinn. Var. Aculeate (Linn.)Moldenke Verbenaceae Caturang, ghaneri Fruits Rheumatism
59. Launaeapinnatifida Compositae Bankau Plant juice Rheumatism
60. Lawsoniainermis Linn. Lythraceae Mehanti, hena Leaves Rheumatalgia
61. Leucasaspera(Willd.) Link Lamiaceae Chotahalkkusa Leaves, flowers Arthralgia
62. LiliumpolyphyllumD.Don Liliaceae Ksirakakoli Bulb Rheumatalgia
63. Madhucalongifolia(Koenig) Macbride Sapotaceae Mahva, mohva Seed (oil) Rheumatism
64. MangiferaindicaLinn. Anacardiaceae Aam, aamb Roots, bark Rheumatism
65. Matricaria chamomilla Linn. Compositae Babuna Oil Rheumatism Kritikar KR[8]
66. MelaleucaleucadendronLinn. Myrtaceae Kayaputi Plant oil Rheumatism
67. Mimosa pudicaLinn. Mimosaceae Lajjavanti, lajvanti Whole plant Rheumatism Kritikar KR[8] AryaVaidyaSala[22]
68. MomordicacharantiaLinn. Cucurbitaceae Karela, kareli Fruit Rheumatalgia
69. Momordicacochinchinensis Cucurbitaceae Gangerua, kathaamala Root Rheumatism
70. MyrtuscommunisLinn. Myrtaceae Murad, vilayatimehndi Fruit Rheumatism
71. MyxopyrumserratulumaW.Hill Oleaceae Pilacameli Leaves Rheumatism
72. Naraveliazeylanica(Linn.) Ranunculaceae Needamalli Whole plant Rheumatalgia
73. Nilgirianthus ciliates (Nees) Bremek. Acanthaceae Karvi, kara Roots Rheumatalgia
74. Nyctanthes arbor-tristisLinn. Oleaceae Har, harsinghar Leaves Rheumatism
75. OcimumbasilicumLinn. Lamiaceae Babul, babuyitulsi Whole plant Arthralgia, rheumatoid arthritis
76. OleacuspidataWall. &G.Don Oleaceae Kahu, kau Root Rheumatism
77. Operculinaturpethum(Linn.) Silva manso Convolvulaceae Nisoth, tarbut Roots Arthralgia
78. PaederiafoetidaLinn. Rubiaceae Bakuchi, somraj Whole plant Rheumatism
79. Pavettaindica Linn. Rubiaceae Kankra, papari Wood Rheumatism
80. Piper betleLinn. Piperaceae Pan, tambuli Whole plant Rheumatism
81. Piper cubeba Linn.f. Piperaceae Kababcini Dreid unripe berries Rheumatism
82. Piper nigrumLinn. Piperaceae Kalimirc, mirc Fruits Arthritis
83. PlumbagoroseaLinn. Plumbaginaceae Chitra,lalchita Root Rheumatic affections
84. PlumbagozeylanicaLinn. Plumbaginaceae Chita, chitarak Root Rheumatism
85. Plumieriaacutifolia Apocynaceae Chameli, gulachin Root bark Rheumatic pain
86. PremnacorymbosaRottl. Verbenaceae Arni, ageta Leaves Rheumatalgia
87. PrinsepiautilisRoyle Rosaceae Bekkra, bhekal Shrub oil Rheumatism
88. ProsopisspicigeraL. Mimosaceae Chhikura, safedkikara Bark Rheumatism
89. PsidiumguyavaLinn. Myrtaceae Amrud, amrut Leaves Rheumatism
90. PterocarpusmarsupiumRoxb. Fabaceae Bijasal, vijayasar Heartwood Rheumatoid arthritis
91. PuerariatuberosaDC. Fabaceae Vidarikand, sural Roots Arthritis
92. Randiadumetorum Rubiaceae Arar, mainphal Fruit Rheumatism
93. Rhazyastricta Apocynaceae Sundwar Roots, stem, leaves, flowers Chronic rheumatsim
94. Rhododendron campanulatum Ericaceae Cherailu, chimul Leaves Chronic rheumatism
95. RicinuscommunisLinn. Euphorbiaceae Erandi, erand Leaves Rheumatoid arthritis, arthralgia
96. Rosa alba Linn. Rosaceae Gulab Flower Rheumatism
97. RubiacordifoliaLinn. Rubiaceae Mamjith, majith Roots Rheumatoid arthritis
98. RutachalepensisLinn. Rutaceae Pismaram, sadab, satari Leaves Rheumatalgia Kritikar [8]
AryaVaidyaSala [23]
99. Salvadoraoleoides Salvadoraceae Bahapilu, jhalawan Seeds(oil) Painful rheumatic affections
100. Salvadorapersica Linn. Salvadoraceae Badapilu, jal Leaves Rheumatism
101. Sarcocephalusmissionis Rubiaceae Attuvanni, attuvanji Bark Rheumatism
102. Saussuraelappa Compositae Kot, pachak Root Rheumatism
103. Schleicheraoleosa(Lour.) Oken Sapindaceae Kusum, kausum Bark Arthralgia
104. SemecarpusanacardiumLinn.f. Anacardiaceae Bhela, bhilva Fruits Antiarthritic
105. Sesbaniagrandiflora(Linn.) Poir. Fabaceae Hathya, agast, basna Root-bark Arthralgia AryaVaidyaSala [23]
106. Setariaitalica(Linn.) P.beauv Poaceae Kamguni, Grains Rheumatism
107. Sidacordata(Burm.f.) Borssum Malvaceae Bananiyar, bhyunli Roots Arthritis
108. SidarhombifoliaLinn. Malvaceae Janglimedhi Roots, leaves Rheumatism, arthritis
109. SolanumsurattenseBurm.f. Solanaceae Rengani, kateli, kattay Whole plant Rheumatoid arthritis
110. Spilanthesacmella Compositae Akarkarha, pokormul Leaves Rheumatism Kritikar [8]
111. Stereospermumcolais Bignoniaceae Paraal, paatar, paadrii Leaves Rheumatalgia AryaVaidyaSala [23]
112. Symplocoscochinchinensis(Lour.) Moore Symplocaceae Bholiya, sodh Bark Arthritis
113. Tabernaemontanadivaricata(Linn.) Apocynaceae Chandni Roots Arthralgia
114. Trachyspermumroxburghianum(DC.) Craib Apiaceae Ajmud, randhuni Fruits Rheumatoid arthritis
115. TribulusterrestrisLinn. Zygophyllaceae Gokharu Whole plant Rheumarthritis
116. Trichodesmaindicum(Linn.)R.br. Boraginaceae Andhahuli, chotta-kulpha Whole plant Arthralgia
117. Trichosanthespalmata Cucurbitaceae Indrayanmahakal Fruit Rheumatism Kritikar KR[8]
118. Valerianawallichii Valerianaceae Barhana, chakra Root Pain in joints
119. VateriaindicaLinn. Dipterocarpaceae Saphed dammar, kahruba Seeds(oil) Rheumatism AryaVaidyaSala[23]
  VitexnegundoLinn. Verbenaceae Samhalu, saubhalu, nirgandi Roots Arthritis
120. VitextrifoliaLinn. Verbenaceae Saphed-samhalu, pani-ki-samhalu Leaves Arthralgia
121. VitisviniferaLinn. Vitaceae Dakh, drakh Stem(ash) Arthralgia
122. Xyliadolabriformis Mimosaceae Jambu Seeds Rheumatism Kritikar KR[8]

Table 1 Plants ith raditional/folkloric use in arthritis

Out of 124 traditional plants Forty-four articles were used for citing the proved anti-inflammatory and anti-arthritic activity in laboratory animals (Table 2).

S. No. Plant name Family Parts of plant used Active constituents Dose, route of administration Animal model Standard Inference
1 AlangiumsalviifoliumWang Alangiaceae Stem barks - 100 mg/kg petroleum ether, ethyl acetate, chloroform, methanol and aq. extract. Fruendsadjuant arthritis model Indomethacin (100 mg/kg), Extracts showed potent anti-arthritic activity.
2 AnethumgraveolensL.[24] Apiaceae Aerial parts d-carvone, d-limonene, and α-phellandrene, Dillanoside, Kaempferol- 3-glucuronide, Vicenin, Myristicin Aq. extract in sesame oil. (topical) Formalin-induced inflammation in rats Diclofenac-gel Reducing the paw inflammation significantly
(p < 0.001)
3 CaesalpiniasappanL. Leguminosae Heartwood - (1.2, 2.4 and 3.6 g/kg) p.o in olive oil-vehicle. Ethanolic extract Collagen-induced arthritis (CIA) in rats - Significantly attenuates CIA by decreasing the IL-1β, IL-6, TNF-α and PGE2 levels in serum and COX-2 transcription factor NF-κB in paw cartilage.
4 Carthamustinctorius Linn. Compositae Roots saponin 3beta-O-[beta-D-xylopyranosyl(1 --> 3)-O-beta-D-galactopyranosyl]-lup-12-ene-28 oic acid-28-O-alpha-L-rhamnopyranosyl ester Isolated from the methanolic fraction - - Showed anti-inflammatory activity in various color reactions, chemical degradations and spectral analysis.
5 Commiphora myrrh [25]. - - sesquiterpenes, diterpenes, and diterpenic acids (100, 200 mg/kg)85% ethanol extract.Fractions partitioned with petroleum ether, ethyl acetate, n-butanol, and water. Formalin-induced inflammation in mice, acetic acid induced writhing test and hot-plate test methods. dolantin and indomethacin Ethanol and pet. Ether fractions  possess analgesic and anti-inflammatory activities
6 Delonixelata(L.) Gamble Leguminosae Bark - 250 mg/kg (p.o) 40% hydro-alcoholic extract Complete freund’s adjuvant induced arthritis in rats. Diclofenac(10 mg/kg) Significant reduction in paw edema after 12 and 21 days.
7 Dichrostachyscinerea[25] Mimosoideae Leaves saponin 250 mg/kg, Carrageenan induced paw edema in rats ketoprofen (10 mg/kg) The leaves of D. cinerea possess potential anti-inflammatory
Property
8 InularacemosaHook.f[26]. Compositae Roots   Alcoholic extract. i.p&p.o Egg albumin induced passive cutaneous anaphylaxis (PCA) and mast cell degranulation in albino rats. Disodium cromoglycate(i.p) Extract possesses potent anti-allergic activity in rats.
9 JatrophacurcasL[27] Euphorbiaceae Leaves   10, 20, 40  80mg/kg  (i.p) Methanolic extract Egg albumin-induced
Rat paw oedema
Piroxicam
(0.5mg/kg i.p)
Jatrophacurcas
Extract caused statistically significant
(P < 0.001) inhibition of inflammation
Induced by egg albumin in the rats.
10 Juglansregia L [28] Juglandaceae Leaves   0.41 g/kg,  1.64 g/kg  (aq. extract), 0.292 g/kg,  1.17g/kg (eth. Extract) Cotton pellet granuloma
Method in mice.
Diclofenac (15 mg/kg) The Aqueous and ethanolic extracts indicated anti-inflammatory effects.
11 Madhucalongifolia L[29]. Sapotaceae Seed   10 and 15 mg/kg. ethanol extract. 1.5 and 3 mg/kgsaponin mixture. Acute (carrageenan-induced inflammation), sub-acute (formaldehyde-induced inflammation), and chronic (cotton pellet granuloma) models of inflammation in rats. Diclofenac sodium. Results indicated a significant anti-inflammatory activity.
12 MomordicacharantiaLinn [30]. Cucurbitaceae. Fruits Alkaloids, tannins, glycosides, steroids, proteins, and carbohydrates. 250 and 500 mg/kg, po. ethanolic extracts. Acetic acid-induced writhing and tail-immersion tests in mice, yeast-induced pyrexia in rats Aspirin (150 mg/kg, p.o.) Paracetamol (20 mg/kg, ip.) Extract shows significant analgesic and anti-pyretic activity.
13 Nyctanthes arbor-tristisLinn [31] Oleaceae Stem bark   methanolic extracts (250 and 500mg/kg, p.o.), Carrageenan-Induced pawedema Diclofenac (100 mg/kg, The
Extract reduced the rate of edema in carrageenan-induced rat paw edema model.
14 Paederiafoetida[32].   Leaves   butanol fraction of a methanol extract Cotton pellet granuloma model of inflammation in rat.   Significant inhibition of granulation tissue formation in cotton-pellet implanted rats
15 Rubiacordifolia[33]. Rubiaceae Roots   300 and 600 mg/kg.hydro-alcoholic extract Indomethacin-induced enterocolitis in rats   Pre-treatment with extract significantly prevented elevated serum LDH levels and restored it to near-normal value.
16 SemecarpusanacardiumLinn [9]. Anacardiaceae Nut   150 mg/kg Adjuvant Arthritis in Rats Indomethacin The paw swelling was completely suppressed
17 Vitex
Negundo L [34].
Lamiaceae Leaves   500 and 1000 mg/kg.(p.o) Carrageenin-induced rat paw oedema Phenylbutazone (100 mg/kg,
p.o.)
Extract significantly decreased the rat paw oedema
18 AlangiumlamarckiiThwaites[35]. Cornaceae Root   Ethanolic extract Carrageenan induced paw oedema Diclofenac sodium. Significant per cent inhibition of the maximal paw Oedema in 6h
19 AzimatetracanthaLam [10]. Salvadoraceae Leaves Friedelin hexane extract Adjuvant-induced arthritis   Friedelin inhibited 54.5% of paw thickness
20 Chaenomelesspeciosa(Sweet) [36]. Rosaceae Root   30, 60,
120 mg/kg. intragastrically
Collagen-induced arthritis in rats   Inflammatory responses were inhibited, body weight restored and immune organs weight of rats.
21 CitrulluscolocynthisSchrad Cucurbitaceae Immature fruit and seed   petroleum ether, chloroform, ethyl acetate, acetone and methanol extract Carrageenan-induced paw edema assay in rats, the acetic acid writhing test in mice   Study has demonstrated the analgesic and anti-inflammatory activities of C. colocynthis immature fruit and seed extracts.
22 Drynariaquercifolia[38]. Polypodiaceae Rhizome Catechin, coumarins, flavonoids, phenolics, saponin, steroids, tannins, and triterpenes. Oral administration, ethanolic extract Carrageenan-induced paw oedema, cotton pellet-induced granuloma in rats and acetic acid-induced writhing, formalin-induced paw licking test in mice Indomethacin,sodium salicylate and aspirin Extract significantly inhibited paw oedema and granuloma formation in rats, acute and delayed phases of formalin-induced pain and acetic acid-induced writhing  were significantly reduced in mice.
23 Ferula narthex Boiss[39]. Apiaceae     50, 100 and 200 mg/kg. (i.p.) methanolic extract Acetic acid-induced writhing model in mice Diclofenac sodium (10 mg) Effects of extract justify its
Use in folkloric medicines for the management of pain.
24 FicusbengalensisLinn [11]. Moraceae Bark   100, 200 and 300 mg/kg (i.p). methanolic extract Complete Freund’s Adjuvant induced arthritis, Formalin induced arthritis model and the Agar induced arthritis model Acetyl salicylic acid (ASA ) at 10mg/Kg Dose -dependent anti-rheumatic activity in all the models and possible action was through the central and peripherally mediated.
25 Grangeamaderaspatana(L.) Poir[29]. Compositae Whole plant   1 and 3 g/kg methanol extract Acetic acid-induced writhing in mice   Extract significantly attenuated acetic acid-induced writhing in mice by 50 and 80%, respectively. (P<0.001)
26 Hemidesmusindicus(L.) R. Br. ex Schult[12]. Apocynaceae Roots   Hydroalcoholic extract (450 mg/kg, p.o.), ethyl acetate (75 mg/kg, p.o.), Complete Freund's Adjuvant induced arthritis in rats Methotrexate Extract showed anti-arthritic activity.
27 Holarrhenapubescens(Buch.- Ham.) Wall [13. Apocynaceae Seeds Alkaloids, carbohydrate, glycosides, triterpenoids and steroids Ethanolic extract.,100, 200 and 400 mg/kg (p.o) Carrageenan-induced rat paw edema, Cotton pellet induced granuloma, Freund’s Complete adjuvant induced arthritis Indomethacin (10 mg/kg) Maximum dose 400 mg/kg of extract  inhibited the paw edema 74.07% (p<0.01). Inhibited the granuloma formation 62.63% and inhibited adjuvant induced arthritis 77.95% in rats.
28 Holopteleaintegrifolia, Planch [40]. Urticaceae Leaves   250 and 500 mg/kg.(p.o)aqueous extract Carrageenan-induced paw edema test in the male Wistar rats Indomethacin. (10 mg/kg) Extract inhibited paw swelling dose-dependently.
29 Hyoscyamusniger L. Solanaceae Seeds Coumarinolignans, cleomiscosin A Methanolic extract Carrageenin-induced paw oedema and cotton pellet granuloma methods   Significant inhibition of inflammatory responses. CleomiscosinA  significantly reduced dry and wet weight of cotton pellet granuloma in mice.
30 IlliciumverumHook.f[41]. Schisandraceae Essential oil Anethole [1-methoxy-4-(1-propenyl)benzene] 250 and 500 mg/kg. (p.o) Croton oil-induced ear edema and carrageenan-induced pleurisy   In the inflammatory exudate there significant reduction in the volume of pleural exudates, no. of migrated leukocytes, levels of nitric oxide (NO) and prostaglandins (PGE2).
31 Jasminumsambac(L.) [30]. Oleaceae Leaves   Petroleum ether extract.200 and 400 mg/kg.(p.o) Carrageenan induced paw edema. Acetic acid induced writhing in mice,tail immersion and hot plate method Diclofenac sodium (10 mg/kg, i.p.),Indomethacin (10 mg/kg, p.o), Study indicates that the extract exhibit significant Anti-nociceptive and anti-inflammatory activities
32 JusticiagendarussaBurm F [14]. Acanthaceae Leaves   100 mg/kg Freund’s adjuvant-induced and collagen-induced arthritic rat models Aspirin(360 mg/kg) Significant anti-arthritic activity that was statistically similar to that of aspirin.
33 LawsoniainermisL [42]. Lythraceae Leaves Carbohydrates, glycosides, flavonoids, saponins and tannins Methanolic extract. Acetic acid induced writhing test in mice Diclofenac sodium (20 mg/ kg) Results suggest that extract can reduce neurogenic pain stimulus.
34 Leucasaspera. (Willd.) Link[15]. Lamiaceae     Ethanolic extract. 100 and 200 mg/kg. Complete Freund's adjuvant induced arthritis Diclofenac Extract exhibited significant anti-inflammatory activity (p<0.001). In extract treated arthritic rats histopathological studies showed the complete cartilage regeneration to near normal joint.
35 Mangiferaindica L [43]. Anacardiaceae Leaves   50, 100, and 200 mg/kg ethanolic extract Monosodium
Urate Crystal-Induced Gouty Arthritis in Rats
Indomethacin (5mg/kg) Extract
Significantly decrease ankle swelling in
arthritic rats
36 PavettaindicaLinn [44]. Rubiaceae Leaves   Methanol extract Carrageenan, histamine and dextran induced paw inflammation in rats. Cotton  pellet induced granuloma in mice Indomethacin Extract significantly inhibited the inflammatory responses.
37 Piper cubeba [45].   Fruit   Oral administration (200 mg/kg) Carrageenan-induced paw edema, arachidonic acid-induced ear edema and formaldehyde-induced arthritis   Acute and sub-acute inflammations were reduced by plant extract.
38 Piper nigrumLinn [46]. Piperaceae   Piperine 10, 50 or 100μg/ml IL-β induced expression of inflammatory mediators in human osteoarthritis chondrocyte.   inhibited the production of  PGE2, NO, MMP-3, MMP-13, inos and COX-2  induced by IL-1β in human OA chondrocytes.
39 Plumbagozeylanica[47]. Plumbaginaceae Leaves Plumbagin 200 and 400 mg/kg, (p.o.)acetone extract The carrageenan induced paw oedema,the hot plate and formalin induced model Diclofenac (100 mg/kg), Morphine (10 mg/kg, i.p.) Extract significantly reduced inflammation in the rats. (p < 0.01)
40 PlumeriaacutifoliaPoir[48]. Apocynaceae Root bark Plumerianine 10, 25 50 mg/kg Cotton pellet granuloma method, carrageenan induced paw edema model. Indomethacin Significant inhibition of granuloma andpaw edema.
41 PsidiumguajavaLinn Myrtaceae Leaves   250 ,500 mg/kg p.o., ethanolic extract Adjuvant-induced arthritis method in rats Aspirin (100 mg/kg, p.o.) Shows significant dose-dependent effect.
42 Randiadumetorum
(Retz.)lamk[49].
Rubiaceae Fruit   100, 200 mg/kg Carrageenan induced
oedema model in rats.
Indomethacin Significant inhibition from edema.
43 Ricinuscommunis L Euphorbiaceae Root Lupeol, erandone 100 mg/kg p.omethanolicfraction Carrageenan-induced hind paw oedema model.   produces significant anti-inflammatory activity. (P<0.001)
44 Sidarhombifolia L.(Narendhirakannan[26]. Malvaceae Stems and roots     Adjuvant induced arthritic rats.   Arthritic symptoms were significantly reduce, especially elevated rate of erythrocyte sedimentation.

Table 2. Description of plants containing various active constituents and their action in anti-arthritic activity

A total of 14 plants with potential anti-arthritic activity have been discussed below.

Alangium salviifolium wang. (Family: Alangiaceae)

Alangium salviifolium (AS) is a small deciduous tree or shrub, grows in the wild throughout the hotter parts of India (The wealth of India, 1952). The major chemical constituents of the plant are alangine A and B, alangicine, markindine, lamarckinine and emetine. The root of AS has been used in the Indian system of medicine as an acrid, diuretic, astringent and also as a antidote for several poisons. The fruit of the plant are useful in burning sensation and haemorrhages [8]. Different extracts of stem bark of AS were found to possess anti-arthritic activity using Freunds adjuant model in rats.

Caesalpinia sappan L. (Family: Leguminosae)

Caesalpinia sappan (CS) is a traditional medicinal plant grown in Asian countries and it is mainly used for anti-inflammatory activity and it also promotes blood flow. The plant was found to possess anti-arthritic activity in collagen-induced arthritis model in rats. Different doses of ethanolic extract produced significant attenuation in paw swelling, arthritis index, radiographic and histopathological changes were evaluated.

Delonix Elata (Family: Leguminosae)

Delonix elata (DE) (white gold mohur) is used traditionally for joint pains and in flatulence. The paste of leaves and bark is used by local people to reduce inflammation and pain [9]. Bark of DE was evaluated for the anti-arthritic activity using incomplete Freund’s adjuvant induced arthritis model in rats. Hydro-alcoholic (40%) extract (250 mg/kg p.o.) was found have significant inhibiting anti-arthritic activity rat paw edema after 14 and 21 days. The results were also significant when compared with Diclofenac.

Semecarpus anacardium Linn. (Family: Anacardiaceae)

Semecarpus anacardium (SA) commonly called “marking nut” has been used in Indian medicine in the treatment of gout, rheumatic pain and cancer. SA nut extract was evaluated using adjuvant arthritis model. Treatment with SA extract (150 mg/ kg) decreased the paw edema in both developing and developed adjuvant arthritis. Results indicated that the SA nut extract is a potential anti- arthritic agent [9].

Azima tetracantha Lam (Family: Salvodoraceae)

Azima tetracantha (AT) is known as Kundali in Ayurvedic medicine and also called uppimullu in kannada [8]. There are reports that the leaves juice is efficient against toothache and earache. In Indian tribes, leaves paste of AT is used to treat snakebites. Friedelin, a compound isolated from AT. Leaves were investigated for adjuvant-induced arthritis activity in Wistar rats and 54.5% of paw thickness in rats [10].

Chaenomeles speciosa(Sweet) Nakai (Family: Rosaceae)

Chaenomeles speciosa (CS) also known as mugua, tiegenghaitang, tiejiaoli or zhoupimugua and is distributed in Central, East and Southwest China and is now cultivated worldwide. According to traditional Chinese medicine, the fruit of CS, which is warm in nature and sour in flavor, has the ability to calm the liver, relax the muscles and tendons, harmonize the stomach and eliminate dampness. Roots of CS were investigated for anti-arthritic activity using collagen-induced arthritis model in rats. Doses of 30, 60, 120 mg/kg of extract inhibited the inflammatory response and restored body weight in arthritic rats.

Ficus bengalensis Linn (Family: Moraceae)

Ficus bengalensis (FB) is commonly known as Banyan tree [8] and is used in Ayurveda for diarrhea, dysentery, hypoglycemic, astringent, rheumatism as well as it was applied to gums to lessen inflammation. The bark of FB was investigated for its antirheumatic activity using the Complete Freund’s Adjuvant induced, formalin induced and Agar induced arthritis models. The extract (100, 200 and 300 mg/kg, i.p.) showed significant inhibitory effect on edema especially on secondary immunological arthritis and inhibited Formalin- induced pain [11].

Hemidesmus indicus R.Br (Family: Asclepiadaceae)

Hemidesmus indicus (HI) has been used in Ayurvedic and Unani medicine against blood disorders of blood and inflammation. Hydro-alcoholic extract (450 mg/kg, p.o.), ethyl acetate (75 mg/kg, p.o.), chloroform (60 mg/kg, p.o) and residual fractions (270 mg/kg, p.o.), was evaluated by using Complete Freund's adjuvant arthritis rat models. The study showed significant decrease in paw edema, body weight, arthritic index, erythrocyte sedimentation rate, serum rheumatoid factor, serum C-reactive protein, and serum nitrite level [12].

Holarrhena pubescens (Buch.- Ham.) Wall. (Family: Apocynaceae)

Holarrhena pubescens (HP) is an Indian traditional medicinal plant, is commonly known as ‘kurchi’ in India (Kirtikar Basu and Nadkarni). Ethanolic extract of dried seeds of HP were investigated for their anti-inflammatory and anti-arthritic activity. HP (400 mg/kg p.o.) extract showed maximum (74.07%) inhibition of carrageenan-induced rat paw edema, 62.63% inhibition of granuloma formation and 77.95% inhibition of adjuvant induced arthritic edema in rats when compared with Indomethacin [13].

Justicia gendarussa Burm F. (Family: Acanthaceae)

Justicia gendarussa (JG) is used in Indian and Chinese traditional medicine, the leaves of the plant is recommended to treat ailments such as rheumatism, arthritis, headache, earache, respiratory disorders, and digestive trouble. The anti-arthritic potential JG was evaluated using freund’s adjuvant-induced and collagen-induced arthritic rat models. The animals were treated with dose of 100 mg/kg of ethanolic extract of JG and with standard drug aspirin (360 mg/kg) showed significant anti-arthritic activity [14].

Leucas aspera (Family: Labiatae)

Leucas aspera (LA) is traditionally used for analgesic, antipyretic, antirheumatic, anti-inflammatory and antibacterial treatment and its paste is applied topically to inflamed areas.The chronic anti-inflammatory activity of ethanolic extract of LA was investigated using complete Freund’s adjuvant arthritis model. A dose of 100 and 200 mg/kg exhibited significant antiinflammatory activity (p<0.001). After the treatment, histopathological studies confirmed complete cartilage regeneration and near normal joint [15].

Mangifera indica L. (Family: Anacardiaceae)

Mangifera indica (MI) is the largest fruit-tree, has been recently reported for inhibiting lipid peroxidation, antifungal activity and anti-ulcerogenic action.Therapeutic effects of the ethanol extract from MI were investigated using monosodium urate crystalsinduced gouty arthritis model in rats. Oral administration of ethanolic extract (100 and 200 mg/kg, p.o for 9 days) significantly ameliorated the abnormalities in ankle swelling, synovial TNF-α, IL-1β mRNA and protein levels indicating the beneficial effect of MI in gouty arthritis .

Psidium guajava Linn. (Family: Myrtaceae)

Psidium guajava (PG), commonly known as Guava, is used in the traditional medicine for the treatment of wounds, ulcers, bowels, and cholera (Begum et al.). Leaves of PG were evaluated for adjuvant-induced arthritis in rats. Dose of 250 and 500 mg/ kg p.o. of ethanolic extract of PG produced significant dose-dependent anti-arthritic activity in complete freund’s adjuvant-induced arthritis model.

Sida rhombifolia (Family: Malvaceae)

Sida rhombifolia (SR) has been used from prehistoric times for the treatment of gout in Indonesia. Effect of SR stem and root extracts using adjuvant induced arthritis model in experimental rats were evaluated. Extract was found to normalize the altered levels of hematological parameters. The elevated rate of erythrocyte sedimentation was also significantly reduced [16].

Discussion and Conclusion

Appropriate management of arthritis can reduce pain and help to overcome functional limitations to a greater extent. Medication, physical or occupational therapy, patient education, weight loss, and surgery may be included in treatment and management of arthritis [17]. Though conventional treatment of rheumatoid arthritis is improving, treatment still remains unsatisfactory as remission is rare. Therefore, search remains on going for effective alternative and additional therapies for this disease. A number of inexpensive herbal medicines have been reported in literature to be useful in rheumatoid arthritis due to their anti-inflammatory and immunosuppressive potential. The literature of Ayurveda describes various plants, to be used as whole, in part or as extracts for treating painful and inflammatory conditions like arthritis. Matricaria chamomilla Linn., Cichorium intybus Linn., Rhododendron campanulatum, Plumbago rosea Linn., Salvadora oleoides, Acacia polyantha is being used traditionally to ameliorate painful inflammatory conditions but have not been yet explored experimentally in the treatment of arthritis. Although plant extracts or individual compounds derived from plants exhibit high potential but the underlying molecular mechanism has not been sufficiently elucidated. There is a need to identify the active principals of these medicines as potential chemotherapeutic agents and monitor the safety of these active constituents [18]. Thus, we need a scientific approach towards phytotherapeutics to deliver the components in a sustained manner by formulating novel drug delivery systems so as to increase patient compliance and minimize the need for repeated administration.

References