Potential Anti-Arthritic Agents From Indian Medicinal Plants

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].

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).

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).

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

1. Silman AJ and Pearson JE. Epidemiology and genetics of rheumatoid arthritis. Arthritis Res. 2002;4:265-72.
2. Gerald Weismann. The Pathogenesis of Rheumatoid Arthritis.Bulletin of the NYU Hospital for Joint Diseases 2006;6:12-15.
3. Isler P,et al. Cell surface glycoproteins expressed on activated human T cells induce production of interleukin-1 beta by monocytic cells: a possible role of CD69. Eur Cytokine Netw. 1993;4:15-23.
4. Harris ED Jr. Mechanisms of disease: rheumatoid arthritis pathophysiology and implications for therapy. N Engl J Med.1990;322:1277-1289.
5. Paget SA and Gibofsky A. Immunopathogenesis of rheumatoid arthritis. Am J Med.1979;67:961-970.
6. Nepom GT,et al. HLA genes associated with rheumatoid arthritis: Identification of susceptibility alleles using specific oligonucleotide probes. Arthritis Rheum. 1989;32:15-21.
7. Van der LindenMP,et al.Value of anti-modified citrullinatedvimentin and third-generation anti-cyclic citrullinated peptide compared with second-generation anti-cyclic citrullinated peptide and rheumatoid factor in predicting disease outcome in undifferentiated arthritis and rheumatoid arthritis.Arthritis Rheum.2009;60:2232-2241.
8. Kritikar KR and Basu BD. In:Indian medicinal plants. Vol 2. 2ndedn. Allahabad: Publ. Lalit Mohan Basu; 1991.
9. VanuRamkumarRamprasath,et al. Anti-inflammatory effect of semecarpusanacardiumlinn. Nut extract in Acute and chronic inflammatory conditions. Biol. Pharm. Bull. 2004;27:2028-2031
10. Antonisamy P,et al. Anti-inflammatory, analgesic and antipyretic effects of friedelin isolated fromazimatetracanthalam. In mouse and rat models. J Pharm Pharmacol.2011;63:1070-1077.
11. Manocha N, et al.Evaluation of anti-rheumatic activity of extract of stem bark of ficusbengalensisJournal of Global Pharma Technology. 2011;3:31-37.
12. Mehta A,et al. Anti-arthritis activity of roots ofhemidesmusindicusr.br. (anantmul) in rats. Asian Pac J Trop Med.2012;5:130-5.
13. Saha S and Subrahmanyam EVS.Evaluation of anti-inflammatory activity of ethanolic extract of seeds of holarrhenapubescens(buch.- ham.) Wall Int J Pharm Pharm Sci. 5:915-919
14. JaijeshPaval, et al. Anti-arthritic potential of the plant justiciagendarussaburm f. Clinics 2009;64:357-60
15. Kripa KG,et al. Modulation ofinflammatorymarkers by the ethanolic extract ofleucasasperain adjuvant arthritis. J Ethnopharmacol.2011;134:1024-7.
16. Narendhirakannan andLimmy TP. Anti-inflammatory and anti-oxidant properties ofsidarhombifoliastems and roots in adjuvant induced arthritic rats. Immunopharmacol immunotoxicol.2012;34:326-36
17. Fantini F. New drugs and treatment strategies for rheumatoid arthritis. Recenti Prog Med. 2003;94:361-79.
18. Gogtay NJ, et al. The use and safety of non-allopathic Indian medicines. Drug Saf. 2002;25:1005-19.
19. AryaVaidyaSala. Indian medicinal plants, A compendium of 500 species. Vol-1. Universities press (India) private limited. 2010;30-101.
20. AryaVaidyaSala. Indian medicinal plants, A compendium of 500 species. Vol-2. Universities press (India) private limited. 2010;11-389.
21. AryaVaidyaSala. Indian medicinal plants, A compendium of 500 species. Vol-3. Universities press (India) private limited. 2010;1-390.
22. AryaVaidyaSala. Indian medicinal plants, A compendium of 500 species. Vol-4. Universities press (India) private limited. 2010;6-395.
23. AryaVaidyaSala. Indian medicinal plants, A compendium of 500 species. Vol-5. Universities press (India) private limited. 2010;1-403.
24. Mohsen Naseri, et al. The study of anti-inflammatory activity of oil-based dill (anethumgraveolensl.) Extract used topically in formalin-induced inflammation male rat paw. Iranian Journal of Pharmaceutical Research. 2012;11:1169-1174.
25. Hassan H, et al. Anti-inflammatory activity of crude saponin extracts from five nigerian medicinal plants.Afr J TraditComplement Altern Med. 2012;9:250-255.
26. Srivastava P,et al. New anti-inflammatorytriterpene from the root ofricinuscommunis. Nat Prod Res.2014;28:306-11.
27. Uche FI and Aprioku JS. The phytochemical constituents, analgesic and anti-inflammatory effects of methanol extract of jatrophacurcasleaves in mice and wister albino rats. J. Appl. Sci. Environ. Manage. 2008;12:99-102.
28. H Hosseinzadeh, et al. Antinociceptive, anti-inflammatory and acute toxicity effects of juglansregia. Leaves in mice. Iran Red Crescent Med J. 2011;13:27-33
29. Ramchandra D, et al. Anti-inflammatory activity ofMadhucalongifoliaseed saponin mixture. 2009; 47: 592-597
30. JitendraBhangale, et al. Preliminary studies on anti-inflammatory and analgesic activities of jasminumsambac(l.) Aiton in experimental animal models. Am. J. Pharmtech res. 2012;2:1.
31. BibhutiBhusan, et al. Analgesic and anti-inflammatory activities of the methanolic stem bark extract of nyctanthes arbor-tristislinn. Biomed Research International 2013;8:262-295.
32. De B, et al. Investigation of the anti-inflammatory effects ofpaederiafoetidasubrata. Journal of Ethnopharmacology. 1994;43:31–38
33. Kritikar Pawar AT, et al. Protective effect of hydroalcoholic root extract of rubiacordifolia in indomethacin-induced enterocolitis in rats. Indian J Pharm Sci. 2011;73:250-3.
34. Telang RS. Studies on analgesic and anti-inflammatory activities of Cedrusdeodara (Roxb.) Loud. wood oil.1999;65:21-7.
35. Ahad, et al. Phytochemical and anti-inflammatory evaluation of alangiumlamarckiiroot extract. derpharmaciasinica. 2011;2:119-129.
36. Qun Chen and Wei Wei. Effects and mechanisms of glucosides of chaenomelesspeciosa on collagen-induced arthritis in rats. International Immunopharmacology 2003;3:593-608
37. Marzouk B,et al. Anti-inflammatory and analgesic activities tunisiancitrulluscolocynthisschrad.immature fruit and seed organic extracts. Eur Rev Med Pharmacol Sci.2011;15:665-72.
38. Anuja GI,  et al. Anti-inflammatory and analgesic properties of drynariaquercifolia (l.) J Ethnopharmacol. 2010;132:456-60.
39. Shumaila Bashir, et al. Screening of ferula narthex boiss crude methanolic extract for analgesic, gastrointestinal motility and insecticidal activity. Middle-East Journal of Scientific Research 2013;14:471-475.
40. Shrinivas Sharma, et al. Studies on anti-inflammatory effect of aqueous extract of leaves of holopteleaintegrifolia, planch in rats. Indian J Pharmacol.2009;41:87-88.
41. Domiciano TP,et al.Inhibitory effect of anethole in nonimmune acute inflammation. Naunynschmiedebergs Arch Pharmacol.2013;386:331-8.
42. Imam H,et al. Alpha amylase enzyme inhibitory and anti-inflammatoryeffect oflawsoniainermis. Pak J Biol Sci.2013;16:1796-800.
43. Yan Jiang, et al. Effects of extract frommangiferaindica leaf onmonosodiumurate crystal-induced gouty arthritis in rats. Evidence-based complementary and alternative medicine. 2012;967573: 6 pages.
44. Mandal SC,et al. Evaluation of anti-inflammatory potential ofpavettaindicalinn.leaf extract (family: rubiaceae) in rats. Phytother res.2003;17:817-20.
45. Choi EM and Hwang JK. Investigations of anti-inflammatory and antinociceptive activities ofpiper cubeba, physalisangulata and rosahybrida. J ethnopharmacol.2003;89:171-5.
46. Ying X,et al.Piperine inhibits il-β induced expression ofinflammatorymediators in human osteoarthritis chondrocyte. Int Immunopharmacol.2013;17:293-9.
47. Sheeja E,et al.Bioassay-guided isolation of anti-inflammatory and antinociceptive compound fromplumbagozeylanicaleaf. Pharm biol.2010;48:381-387.
48. A Vijayalakshmi, et al. Anti-anaphylactic and anti-inflammatory activities of a bioactive alkaloid from the root bark of plumeriaacutifoliapoir. Asian Pac J Trop Biomed 2011;1:401-405.
49. Mahavir H, et al. Bronchorelaxant, mast cell stabilizing, anti-inflammatory and antioxidant activity of randiadumetorum (retz.) Lamk. Extracts. ActaPoloniaePharmaceutica Drug Research. 2012;69:465-474.