RHEUMATOID ARTHRITIS: MOLECULAR BASIS AND CURES FROM NATURE
Keywords:
Rheumatoid arthritis, Medicinal plantAbstract
Incidences of arthritic diseases in human have seen recent increases which are thought to have resulted from a complex interplay of several factors, such as changes in lifestyle, nutritional insufficiencies, aging and genetic factors. These putative factors possibly lead to different arthritic diseases in humans affecting 2-5% of the total population in India. This group of diseases results in serious malfunction and structural abnormalities in the patient body leading to permanent and substantial immovability of joints. Conventional medicinal systems usually elicit various side effects in which the defence mechanism of the body i.e. the immune system is compromised. In the last few decades many alternative medicinal systems have been developed that show promising effects on treating such diseases. Many purified compounds from natural origin, both from plants and animal sources have shown promise and many new compounds are continuingly being identified which have no marked side effects. In the light of modern science and technology, different natural products and ethnic practices that ensure health, seem to be the best weapon to combat these diseases. Endemic as well as naturalized plants from India have been screened by several groups for their anti-arthritic activities. The review summarizes our current knowledge on the molecular basis of Rheumatoid Arthritis and discusses the efficacious roles of those natural products, especially of plant origin, in arthritic conditions.
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References
Firestein GS. Evolving concepts of rheumatoid arthritis. Nature 2003;423:356-61.
Williams RO, Mason LJ, Feldmann M, Maini RN. Synergy between anti-CD4 and antitumor necrosis factor in the amelioration of established collagen-induced arthritis. Proc Natl Acad Sci USA 1994;91:2762–6.
Lubberts E, Van Der Bersselaar L, Oppers-Walgreen B, Schwarzenberger P, Conen-de Roo CJJ, Kolls JK, et al. IL-17 promotes bone erosion in murine collagen-induced arthritis through loss of the receptor activator of NF-kB ligand/osteoprotegerin balance. J Immunol 2003;170:2655–62.
Smolen JS, Steiner G. Rheumatoid arthritis is more than cytokines: autoimmunity and rheumatoid arthritis. Arthritis Rheum 2001;44:2218–20.
Arnett FC, Edworthy SM, Bloch DA. The american rheumatism association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988;31:315–24.
Gabriel SE. The epidemiology of rheumatoid arthritis. Rheum Dis Clin North Am 2001;27:269–82.
Chopra A, Ahmed AN. Epidemiology of rheumatic musculoskeletal disorders in the developing world. Best Pract Res Clin Rheumatol 2008;22(4):583–604.
Schellekens GA, DeJong W, Van den Hoogen FHJ, Van de Putte LBA, Van Venrooj W. Citrulline is anessential constituent of antigenic determinants recognized by rheumatoid arthritis-specific autoantibodies. J Clin Invest 1998;10:273–81.
Stahl EA, Raychaudhuri S, Remmers EF, Xie G, Eyre S, Thomson BP, et al. Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci. Nat Gen 2010;42(6):508-14.
Thomas R, MacDonald KPA, Pettit AR, Cavanagh LL, Padmanabha J, Zehntner S. Dendritic cells and the pathogenesis of rheumatoid arthritis. J Leukocyte Biol 1999;66:286-92.
Cavanagh LL, Boyce A, Smith L, Padmanabha J, Filgueira L, Pietschmann P, et al. Rheumatoid arthritis synovium contains plasmacytoid dendritic cells. Arthritis Res Ther 2005;7:R230-R40.
Cope AP. T-cells in rheumatoid arthritis. Arthritis Res Ther 2008;10(Suppl 1):S1.
Kinne RW, Bräuer R, Stuhlmüller B, Palombo-Kinne E, Burmester GR. Macrophages in rheumatoid arthritis. Arthritis Res 2000;2:189–202.
Kinne RW, Stuhlmüller B, Burmester GR. Cells of the synovium in rheumatoid arthritis Macrophages. Arthritis Res Ther 2007;9:224.
Redlich K, Hayer S, Ricci R, David JP, Tohidast-Akrad M, Kollias J, et al. Osteoclasts are essential for TNF-a-mediated joint destruction. J Clin Invest 2002;110:1419–27.
Goldring R. Pathogenesis of bone and cartilage destruction in rheumatoid arthritis. Rheum 2003;42(Suppl 2):11–6.
Silverman GJ, Carson DA. Roles of B-cells in rheumatoid arthritis. Arthritis Res Ther 2003;5(4):S1-6.
Rathore B, Mahdi AA, Paul BN, Saxena PN, Das SK. Indian herbal medicines: possible potent therapeutic agents for rheumatoid arthritis. J Clin Biochem 2007;41(1):17-9.
Begovich AB, Carlton VEH, Honigberg LA, Schrodi SJ, Chokkalingam AP, Alexander HC, et al. A missense single-nucleotide polymorphism in a gene encoding a protein tyrosine phosphatase (PTPN22) is associated with rheumatoid arthritis. Am J Hum Genet 2004;75:330-7.
Kallberg H, Padyukov L, Plenge RM, Ronnelid J, Gregersen PK, van der Helm-van Mil AHM, et al. Gene-gene and gene-environment interactions involving HLA-DRB1, PTPN22, and smoking in two subsets of rheumatoid arthritis. Am J Hum Genet 2007;80:867-75.
Weyand CM, Hicock KC, Conn DL, Goronzy JJ. The influence of HLA-DRB1 gene on disease severity in rheumatoid arthritis. Ann Inter Med 1992;117(10):801-6.
Yang H, Rittner H, Weyand CM, Goronzy JJ. Aberrations in the primary T-cell receptor repertoire as a predisposition for synovial inflammation in rheumatoid arthritis. J Invest Med 1999;47:236–5.
Nabil M, Yanni G, Poston R, Panayi GS. Cytokine expression in synovial membranes of patients with rheumatoid arthritis. Ann Rheum Dis 1994;52:870-5.
Ulfgren AK, Lindblad S, Klareskog L, Anderson J, Anderson U. Detection of cytokine producing cells in the synovial membrane from patients with rheumatoid arthritis. Ann Rheum Dis 1995;54:654-61.
Buchan G, Barret K, Turner M, Chantry D, Maini RN, Feldmann M. Interleukin-1 and tumor necrosis factor-α mRNA expression in rheumatoid arthritis, prolonged production of IL-1 α. Clin Exp Immunol 1988;3:449-55.
Firestein GS, Alvaro-Gracia JM, Maki R. Quantitative analysis of cytokine gene expression in rheumatoid arthritis. J Immunol 1990a;144:3347–53.
Klimiuk PA, Goronzy JJ, Bjornsson J, Beckenbaugh RD, Weyand CM. Tissue cytokine patterns distinguish variants of rheumatoid synovitis. Am J Pathol 1997;151:1311–9.
Reveille JD. The genetic contribution to the pathogenesis of rheumatoid arthritis. Curr Opin Rheumatol 1998;10:187–200.
Auger I, Roudier J. HLA-DR and the development of rheumatoid arthritis. Autoimmunity 1997;26:123–8.
Lipsky PE, Van Der Heijde DM, St Clair EW, Furst DE, Breedveld FC, Kalden JR, et al. Infliximab and methotrexate in the treatment of rheumatoid arthritis. Anti-Tumor necrosis factor trial in rheumatoid arthritis with concomitant therapy study group. N Engl J Med 2000;343:1594–602.
Ziolkowska M, Kurowska M, Radzikowska A. High levels of osteoprotegerin and soluble receptor activator of nuclear factor kB ligand in serum of rheumatoid arthritis patients and their normalization after anti-tumor necrosis factor a treatment. Arthritis Rheum 2002;46:1744–53.
Kong YY, Feiqe U, Bolon B, Tafuri A, Morony S, Capparelli C, et al. Activated T-cells regulate bone loss and joint destruction in adjuvant arthritis through osteoprotegerin ligand. Nature 1999;402(6759):304-9.
Pettit AR, Ji H, Stechow DV, Muller R, Goldring SR, Choi Y, et al. Trance/Rankl knockout mice are protected from bone erosion in a serum transfer model of arthritis. Am J Pathol 2001;159:1689–99.
Han Z, Boyle DL, Manning AM, Firestein GS. AP-1 and NF-kB regulation in rheumatoid arthritis and murine collagen-induced arthritis. Autoimm 1998;28:197–208.
Aupperle K. NF-kB regulation by IkB kinase-2 in rheumatoid arthritis synoviocytes. J Immunol 2001;166:2705–11.
Tak PP, Gerlag DM, Aupperle KR, van de Geest DA, Overbeek M, Bennett BL, et al. Inhibitor of nuclear factor kB kinase b is a key regulator of synovial inflammation. Arthritis Rheum 2001;44:1897–907.
Miagkov AV, Kovalenko DV, Brown CE, Didsbury JR, Cogswell JP, Stimpson SA, et al. NF-kB activation provides the potential link between inflammation and hyperplasia in the arthritic joint. Proc Natl Acad Sci USA 1998;95:13859–64.
Schett G, Tohidast-Akrad M, Smolen JS, Schmid BJ, Steiner CL, Bitzan P, et al. Activation, differential localization, and regulation of the stress-activated protein kinases, extracellular signal-regulated kinase, c-JUN N-terminal kinase, and p38 mitogen-activated protein kinase, in synovial tissue and cells in rheumatoid arthritis. Arthritis Rheum 2000;43:2501–12.
Badger AM, Bradbeer JN, Votta B, Lee JC, Adams JL, Griswold DE. Pharmacological profile of SB 203580, a selective inhibitor of cytokine suppressive binding protein/p38 kinase, in animal models of arthritis, bone resorption, endotoxin shock and immune function. J Pharmacol Exp Ther 1996;279:1453–61.
Han Z, Boyle DL, Chang L, Bennet B, Karin M, Yang L, et al. c-Jun N-terminal kinase is required for metalloproteinase expression and joint destruction in inflammatory arthritis. J Clin Invest 2001;108:73–81.
Han Z, Chang L, Yamanishi Y, Karin M, Firestein GS. Joint damage and inflammation in c-Jun N-terminal kinase 2 knockout mice with passive murine collagen-induced arthritis. Arthritis Rheum 2002;46:818–23.
Kinne RW, Boehm S, Iftner T, Aigner T, Vornehm S, Weseloh G, et al. Synovial fibroblast-like cells strongly express jun-B and C-fos proto-oncogenes in rheumatoid-and osteoarthritis. Scand J Rheumatol 1995;101:121–5.
Shiozawa S, Shimizu K, Tanaka K, Hino K. Studies on the contribution of c-fos/AP-1 to arthritic joint destruction. J Clin Invest 1997;99:1210–6.
Moreland LW, Baumqartner SW, Schiff MH, Tindall EA, Fleischmann RM, Weaver AL, et al. Treatment of rheumatoid arthritis with a recombinant human tumor necrosis factor receptor (p75)-Fc fusion protein. N Engl J Med 1997;337:141–7.
Elliott MJ, Maini RN, Feldmann M, Kalden JR, Antoni C, Smolen JS, et al. Randomised double-blind comparison of chimeric monoclonal antibody to tumour necrosis factor alpha (cA2) versus placebo in rheumatoid arthritis. Lancet 1994;344:1105–10.
Brennan FM, Chantry D, Jackson A, Maini R, Feldmann M. Inhibitory effect of TNFα antibodies on synovial cell interleukin-1 production in rheumatoid arthritis. Lancet 2001;2:244–7.
Lubberts E, Joosten LA, Van Der Bersselaar L, Oppers B, Conen-de Roo CJJ, Richards CD, et al. IL-4 gene therapy for collagen arthritis suppresses synovial IL-17 and osteoprotegerin ligand and prevents bone erosion. J Clin Invest 2000;105:1697–710.
Smeets TJ, Kraan MC, Versendaal J, Breedveld FC, Tak PP. Analysis of serial synovial biopsies in patients with rheumatoid arthritis: description of a control group without clinical improvement after treatment with interleukin 10 or placebo. J Rheumatol 1999;26:2089–93.
Efthimiou P, Kukar M, Mackenzie CR. Complementary and alternative medicine in rheumatoid arthritis: no longer the last resort! HSSJ 2010;6:108-11.
World Health Organization. General guidelines for methodologies on research and evaluation of traditional medicine. WHO/EDM/TRM 2000;1:1-74.
Ahmed S, Anuntiyo J, Malemud CJ, Haqqi TM. Biological basis for the use of botanicals in osteoarthritis and rheumatoid arthritis. eCAM 2005;2(3):301–8.
Manami M, Kaori E, Fumiko K, Mari Maeda Y. Immunostimulating activity of a crude polysaccharide derived from green tea (Camellia sinensis) Extract. J Agric Food Chem 2008;56(4):1423–7.
Hamilton-Miller JM. Antimicrobial properties of tea (Camellia sinensis L.). Antimicrob Agents Chemother 1995;39(11):2375–7.
Liacini A, Sylvester J, Li WQ, Zafarullah M. Inhibition of interleukin-1-stimulated MAP kinases, activating protein-1 (AP-1) and nuclear factor kappa β (NF-kappa β) transcription factors down-regulates matrix metalloproteinase gene expression in articular chondrocytes. Matrix Biol 2002;21(3):251–62.
Schulze-tanzilG, Mobasheri A, Sendzik J, John T, Shakibaei M. Effects of curcumin (diferuloylmethane) on nuclear factor kappaβ signaling in interleukin-1betastimulated chondrocytes. Ann N Y Acad Sci 2004;1030:578–86.
Kukar M. Complementary and alternative medicine use in rheumatoid arthritis: proposed mechanism of action and efficacy of commonly used modalities. Rheumatol Int 2010;30:571–86.
Lee TY, Lee KC, Chen SY, Chang HH. 6-Gingerol inhibits ROS and iNOS through the suppression of PKC-α and NF-κβ pathways in lipopolysaccharide-stimulated mouse macrophages. Biochem Biophys Res Commun 2009;382(1):134–9.
Srivastava KC, Mustafa T. Ginger (Zingiber officinale) and rheumatic disorders. Med Hypotheses 1989;29(1):25–28.
Srivastava KC, Mustafa T. Ginger (Zingiber officinale) in rheumatism and musculoskeletal disorders. Med Hypotheses 1992;39(4):342–8.
Ramprasath VR, Shanthi P, Sachdanandam P. Immunomodulatory and anti-inflammatory effects of Semecarpus anacardium LINN. Nut milk extract in experimental inflammatory conditions. Biol Pharm Bull 2006;29(4):693–700.
Vijayalakshmi T, Muthulakshmi V, Sachdanandam P. Effect of the milk extract of Semecarpus anacardium nut on adjuvant arthritis—a dose-dependent study in Wistar albino rat. Gen Pharmacol 1996;27(7):1223–6.
Ramprasath VR, Shanthi P, Sachdanandam P. Effect of Semecarpus anacardium Linn. nut milk extract on rat neutrophil functions in adjuvant arthritis. Cell Biochem Funct 2006;24(4):333–40.
Gupta M, Sasmal S, Mukherjee A. Therapeutic effects of acetone extract of saraca asoca seeds on rats with adjuvant-induced arthritis via attenuating inflammatory responses. Int Scho Res Notices ISRN Rheum 2014;4:1-12.
Saravanan S, Prakash B, Pandikumar P, Ignacimuthu S. Therapeutic effect of Saraca asoca (Roxb.)Wilde on lysosomal enzymes and collagen metabolism in adjuvant induced arthritis. Inflammopharmacology 2011;19:317–25.
Mondal S, Bhattacharya S, Pandey JN, Biswas M. Evaluation of acute anti-inflammatory effect of Ananus comosus leaf extracts in rats. Pharmacologyonline 2011;3:1312-5.
Walker AF, Bundy R, Hicks SM, Middleton RW. Bromelain reduces mild acute knee pain and improves well being in a dose dependent fashion in an open study of otherwise healthy adults. Phytomed 2002;9(8):681-6.
Costa B, Colleoni M, Conti S, Parolaro D, Franke C, Trovato AE, et al. Oral anti-inflammatory activity of cannabidiol, a non-psychoactive constituent of cannabis, in acute carrageenan-induced inflammation in the rat paw. Naunyn-Schmiedeberg’s Arch Pharmacol 2004;369:294-9.
Takeda S, Misawqa K, Yamamoto I, Watanabe K. Cannabidiolic acid as a selective cyclooxygenase-2 inhibitory component in cannabis. Drug Metab Dispos 2008;36(9):1917-21.
Rieder SA, Chauhan A, Singh U, Nagarkatti M, Nagarkatti P. Cannabinoid-induced apoptosis in immune cells as a pathway to immunosuppression. Immunobiol 2010;215(8):598–605.
Singh S, Majumder DK. Effect of fixed oil of ocimum sanctum against experimentally induced arthritis and joint edema in laboratory animals. Pharm Biol 1996;34(3):218-22.
Rasool M, Latha LM, Varalakshmi P. Effect of Withania somnifera on lysosomal acid hydrolases in adjuvant-induced arthritis in rats. Pharm Pharmacol Commun 2000;6:187–90.
Rasool M, Latha LM, Varalakshmi P. Immunomodulatory role of Withania somnifera root powder on experimental induced inflammation: An in vivo and in vitro study. Vascu Pharmacol 2006;44(6):406–10.
Rasool M, Varalakshmi P. Protective effect of Withania somnifera root powder in relation to lipid peroxidation, antioxidant status, glycoproteins and bone collagen on adjuvant-induced arthritis in rats. Fundam Clin Pharmacol 2007;21:157–64.
Singh D, Aggarwal A, Maurya R, Naik S. Withania somnifera inhibits NF-κB and AP-1 transcription factors in human peripheral blood and synovial fluid mononuclear cell. Phytoth Res 2007;21:905–13.
Khade CP. Indian medicinal plants-An illustrated dictionary. First Indian Reprint: Springer (India) Pvt. Ltd. New Delhi; 2007. p. 717-8.
Mahajan SG, Mehta AA. Immunosuppressive activity of ethanolic extract of seeds of Moringa oleifera Lam. in experimental immune inflammation. J Ethnopharmacol 2010;130(1):183–6.
Sashidhara KV, Rosaiah JN, Tyagi E, Shukla R, Raghubir R, Rajendran SM. Rare dipeptide and urea derivatives from roots of Moringa Oleifera as potential anti-inflammatory and antinociceptive Agents. Eur J Med Chem 2009;44(1):432-6.
Latha RM, Geetha T, Varalakshmi P. Effect of Vernonia cinerea less flower extract in adjuvant-induced arthritis general pharmacology. Vasc Syst 1998;31(4):601–6.
Kumar PP, Kuttan G. Vernonia cinerea L. scavenges free radicals and regulates nitric oxide and proinflammatory cytokines profile in carrageenan induced paw edema model. Immunopharmacol Immunotoxicol 2009;31(1):94-102.
Sikha P, Latha PG, Suja SR, Anuja GI, Shyamal S, Shine VJ, et al. Anti-inflammatory and antinociceptive activity of Justicia gendarussa Burm. F. leaves. Indian J Nat Prod Resour 2010;1(4):456-61.
Chinna M, Renuka P, Fazaludeen MF. Evaluation of anti-inflammatory activity on justicia genadarussa burm. f. Leaf extract in adjuvant induced arthritic rats. Int J Medicobiol Res 2011;1(3):163-9.
Kavitha SK, Viji V, Kripa K, Helen A. Protective effect of Justicia gendarussa Burm. f. on carrageenan-induced inflammation. J Nat Med 2011;65(3-4):471-9.
Rajendran R, Krishnakumar E. Anti-arthritic activity of premna serratifolia Linn. Wood against adjuvant induced arthritis. Avicenna J Med Biotechnol 2010;2(2):101-6.
Amaresh G, Reddy GD. Evaluation of anti inflammatory properties of Cissampelos pareira roots in rats. J Ethnopharmacol 2007;110(3):526-31.
Paul BN, Saxena AK. Depletion of TNF-α in mice by Nyctanthes arbortristis. J Ethnopharmacol 1997;56:153.
Kumar IV, Paul BN, Asthana A, Saxena A, Mehrotra S, Rajan G. Swertia chirayita mediated modulation of IL-1β, IL-6, IL-10, IFN-γ and TNF-α in arthritic mice. Immunopharmacol Immunotoxicol 2003;25:573–83.
Hossein H, Younesi H. Antinociceptive and anti-inflammatory effects of Crocus sativus L. stigma and petal extracts in mice. BMC Pharmacol 2002;2;7.
Agarwal R, Rangari V. Anti-inflammatory and anti-arthritic activities of lupeol and 19α-H lupeol isolated from Strobilanthus callosus and Strobilanthus ixiocephala roots. Indian J Pharmacol 2003;35:384–7.
Grindley D, Reynolds T. The aloe vera phenomenon: a review of the properties and modern uses of the leaf parenchymal gel. J Ethnopharmacol 1986;16:117-51.
Paul S, Dutta S, Chaudhuri TK, Bhattacharjee S. Anti-Inflammatory and Protective properties of Aloe vera leaf crude gel in carrageenan induced acute inflammatory Rat Models. Int J Pharm Pharm Sci 2014:6(9);368-71.
Guha P, Paul S, Das A, Halder B, Bhattacharjee S, Chaudhuri TK. Analyses of human and rat clinical parameters in rheumatoid arthritis raise the possibility of use of crude Aloe vera gel in disease amelioration. Immunome Res 2014;10(2). DOI: 10.4172/17457580.1000081 [Article in Press].
Hukkeri VI, Savadi RV, Tippimath CD, Karadi RV, Jaiprakash B. Anti-inflammatory activity of leaves of Acacia farnesiana Willd. Indian Drugs 2002;49(13):664-6.
Gurulingappa S, Halur MS. Anti–inflammatory assays of extracts of medicinal plants. Indian J Pharm Sci 2002;64(5):498-500.
Mota ML, Thomas RG. Anti inflammatory actions of tannins isolated from the bark of Anancardium occidentale L. J Ethnopharmacol 2002;13:289-300.
Chttpadhyay RR. Possible biochemical mode of anti-inflammatory action of Azadirachta indica A. Juss in rats. Indian J Exp Biol 1998;36(4):418-20.
Shinde UA, Phadke AM. Studies on the anti inflammatory and analgesic activity of Cedrus deodara (Roxb.) Loud wood oil. J Ethnopharmacol 1999;65(1):21-7.
Balasubramanian A, Ramalingam K. Anti-inflammatory activity of Morus indica. Linn. Iranian J Pharmacol Ther 2005;4(1):13-5.
Shylesh BS, Padikkala J. Antioxidant and anti inflammatory activity of Emilia sonchifolia. Phytother 1999;70(3):L275-8.