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Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry

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ISSN (Print): 1871-5230
ISSN (Online): 1875-614X

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Research Article

In vivo, Extract from Withania somnifera Root Ameliorates Arthritis via Regulation of Key Immune Mediators of Inflammation in Experimental Model of Arthritis

Author(s): Mahmood Ahmad Khan*, Rafat Sultana Ahmed, Nilesh Chandra, Vinod Kumar Arora and Athar Ali

Volume 18, Issue 1, 2019

Page: [55 - 70] Pages: 16

DOI: 10.2174/1871523017666181116092934

Abstract

Background: Rheumatoid Arthritis (RA) is a devastating disease characterized by continual addition of leukocytes and T cells within the articular cavity causing inflammation and cartilage destruction. Withania somnifera is one of the most precious medicinal herbs, reported to have antioxidant, anti‐inflammatory, and immunomodulatory properties.

Objective: The purpose of this study was to evaluate anti-inflammatory activity of aqueous extract of Withania somnifera roots (WSAq) in Collagen Induced Arthritic (CIA) rats.

Methods: To achieve this, we assessed the level of inflammatory cytokines such as Tumor Necrosis Factor (TNF)-α, IL-1β, IL-6 and IL-10 in CIA rats. Further, transcription factor, oxidative stress parameters and CD+8 expressions were also analyzed in CIA rats.

Results: Arthritic rats showed a greater increase in the levels of pro inflammatory cytokines such as TNF-α, IL-1β, IL-6, transcription factor NF-κB and a decrease in IL-10 concentration than controls rats. Oral administration of WSAq at a dose of 300mg/kg.wt. (WSAq300) appreciably attenuated the production of these pro inflammatory cytokines. This anti-inflammatory activity of WSAq300 might be partly mediated through an increase in the secretion of IL-10 and inhibition of NF-κB activity. Further, arthritic rats also show increased oxidative stress as compared to control rats. This increased oxidative stress in the arthritic rats appears to be the outcome of both an activated pro-oxidant and a poor antioxidant defense system. Treatment with WSAq300 strongly ameliorates all these ROS parameters significantly to near normal. Additional, metalloproteinase MMP-8 levels were also measured and found to be increased in CIA rats, which after treatment with WSAq300 came down to near normal.

Conclusion: From the above results, it can be concluded that the use of WSAq300 may be a valuable supplement which can improve human arthritis.

Keywords: Collagen induced arthritis, inflammation, joint destruction, oxidative stress, rheumatoid arthritis, Withania somnifera.

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[1]
Scott, D.L.; Wolfe, F.; Huizinga, T.W. Rheumatoid arthritis. Lancet, 2010, 376(9746), 1094-1108.
[2]
Carson, D.A.; Chen, P.P.; Kipps, T.J. New roles for rheumatoid factor. J. Clin. Invest., 1991, 87(2), 379-383.
[3]
Komatsu, N.; Takayanagi, H. Inflammation and bone destruction in arthritis: Synergistic activity of immune and mesenchymal cells in joints. Front. Immunol., 2012, 3, 77.
[4]
Matsuno, H.; Yudoh, K.; Katayama, R.; Nakazawa, F.; Uzuki, M.; Sawai, T.; Yonezawa, T.; Saeki, Y.; Panayi, G.S.; Pitzalis, C.; Kimura, T. The role of TNF-alpha in the pathogenesis of inflammation and joint destruction in Rheumatoid Arthritis (RA): A study using a human RA/SCID mouse chimera. Rheumatology (Oxford), 2002, 41(3), 329-337.
[5]
Boyle, W.J.; Simonet, W.S.; Lacey, D.L. Osteoclast differentiation and activation. Nature, 2003, 423(6937), 337-342.
[6]
Kamanli, A.; Naziroğlu, M.; Aydilek, N.; Hacievliyagil, C. Plasma lipid peroxidation and antioxidant levels in patients with rheumatoid arthritis. Cell Biochem. Funct., 2004, 22(1), 53-57.
[7]
Seven, A.; Güzel, S.; Aslan, M.; Hamuryudan, V. Lipid, protein, DNA oxidation and antioxidant status in rheumatoid arthritis. Clin. Biochem., 2008, 41(7-8), 538-543.
[8]
Griffiths, H. Is the generation of neo-antigenic determinants by free radicals central to the development of autoimmune rheumatoid disease? Autoimmun. Rev., 2008, 7(7), 544-549.
[9]
Luo, X.; Zuo, X.; Mo, X.; Zhou, Y.; Xiao, X. Treatment with recombinant Hsp72 suppresses collagen-induced arthritis in mice. Inflammation, 2011, 34(5), 432-439.
[10]
Gerlag, D.M.; Ransone, L.; Tak, P.P.; Han, Z.; Palanki, M.; Barbosa, M.S.; Boyle, D.; Manning, A.M.; Firestein, G.S. The effect of a T cell-specific NF-kappa B inhibitor on in vitro cytokine production and collagen-induced arthritis. J. Immunol., 2000, 165(3), 1652-1658.
[11]
Roth, S.H. Coming to terms with nonsteroidal anti-inflammatory drug gastropathy. Drugs, 2012, 72(7), 873-879.
[12]
Schiff, M.; Keiserman, M.; Codding, C.; Songcharoen, S.; Berman, A.; Nayiager, S.; Saldate, C.; Aranda, R.; Becker, J.C.; Nys, M.; Bars, M.L.; Reed, D.M.; Poncet, C.; Dougados, M. Clinical response and tolerability to abatacept in patients with rheumatoid arthritis previously treated with infliximab or abatacept: Open label extension of the ATTEST Study. Ann. Rheum. Dis., 2011, 70(11), 2003-2007.
[13]
Abdel-Tawab, M.; Werz, O.; Schubert-Zsilavecz, M. Boswellia serrata: An overall assessment of in vitro, preclinical, pharmacokinetic and clinical data. Clin. Pharmacokinet., 2011, 50(6), 349-369.
[14]
Cronstein, B.N. The mechanism of action of methotrexate. Rheum. Dis. Clin. North Am., 1997, 23(4), 739-755.
[15]
Dar, N.J.; Hamid, A.; Ahmad, M. Pharmacologic overview of Withania somnifera, the Indian Ginseng. Cell. Mol. Life Sci., 2015, 72(23), 4445-4460.
[16]
Gao, R.; Shah, N.; Lee, J.S.; Katiyar, S.P.; Li, L.; Oh, E.; Sundar, D.; Yun, C.O.; Wadhwa, R.; Kaul, S.C. Withanone-rich combination of Ashwagandha withanolides restricts metastasis and angiogenesis through hnRNP-K. Mol. Cancer Ther., 2014, 13(12), 2930-2940.
[17]
Ichikawa, H.; Takada, Y.; Shishodia, S.; Jayaprakasam, B.; Nair, M.G.; Aggarwal, B.B. Withanolides potentiate apoptosis, inhibit invasion, and abolish osteoclastogenesis through suppression of nuclear factor-kappaB (NF-kappaB) activation and NF-kappaB-regulated gene expression. Mol. Cancer Ther., 2006, 5(6), 1434-1445.
[18]
Campo, G.M.; Avenoso, A.; Campo, S.; Ferlazzo, A.M.; Altavilla, D.; Calatroni, A. Efficacy of treatment with glycosaminoglycans on experimental collagen-induced arthritis in rats. Arthritis Res. Ther., 2003, 5(3), R122-R131.
[19]
Hultqvist, M.; Olofsson, P.; Gelderman, K.A.; Holmberg, J.; Holmdahl, R. A new arthritis therapy with oxidative burst inducers. PLoS Med., 2006, 3(9), e348.
[20]
Holmdahl, R.; Carlsen, S.; Mikulowska, A.; Vestberg, M.; Brunsberg, U.; Hansson, A.; Sunduall, M.; Jansson, L.; Pettersson, U. Genetic analysis of murine models for rheumatoid arthritis. In: Adolpho KW (ed.). Human Genome Methods; New York: CRC Press, 1998, pp. 215-238.
[21]
Schmittgen, T.D.; Zakrajsek, B.A.; Mills, A.G.; Gorn, V.; Singer, M.J.; Reed, M.W. Quantitative reverse transcription-polymerase chain reaction to study mRNA decay: Comparison of endpoint and real-time methods. Anal. Biochem., 2000, 285(2), 194-204.
[22]
Zhang, L.; Sun, T.; Yu, E.; Yu, L.; Luo, J.; Li, H.; Fu, Z. TNF -α expression, not iNOS expression, is correlated with NF-B activation in the spinal cord of rats following peripheral nerve injury. Afr. J. Biotechnol., 2011, 10(34), 6372-6380.
[23]
Khan, M.S.; Halagowder, D.; Devaraj, S.N. Methylat-ed chrysin induces co-ordinated attenuation of the canonical Wnt and NF-κB signaling pathway and upregulates apoptotic gene expression in the early hepatocarcinogenesis rat model. Chem. Biol. Interact., 2011, 193(1), 12-21.
[24]
Adán, N.; Guzmán-Morales, J.; Ledesma-Colunga, M.G.; Perales-Canales, S.I.; Quintanar-Stéphano, A.; López-Barrera, F.; Méndez, I.; Moreno-Carranza, B.; Triebel, J.; Binart, N. Martínez, de. La.; Escalera. G.; Thebault, S.; Clapp, C. Prolactin promotes carti-lage survival and attenuates inflammation in in-flammatory arthritis. J. Clin. Invest., 2013, 123(9), 3902-3913.
[25]
Deschner, J.; Rath-Deschner, B.; Agarwal, S. Regulation of matrix metalloproteinase expression by dynamic tensile strain in rat fibrochondrocytes. Osteoarthritis Cartilage, 2006, 14(3), 264-272.
[26]
Azizian, M.; Bathaie, S.Z.; Ashrafi, M.; Hoshyar, R. Investigation of p53 and p27 expressions in the N-nitroso-N-methylureainduced breast cancer in female Wistar Albino rats. Physiol. Pharmacol., 2014, 18(3), 337-346.
[27]
Shimozuru, Y.; Yamane, S.; Fujimoto, K.; Terao, K.; Honjo, S.; Nagai, Y.; Sawitzke, A.D.; Terato, K. Collagen-induced arthritis in nonhuman primates: multiple epitopes of type II collagen can induce autoimmune-mediated arthritis in outbred cynomolgus monkeys. Arthritis Rheum., 1998, 41(3), 507-514.
[28]
Horsfall, A.C.; Butler, D.M.; Marinova, L.; Warden, P.J.; Williams, R.O.; Maini, R.N.; Feldmann, M. Suppression of collagen-induced arthritis by continuous administration of IL-4. J. Immunol., 1997, 159(11), 5687-5696.
[29]
Morel, J.; Berenbaum, F. Signal transduction pathways: New targets for treating rheumatoid arthritis. Joint Bone Spine, 2004, 71(6), 503-510.
[30]
Tu, S.; Hu, Y.; Zeng, K.; Zhang, M.; Lai, X.; Weichen, Z. Effects of triptolide on the expression and activity of NF-kappaB in synovium of collagen-induced arthritis rats. J. Huazhong Univ. Sci. Technolog. Med. Sci., 2005, 25(5), 543-545.
[31]
Maitra, R.; Porter, M.A.; Huang, S.; Gilmour, B.P. Inhibition of NFkappaB by the natural product Withaferin A in cellular models of Cystic Fibrosis inflammation. J. Inflamm. (Lond.), 2009, 6, 15.
[32]
Young, C.L.; Adamson, T.C.; Vaughan, J.H.; Fox, R.I. Immunohistologic characterization of synovial membrane lymphocytes in rheumatoid arthritis. Arthritis Rheum., 1984, 27(1), 32-39.
[33]
Kang, Y.M.; Zhang, X.; Wagner, U.G.; Yang, H.; Beckenbaugh, R.D.; Kurtin, P.J.; Goronzy, J.J.; Weyand, C.M. CD8 T cells are required for the formation of ectopic germinal centers in rheumatoid synovitis. J. Exp. Med., 2002, 195(10), 1325-1336.
[34]
Filippin, L.I.; Vercelino, R.; Marroni, N.P.; Xavier, R.M. Redox signalling and the inflammatory response in rheumatoid arthritis. Clin. Exp. Immunol., 2008, 152(3), 415-422.
[35]
Morel, J.; Berenbaum, F. Signal transduction pathways: New targets for treating rheumatoid arthritis. Joint Bone Spine, 2004, 71(6), 503-510.
[36]
Hashizume, M.; Mihara, M. The roles of interleukin-6 in the pathogenesis of rheumatoid arthritis. Arthritis, 2011, 2011, 765624.
[37]
Schottelius, A.J.; Mayo, M.W.; Sartor, R.B.; Baldwin, A.S., Jr Interleukin-10 signaling blocks inhibitor of kappaB kinase activity and nuclear factor kappaB DNA binding. J. Biol. Chem., 1999, 274(45), 31868-31874.
[38]
Mazzetti, I.; Grigolo, B.; Borzì, R.M.; Meliconi, R.; Facchini, A. Serum copper/zinc superoxide dismutase levels in patients with rheumatoid arthritis. Int. J. Clin. Lab. Res., 1996, 26(4), 245-249.
[39]
Pandey, K.B.; Rizvi, S.I. Markers of oxidative stress in erythrocytes and plasma during aging in humans. Oxid. Med. Cell. Longev., 2010, 3(1), 2-12.
[40]
Dieterich, S.; Bieligk, U.; Beulich, K.; Hasenfuss, G.; Prestle, J. Gene expression of antioxidative enzymes in the human heart: Increased expression of catalase in the end-stage failing heart. Circulation, 2000, 101(1), 33-39.
[41]
Khan, M.A.; Subramaneyaan, M.; Arora, V.K.; Banerjee, B.D.; Ahmed, R.S. Effect of Withania somnifera (Ashwagandha) root extract on amelioration of oxidative stress and autoantibodies production in collagen-induced arthritic rats. J. Complement. Integr. Med., 2015, 12(2), 117-125.

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