Potential of Topical Curcumin in Reduction of TNF-α expression and Synovium Hyperplasia on Wistar Rats of Rheumatoid Arthritis Model

Ferri Widodo, Diana Lyrawati, Bagus Putu Putra Suryana


Rheumatoid arthritis is a chronic inflammatory autoimmune disease associated with articular and systemic effects. This disease affects synovial joints covered by a special tissue called synovium. Curcumin has a potent antioxidant, antiinflammatory agent, antiangiogenic and anticarcinogenic. Curcumin can downregulate the expression of various proinflammatory cytokines and is reported beneficial effects in arthritis, but has a poor solubility dan bioavailability as well. The purpose of this research was to study the potential of liposomes topikal curcumin in reducing athritis score, reducing the expression of TNF-α and histopathological synovium hyperplasia of hind paw on Wistar rats with CFA that had been treated with topical curcumin. In this study, rats were divided into 7 groups: positive control, negative control, rheumatoid arthritis with topical curcumin therapy of 90 mg/kg BW, rheumatoid arthritis with topical curcumin therapy of 110 mg/kg BW, rheumatoid arthritis with topical curcumin therapy of 200 mg/kg BW, rheumatoid arthritis with methotrexate therapy, rheumatoid arthritis with placebo therapy. Results from this experiment indicated that topical curcumin has no significant to the arthritis score, significantly effect to percentase expression of TNF-α (p<0.05) and could decrease synovium hyperplasia based on histophatology examination. It could be concluded that therapy of topical curcumin could decrease the expression of TNF- α and synovium hyperplasia in rheumatoid arthritis rat.



Arthritis; CFA; Curcumin; TNF-α; Synovium Hyperplasia

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Anand, e. a. (2007). Bioavailability of Curcumin: Problems and Promises. Molecular Pharmaceutics, 4(6), 807-818. doi: 10.1021/mp700113r

Banda, N. K., Levitt, B., Glogowska, M. J., Thurman, J. M., Takahashi, K., Stahl, G. L., Holers, V. M. (2009). Targeted inhibition of the complement alternative pathway with complement receptor 2 and factor H attenuates collagen antibody-induced arthritis in mice. The Journal of Immunology, 183(9), 5928-5937.

Bevaart, L., Vervoordeldonk, M. J., & Tak, P. P. (2010). Evaluation of therapeutic targets in animal models of arthritis: How does it relate to rheumatoid arthritis? Arthritis & Rheumatism, 62(8), 2192-2205. doi: 10.1002/art.27503

Borashan, F. A., Ilkhanipoor, M., Hashemi, M., & Farrokhi, F. (2009). Investigation the effects of curcumin on serum hepatic enzymes activity in a rheumatoid arthritis model. Electronic Journal of Biology, 4(4), 129-133.

Choy, E. H. S., & Panayi, G. S. (2001). Cytokine Pathways and Joint Inflammation in Rheumatoid Arthritis. New England Journal of Medicine, 344(12), 907-916. doi: doi:10.1056/ NEJM200103223441207

Choy, E. (2012). Understanding the dynamics: pathways involved in the pathogenesis of rheumatoid arthritis. Rheumatology, 51(suppl 5), v3-v11. doi: 10.1093/rheumatology/kes113

Chu, K., Zheng, H., Li, H., Zhang, Y., Zhang, X., Xu, W., & Chen, L. (2013). Shuangtengbitong tincture treatment of collagen‑induced arthritis via downregulation of the expression of IL-6, IL-8, TNF-α and NF-κB. Experimental and therapeutic medicine, 5(2), 423-428.

Gaujoux-Viala, C., Nam, J., Ramiro, S., Landewé, R., Buch, M. H., Smolen, J. S., & Gossec, L. (2014). Efficacy of conventional synthetic disease-modifying antirheumatic drugs, glucocorticoids and tofacitinib: a systematic literature review informing the 2013 update of the EULAR recommendations for management of rheumatoid arthritis. Annals of the Rheumatic Diseases, 73(3), 510-515. doi: 10.1136/annrheumdis-2013-204 588

Goel, A., Kunnumakkara, A. B., & Aggarwal, B. B. (2008). Curcumin as “Curecumin”: From kitchen to clinic. Biochemical Pharmacology, 75(4), 787-809.doi:http://dx.doi.org/10.1016/j.bcp.2007.08.016

Green, E. A., & Flavell, R. A. (2000). The Temporal Importance of TNFα Expression in the Development of Diabetes. Immunity, 12(5), 459-469. doi: http://dx.doi.org/10.1016/S1074-7613 (00)80198-3

Harbuz, M., Perveen-Gill, Z., Lalies, M., Jessop, D., Lightman, S., & Chowdrey, H. (1996). The role of endogenous serotonin in adjuvant-induced arthritis in the rat. Rheumatology, 35(2), 112-116.

Jagetia, G., & Aggarwal, B. (2007). “Spicing Up” of the Immune System by Curcumin. Journal of Clinical Immunology, 27(1), 19-35. doi: 10.1007/ s10875-006-9066-7

Kapoor, B., Singh, S. K., Gulati, M., Gupta, R., & Vaidya, Y. (2014). Application of Liposomes in Treatment of Rheumatoid Arthritis: Quo Vadis. The Scientific World Journal, 2014, 17. doi: 10.1155/2014/978351

Kaur, G., & Sultana, S. (2012). Evaluation of antiarthritic activity of isoeugenol in adjuvant induced arthritis in murine model. Food Chem Toxicol, 50(8), 2689-2695. doi: 10.1016 /j.fct.2012.05.016

Kim, H. R., Cho, M. L., Kim, K. W., Juhn, J. Y., Hwang, S. Y., Yoon, C. H., . . . Kim, H. Y. (2007). Up-regulation of IL-23p19 expression in rheumatoid arthritis synovial fibroblasts by IL-17 through PI3-kinase-, NF-kappaB- and p38 MAPK-dependent signalling pathways. Rheumatology (Oxford), 46(1), 57-64. doi: 10.1093/rheumatology/kel159

Moon, D. O., Kim, M. O., Choi, Y. H., Park, Y. M., & Kim, G. Y. (2010). Curcumin attenuates inflammatory response in IL-1beta-induced human synovial fibroblasts and collagen-induced arthritis in mouse model. Int Immunopharmacol, 10(5), 605-610. doi: 10.1016/j.intimp.2010.02.011

Nainggolan, O. (2009). Prevalence and Determinant of Arthritis in Indonesia. Maj Kedokt Indon, 59, 589-594.

Sahebari M, e. a. (2011). Inhibitory effect of aqueous extract of saffron (crocus sativus L.) on adjuvant induced arthritis in wistar rat. Pharmacologyonline, 3, 802-808.

Simadibrata, M. (2004). Gastrointestinal tract disorder as a side effect of non-steroidal anti inflammatory drugs (NSAIDs). Acta Med Indones, 36, 195-196.

Sonavane, K., Phillips, J., Ekshyyan, O., Moore-Medlin, T., Roberts Gill, J., Rong, X., Nathan, C.-A. O. (2012). Topical Curcumin-Based Cream Is Equivalent to Dietary Curcumin in a Skin Cancer Model. J Skin Cancer, 2012, 9. doi: 10.1155/2012/147863

Sooriakumaran, P. (2006). COX-2 inhibitors and the heart: are all coxibs the same? Postgrad Med J, 82(966), 242-245. doi: 10.1136/pgmj.2005. 042234

Suwito, M., Handono, K., Kalim, H., Suryana, B., & Wahono, C. (2010). Correlation between anti-cyclic citrulinated peptide antibodies and the severity of clinical manifestation, laboratory manifestation, and radiological joint destruction in rheumatoid arthritis patients. Indonesian Journal of Rheumatology, 02(1), 14-17.

Thanusubramanian, H., Thanusubramanian, A., V, M. B., Kumari, Meena, & Kishore, K. (2014). Biologics: Role in rheumatoid arthritis. World Journal of Pharmaceutical Research, 3(7), 746-754.

Volin, M. V., & Koch, A. E. (2000). Cell cycle implications in the pathogenesis of rheumatoid arthritis. Frontiers in Bioscience, 5, d594-601.

Wu, M., Zeng, F., Wang, R., Seto, W., & Pai, P. (2013). Atherosclerosis in Patients with Rheumatoid Arthritis. Rheumatol Curr Res S5: 002. doi: 10.4172/2161-1149. S5-002 Page 2 of 7 Rheumatol Curr Res ISSN: 2161-1149 Rheumatology, an open access journal Atherosclerosis and Rheumatic Diseases clinical importance for the presence of carotid plaque, but not carotid IMT, was demonstrated by a study involving 105 patients with RA, that demonstrated patients with bilateral carotid plaques were associated with a worse CVD event survival (Hazard ratio= 6.31)[24]. These result confirmed that RA is strongly associated with atherosclerosis development in the carotid arteries that could explain for the high stroke incidence in these patients.

Youn, J., Kim, H. Y., Park, J. H., Hwang, S. H., Lee, S. Y., Cho, C. S., & Lee, S. K. (2002). Regulation of TNF-alpha-mediated hyperplasia through TNF receptors, TRAFs, and NF-kappaB in synoviocytes obtained from patients with rheumatoid arthritis. Immunol Lett, 83(2), 85-93.

Young, J, D., N, C., P, D., J, D., P, E., J, W. (2000). How does functional disability in early rheumatoid arthritis (RA) affect patients and their lives? Results of 5 years of follow-up in 732 patients from the Early RA Study (ERAS). Rheumatology, 39(6), 603-611.

Zahidah. (2012). Curcumin as an Anti-Arthritic Agent in Collagen-Induced Arthritic Sprague-Dawley Rats. Sains Malaysiana, 41(5), 591-595.

DOI: https://doi.org/10.21776/ub.rjls.2016.003.01.6


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