Can curcuminoids be more effective than sulfasalazine for the treatment of rheumatoid arthritis?

Shaikh, Murassa (2018) Can curcuminoids be more effective than sulfasalazine for the treatment of rheumatoid arthritis? Doctoral thesis, University of Central Lancashire.

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Abstract

Rheumatoid Arthritis (RA) is a debilitating, chronic autoimmune disease leading to progressive joint destruction. Current treatment includes methotrexate and sulfasalazine, however, side effects and tolerability are major limitations. Curcumin is a natural polyphenol obtained from Curcuma Longa (turmeric) that exhibits potent anti-rheumatic properties. In this study, column chromatography and preparative thin layer chromatography (PTLC) were successfully used for the isolation of 1.1747 g curcumin from turmeric. RP-HPLC method was used for monitoring the stability of curcumin and sulfasalazine following ICH guidelines. The method used was found to be linear, precise (%RSD ≤2) and accurate with good repeatability and reproducibility. Forced degradation studies demonstrated that sulfasalazine was relatively stable under stressed conditions, culminating to approximately 80-90% recovery whereas curcumin degraded completely after 60 days. At high temperatures, both compounds exhibited degradation.
The therapeutic efficacy of curcumin, DMC, BDMC, methotrexate and sulfasalazine was investigated on inflammatory response genes, COL14A1, CXCL12, CYTL1, HSPA6, IFTIM1, IL-6, IL-7, MMP-1, MMP-13 and TNFSF10 that were previously identified following microarray analysis. Human Fibroblast-like Synoviocytes isolated from RA patients (HFLS-RA) were treated with the IC50 (inhibitory concentration) of the compounds and subjected to qRT-PCR analysis for measuring the expression profile of the candidate genes. CRP ELISA assay was used to confirm the findings for IL-6 gene expression in untreated and treated conditions. Curcumin exhibited increased potency in downregulating gene expression in comparison to the other treatments. Therefore, the potential use of curcumin in conjunction with the current therapies would minimise the side effects and significantly improve the outcome and quality of life for RA patients.


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