A novel combination of methotrexate and epigallocatechin attenuates the overexpression of pro-inflammatory cartilage cytokines and modulates antioxidant status in adjuvant arthritic rats

Abstract

The present study was designed to evaluate the combinatory effect of methotrexate (MTX) and epigallocatechin (EGCG) on the progression of adjuvant-induced arthritis in rats. Adjuvant arthritis (AA) was induced by a single intradermal injection of Freund's complete adjuvant. AA rats were treated with methotrexate (0.3 mg/kg) thrice a week, EGCG (100 mg/kg) daily, and combination of MTX and EGCG thrice a week for a period of 28 days. Paw swelling changes and histopathological and radiographic analysis was assessed to evaluate the antiarthritic effect. Lipid peroxidation and antioxidant enzyme activities in joint tissue homogenate were performed to observe the modulation of antioxidant status along the expression of different pro-inflammatory cartilage cytokines like TNF-α and IL-6. MTX and EGCG combination potentiated both the antiarthritic (decrease of hind paw volume) and the antioxidant effect (SOD, GSH, and catalase) as well as suppression of lipid peroxidation. Combination therapy of MTX and EGCG significantly inhibited the development phase of arthritis, which is supported by histopathological, radiographical, and attenuation of overexpression of cartilage cytokines. EGCG act as potent antioxidant and immunomodulator, suggesting that combined administration of MTX along with EGCG suppressed the development phase of arthritic progression in rats.