Chamazulene reverses osteoarthritic inflammation through regulation of matrix metalloproteinases (MMPs) and NF-kß pathway in in-vitro and in-vivo models.

ABSTRACT

This study was conducted to evaluate the protective effects of chamazulene against IL-1ß-induced rat primary chondrocytes and complete Freund's adjuvant (CFA)-induced osteoarthritic inflammation in rats. Oxidative stress markers, pro-inflammatory cytokines, and regulatory proteins were measured. Chamazulene significantly reverted (p < 0.05) the levels of lipid peroxidation and enhanced the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) enzymes against IL-1ß and CFA-induced oxidative stress. The levels of TNF-α and IL-6 were reduced (p < 0.05) in chamazulene treatment against IL-1ß and CFA-induced inflammation. Western blot analysis results on the expressions of MMP-3, MMP-9, p65 NF-kß, iNOS, and COX-2 showed chamazulene was able to protect the chondrocytes against IL-1ß-induced osteoarthritic inflammation. Histopathology of rat hind ankle showed chamazulene significantly protected against CFA-induced osteoarthritic inflammation. Therefore, chamazulene can be recommended as a therapeutic agent for clinical trials against osteoarthritic inflammation.