Andrographolide Benefits Rheumatoid Arthritis via Inhibiting MAPK Pathways

Andrographolide (AD) is the main compound distributed in medicinal herb Andrographis paniculata and exhibits anti-inflammatory activity. AD has been used for the treatment of multiple inflammatory diseases. However, the therapeutic value of AD on human rheumatoid arthritis (RA) remains unclear. In this study, we investigated the effects of AD on collagen-induced arthritis (CIA) and human RA synovial fibroblasts (RA-SFs). CIA mice were treated with AD (dissolved in 0.5% CMC-Na, 100 mg/kg per day) or vehicle (0.5% CMC-Na) daily by oral gavage for 2 weeks. The arthritis severity and joint destruction were assessed. Serum anti-collagen II antibody (anti-CII Abs) and cytokines were determined by ELISA. TNF alpha-stimulated human RA-SFs were treated with varying doses of AD for in vitro investigation. Results showed that AD significantly attenuated the arthritis severity and joint damage. AD treatment significantly reduced the production of serum anti-CII, TNF alpha, IL-1 beta, and IL-6. In vitro, AD decreased the secretion of IL-1 beta and IL-6 from TNF alpha-stimulated RA-SFs in a dose-dependent manner. AD treatment reduced the TNF alpha-induced phosphorylation of p38 MAPK and ERK1/2 in a dose-dependent manner. Thus, our findings suggest that AD confers protective effects on autoimmune arthritis through inhibiting MAPK pathways.