Phytomolecule Epimedin C Mitigates Cartilage Extracellular Matrix Degradation and Osteoarthritis Progression in Rats

Abstract Osteoarthritis (OA) is a common degenerative joint disease associated with chronic inflammation. Epimedin C (EpiC), flavonoid from Epimedin, enhances the extracellular matrix (ECM) expression in human chondrocytes in vitro. This study aims to investigate the effects of EpiC on osteoarthritis progress in vivo. OA is induced in Lewis rats by medial meniscus transection and treatment with intra‐articular injections of EpiC. EpiC treatment reduces joint swelling and improves hindlimb weight distribution in MMT‐induced OA rats. Pathological changes in cartilage are observed and evaluated by the osteoarthritis research society international (OARSI) score and both EpiC groups have lower OARSI scores than the OA group. The EpiC groups also exhibit higher positive expressions of collagen II and aggrecan, and lower MMP13 and ADAMTS5 in the cartilage. RNA‐seq suggest that EpiC may attenuate MMT‐induced ECM degradation by inhibiting the JAK‐STAT pathway. EpiC promotes the gene expressions of Col2a1 and Acan, while inhibiting Mmp13 and Col10a1 in cartilage. EpiC reduces the phosphorylated STAT3 in human chondrocyte pellets stimulated with inflammatory cytokines. In conclusion, EpiC demonstrates potential as an OA therapeutic by reducing pain and ECM degradation through p‐STAT3 inhibition.