Chlorogenic acid protects human chondrocyte C28/I2 cells from oxidative stress-induced cell death through activation of autophagy.

Abstract Aims The development of osteoarthritis (OA), the most common form of arthritis, is commonly associated with oxidative stress. Indeed, the lack of antioxidant responses largely increases OA incidence. OA is a leading cause of disability in the elderly, which reduces the quality of life and places high socioeconomic burdens on them. Several polyphenolic compounds, including chlorogenic acid (CGA), have shown cytoprotective effects via their antioxidant activity, but the exact mechanism (s) remain elusive. In this study, we demonstrated how CGA protects human chondrocytes against H2O2-induced apoptosis. Materials and methods The cytoprotective effect by CGA in 500 μM hydrogen peroxide-treated C28/I2 cells was evaluated by cell viability, TUNEL assay, and Western blotting analyses, and autophagy assessment was further performed by AO and MDC staining and tandem mRFP-GFP fluorescence analyses. Key findings Treatment of CGA to the human chondrocytes under oxidative stress significantly decreased apoptosis markers, such as cleaved caspase 3 and cleaved PARP, and increased anti-apoptotic marker Bcl-xL and the antioxidant response proteins NRF2 and NF-κB. Furthermore, CGA-dependent activation of antioxidant response proteins NRF2 and NF-κB and its protective effects in chondrocytes depended on autophagy. Indeed, CGA treatment and autophagy induction significantly decreased reactive oxygen species (ROS)–induced apoptosis. Significance CGA exhibited the protective effect to human chondrocyte C28/I2 cells against oxidative stress-induced cell death by activating autophagy. These findings indicate that CGA is a potential therapeutic agent for the development of OA drugs.