安石榴苷通过激活自噬抑制软骨细胞凋亡和ECM降解治疗骨关节炎

Abstract

Background Osteoarthritis (OA) is a prevalent articular disorder and has no entirely satisfactory treatment. Punicalagin (PUG) is a polyphenol which has shown multiple pharmacological effects on various diseases. However, the role of PUG in the treatment of OA has not been well defined.Methods The effects of PUG on anti-oxidative stress, anti-apoptosis, extracellular matrix (ECM) degradation and autophagy were evaluated in chondrocytes through Western blot and immunofluorescence (IF) staining. Meanwhile, the effects of PUG on destabilization of the medial meniscus (DMM) model were also assessed in vivo by performing histopathologic analysis and IF staining.Results In vitro, PUG treatment not only increased the level of HO-1 and SOD1 against oxidative stress but also suppressed the expression of apoptotic proteins and inhibited ECM degradation. Meanwhile, PUG treatment activated autophagy and restores autophagic flux in chondrocytes after tert-butyl hydroperoxide (TBHP) insult, inhibition of autophagy by 3-methyladenine (3-MA) partly abrogated the protective effects of PUG on chondrocytes. In vivo, degeneration of the articular cartilage following DMM was also ameliorated by PUG treatment.Conclusion PUG prevents the progression of OA through inhibition of apoptosis, oxidative stress and ECM degradation in chondrocytes, which mediated by the activation of autophagy.