Cyanidin‐3‐glucoside protects against high glucose‐induced injury in human nucleus pulposus cells by regulating the Nrf2/HO‐1 signaling

Abstract Cyanidin‐3‐glucoside (C3G) is a well‐known natural anthocyanin with antioxidant and anti‐inflammatory properties. In this study, we explored the role and action mechanism of C3G in high glucose (HG)‐induced damage of human nucleus pulposus cells (HNPCs). Cell viability was assessed by CCK‐8 assay. TUNEL assay was performed for detecting apoptotic rate. Western blot was performed to determine the expression levels of cl‐caspase‐3, caspase‐3, Bax, Bim, collagen II, aggrecan, MMP‐3, MMP‐13, and ADAMTS5. Reactive oxygen species (ROS) generation was analyzed using DCFH‐DA staining. The Nrf2 was knocked down or overexpressed in HNPCs through transfection with si‐Nrf2 or pcDNA3.0‐Nrf2. C3G treatment (12.5, 25, and 50 μM) improved cell viability of HNPCs under HG condition. HG‐induced cell apoptosis of HNPCs was attenuated by C3G with decreased apoptotic rate and relative levels of cl‐caspase‐3/caspase‐3, Bax, and Bim. C3G treatment caused significant increase in expression levels of collagen II and aggrecan and decrease in the relative levels of MMP‐3, MMP‐13, and ADAMTS5. After treatment with C3G, ROS generation in HNPCs was markedly reduced. Treatment with N ‐acetylcysteine (NAC) reversed HG‐induced cell apoptosis and extracellular matrix (ECM) degradation. C3G treatment induced the expression of Nrf2 and HO‐1 in HG‐induced HNPCs. Moreover, knockdown of Nrf2 reversed the inhibitory effect of C3G on ROS production. Summarily, C3G exerted a protective effect on ROS‐mediated cellular damage in HNPCs under HG condition, which was attributed to the induction of the Nrf2/HO‐1 signaling pathway.