Salidroside, A Natural Antioxidant, Improves β-Cell Survival and Function via Activating AMPK Pathway

Aim: The enhanced oxidative stress contributes to progression of type 2 diabetes mellitus (T2DM) and induces beta-cell failure. Salidroside is a natural antioxidant extracted from medicinal food plant Rhodiola rosea. This study was aimed to evaluate protective effects of salidroside on beta-cells against diabetes associated oxidative stress. Methods and Results: In diabetic db/db and high-fat diet-induced mice, we found salidroside ameliorated hyperglycemia and relieved oxidative stress. More importantly, salidroside increased beta-cell mass and beta-cell replication of diabetic mice. Mechanism study in Min6 cells revealed that, under diabetic stimuli, salidroside suppressed reactive oxygen species production and restore mitochondrial membrane potential (1 9 m) via reducing NOX2 expression and inhibiting JNK-caspase 3 apoptotic cascade subsequently to protect beta-cell survival. Simultaneously, diabetes associated oxidative stress also activated FOXO1 and triggered nuclear exclusion of PDX1 which resulted in beta-cell dysfunction. This deleterious result was reversed by salidroside by activating AMPK-AKT to inhibit FOXO1 and recover PDX1 nuclear localization. The efficacy of salidroside in improving beta-cell survival and function was further confirmed in isolated cultured mouse islets. Moreover, the protective effects of salidroside on beta-cells against diabetic stimuli can be abolished by an AMPK inhibitor compound C, which indicated functions of salidroside on beta-cells were AMPK activation dependent. Conclusion: These results confirmed beneficial metabolic effects of salidroside and identified a novel role for salidroside in preventing beta-cell failure via AMPK activation. Our finding highlights the potential value of Rhodiola rosea as a dietary supplement for diabetes control.