High fructose is considered a causative factor for oxidative stress and autophagy imbalance that cause kidney pathogenesis. Antioxidant polydatin isolated from Polygonum cuspidatum has been reported to protect against kidney injury. In this study, polydatin was found to ameliorate fructose-induced podocyte injury. It activated mammalian target of rapamycin complex 1 (mTORC1) and suppressed autophagy in glomeruli of fructose-fed rats and in fructose-exposed conditionally immortalized human podocytes (HPCs). Polydatin also enhanced nuclear factor-E2-related factor 2 (Nrf2)-dependent antioxidant capacity to suppress fructose-induced autophagy activation in vivo and in vitro, with the attenuation of fructose-induced up-regulation of cellular light chain 3 (LC3) II/I protein levels. This effect was abolished by Raptor siRNA in fructose-exposed HPCs. These results demonstrated that polydatin ameliorated fructose-induced autophagy imbalance in an mTORC1-dependent manner via improving Nrf2-dependent antioxidant capacity during podocyte injury. In conclusion, polydatin with anti-oxidation activity suppressed autophagy to protect against fructose-induced podocyte injury.

高果糖被认为是导致肾脏发病机制的氧化应激和自噬失衡的致病因素。据报道，从虎杖中分离出的抗氧化剂虎杖苷可防止肾损伤。在这项研究中，虎杖苷被发现可以改善果糖诱导的足细胞损伤。它激活雷帕霉素复合物 1 (mTORC1) 的哺乳动物靶点并抑制果糖喂养大鼠肾小球和果糖暴露条件性永生化人足细胞 (HPC) 中的自噬。虎杖苷还增强了核因子 E2 相关因子 2 (Nrf2) 依赖性抗氧化能力，从而在体内和体外抑制果糖诱导的自噬激活，随着果糖诱导的细胞轻链 3 (LC3) II/I 蛋白水平上调的减弱。在暴露于果糖的 HPC 中，Raptor siRNA 消除了这种效应。这些结果表明虎杖苷通过改善足细胞损伤期间依赖 Nrf2 的抗氧化能力，以依赖 mTORC1 的方式改善果糖诱导的自噬失衡。总之，具有抗氧化活性的虎杖苷抑制自噬以防止果糖诱导的足细胞损伤。