Coptisine protects against hyperuricemic nephropathy through alleviating inflammation, oxidative stress and mitochondrial apoptosis via PI3K/Akt signaling pathway

作者：Yanlu Liu, Shiting Gong, Kejian Li, Wu Gong, Xiaohong Zheng, Jingna Zheng, Xiaowei Lu, Luyao Zhang, Jincan Li, Ziren Su, Yuhong Liu, Jianhui Xie, Jiannan Chen, Yucui Li · 发表于：Biomedicine & Pharmacotherapy · 年份：2022 · DOI：10.1016/j.biopha.2022.113941 · 被引用次数：113 · 研究领域：Gout, Hyperuricemia, Uric Acid、Pharmacological Effects of Natural Compounds、Inflammasome and immune disorders

Coptisine, one of the main active components of Rhizoma Coptidis, possesses anti-inflammatory, antioxidant, anti-apoptosis and renoprotective effects. In this study, we investigated the protective effect of coptisine against hyperuricemia induced renal injury in vitro and in vivo, and determined the underlying mechanism. In the in vivo experiment, a mouse model of hyperuricemia induced acute renal injury was established using potassium oxonate (PO)/ hypoxanthine (HX), and in the in vitro experiment, HK-2 cells injury was induced by uric acid (UA). Results showed that coptisine treatment significantly attenuated the acute renal injury via reducing kidney weight and coefficient, UA, creatinine (CRE), blood urea nitrogen (BUN), and histological damages. Meanwhile, coptisine treatment significantly suppressed hyperuricemia induced oxidant stress, inflammatory injury and apoptosis through promoting superoxide dismutase (SOD) activity, restraining reactive oxygen species (ROS), malondialdehyde (MDA), tumor necrosis factor (TNF)-α, interleukin (IL)- 1β, IL-18 levels, down-regulating protein expressions of cleaved-caspase 3, apoptosis-inducing factor (AIF), cyto-CytC, cleaved poly ADP-ribose polymerase (PARP) and Bcl-2-associated X protein (Bax), and up-regulating protein expressions of Bcl-2 and p-Bad. Additionally, mitochondrial structure damage and ATP depletion in renal tissue and HK-2 cells were observably alleviated. Of note, coptisine treatment remarkably ameliorated hyperuric...