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

• Published in: Biomedicine & pharmacotherapy Vol. 156; p. 113941
• Main Authors: Liu, Yanlu, Gong, Shiting, Li, Kejian, Wu, Gong, Zheng, Xiaohong, Zheng, Jingna, Lu, Xiaowei, Zhang, Luyao, Li, Jincan, Su, Ziren, Liu, Yuhong, Xie, Jianhui, Chen, Jiannan, Li, Yucui
• Format: Journal Article
• Language: English
• Published: Elsevier Masson SAS 01.12.2022; Elsevier
• Subjects: Coptisine; Hyperuricemic nephropathy; Inflammation; Mitochondrial apoptosis; Oxidative stress; PI3K/Akt signaling pathway; Oxidative stress; HN; SOD; Hyperuricemic nephropathy; PARP; Inflammation; MDA; UA; HX; Coptisine; PI3K; TNF-α; CRE; ROS; Bax; BUN; Mitochondrial apoptosis; PI3K/Akt signaling pathway; AIF; PO
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2022.113941

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 hyperuricemia induced phosphatidylinositol 3-kinase (PI3K)/ protein kinase B (PKB/Akt) signaling pathway inhibition. When interference with Akt, the protective effect of coptisine against UA-induced injury in HK2 cells was reversed. All the results suggested that coptisine could protect against hyperuricemia induced renal inflammatory damage, oxidative stress and mitochondrial apoptosis via regulating PI3K/Akt signaling pathway. [Display omitted] •Coptisine reduced the level of uric acid and ameliorated hyperuricemia-induced renal injury.•Coptisine attenuated renal inflammatory injury, oxidative stress and mitochondrial apoptosis in Hyperuricemic nephropathy.•The PI3K/Akt signaling pathway mediated the protective effects of coptisine against hyperuricemia-induced renal injury.