Celastrol slows the progression of early diabetic nephropathy in rats via the PI3K/AKT pathway

BMC Complementary Medicine and Therapies

Chengxiao Fu¹  Zhenyan Hou²  Xiaopei Tong³  Yao Li³  Huimin Zhang³  Miao Yan³  Yusong Nie⁴  Hui Xie⁵  Min Zhang⁶  Xinrong Fan⁷ 

[1] Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South University, 410013, Changsha, Hunan, China;Department of Pharmacy, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, 264000, Yantai, Shandong, China;Department of Pharmacy, The Second Xiangya Hospital, Central South University, 410011, Changsha, Hunan, China;Department of Pharmacy, The Second Xiangya Hospital, Central South University, 410011, Changsha, Hunan, China;Hunan University of Chinese Medicine, 410208, Changsha, Hunan, China;Xianyang Central Hospital, 712000, Xianyang, Shaanxi, China;Hunan University of Chinese Medicine, 410208, Changsha, Hunan, China;Hunan University of Chinese Medicine, 410208, Changsha, Hunan, China;First clinical medical college, Shaanxi University of Chinese Medicine, 712000, Xianyang, Shaanxi, China;Hunan University of Chinese Medicine, 410208, Changsha, Hunan, China;First clinical medical college, Shaanxi University of Chinese Medicine, 712000, Xianyang, Shaanxi, China;Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Sciences, 100700, Beijing, China;

关键词: Celastrol;    Diabetic nephropathy;    PI3K;    AKT;    Podocytes;    Autophagy;    Glomeruli basement membrane;   

DOI  :  10.1186/s12906-020-03050-y

来源: Springer

【 摘 要 】

BackgroundDiabetic nephropathy serves as one of the most regular microvascular complications of diabetes mellitus and is the main factor that causes end-stage renal disease and incident mortality. As the beneficial effect and minute adverse influence of Celastrol on the renal system requires further elucidation, the renoprotective function of Celastrol in early diabetic nephropathy was investigated.MethodsIn high-fat and high-glucose diet/streptozotocin-induced diabetic rats which is the early diabetic nephropathy model, ALT, AST, 24 h urinary protein, blood urea nitrogen, and serum creatinine content were observed. Periodic acid-Schiff staining, enzyme-linked immunosorbent assay, immunohistochemical analysis, reverse transcription-polymerase chain reaction, and western blot analysis were used to explore the renoprotective effect of Celastrol to diabetic nephropathy rats and the underlying mechanism.ResultsHigh dose of Celastrol (1.5 mg/kg/d) not only improved the kidney function of diabetic nephropathy (DN) rats, and decreased the blood glucose and 24 h urinary albumin, but also increased the expression of LC3II and nephrin, and downregulated the expression of PI3K, p-AKT, and the mRNA level of NF-κB and mTOR.ConclusionCelastrol functions as a potential therapeutic substance, acting via the PI3K/AKT pathway to attenuate renal injury, inhibit glomerular basement membrane thickening, and achieve podocyte homeostasis in diabetic nephropathy.

【 授权许可】

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