Diosgenin protects against podocyte injury in early phase of diabetic nephropathy through regulating SIRT6

作者：Zhi Wang, Qiao Wu, Hongzhan Wang, Yang Gao, Kexin Nie, Yueheng Tang, Hao Su, Meilin Hu, Jing Gong, Ke Fang, Hui Dong · 发表于：Phytomedicine · 年份：2022 · DOI：10.1016/j.phymed.2022.154276 · 被引用次数：43 · 研究领域：Phytochemical Studies and Bioactivities、Natural Antidiabetic Agents Studies、Phytochemistry and Biological Activities

BACKGROUND: Diabetic nephropathy (DN) is a serious complication of diabetes mellitus. DN is the main cause of end-stage renal disease (ESRD). SIRT6 becomes the important target of DN. Diosgenin (a monomer from Chinese herbs) is probable to bind to SIRT6. PURPOSE: Based on studies presented in the literature on kidney injuries plus screening for the binding effects of the drug to Sirt6, we aimed to carry out the study to assess the effects of diosgenin involved in improving podocyte damage in the early phase of DN.. METHODS: DN model was established in spontaneous diabetic db/db mice. Animal experiment was in two parts. The first part includes four groups consisting of control (Con) group, model (Mod) group, low dose of diosgenin (DL) group and high dose of diosgenin (DH) group. The second part includes four groups consisting of control group, model group, DH+OSS_128167 (OSS, inhibitor of SIRT6) group, MDL800 (agonist of SIRT6) group. MPC5 cell line was selected in cell experiment, which was mainly composed of six groups including Con group, palmitic acid (PA) group, PA+DL group, PA+DH group, PA+DH+OSS group, PA+MDL800 group. Some procedures such as transcriptomics, RT-qPCR and so on were used in the study to explore and verify the mechanism. RESULTS: The abnormal changes of mesangial matrix expansion, glomerular basement membrane (GBM) thickness, foot process (FP) width, urine albumin/creatinine (UACR), DESMIN, ADRP, NEPHRIN, PODOCIN, SIRT6 in Mod group were alleviated in DH ...