Salidroside stimulates the Sirt1/PGC-1α axis and ameliorates diabetic nephropathy in mice

• Published in: Phytomedicine (Stuttgart) Vol. 54; pp. 240 - 247
• Main Authors: Xue, Haiyan, Li, Peipei, Luo, Yishu, Wu, Chuwen, Liu, Yue, Qin, Xiaogang, Huang, Xinzhong, Sun, Cheng
• Format: Journal Article
• Language: English
• Published: Germany Elsevier GmbH 15.02.2019
• Subjects: AMP activated protein kinase; AMPK; analysis of variance; Animals; ANOVA; blood urea nitrogen; BUN; CON; control; Diabetic Nephropathies - metabolism; Diabetic Nephropathies - prevention & control; Diabetic nephropathy; Disease Models, Animal; DNA, Mitochondrial - metabolism; Electron Transport; Glucosides - pharmacology; Male; Met; metformin; Mice; Mice, Inbred C57BL; Mice, Obese; Mitochondria - metabolism; Mitochondrial biogenesis; PAS; Periodic Acid-Schiff stain; peroxisome proliferator-activated receptor gamma coactivator 1-alpha; PGC-1α; Phenols - pharmacology; Podocytes - metabolism; polyvinylidene difluoride; PVDF; SAL; Salidroside; SEM; Sirt1; Sirtuin 1 - drug effects; Sirtuin 1 - metabolism; SMA; smooth muscle actin; standard error of the mean; Streptozocin; STZ; TBST; TEM; Transcription Factors - drug effects; Transcription Factors - metabolism; transmission electron microscope; tris-buffered saline solution/Tween; Up-Regulation; PAS; CON; SMA; TBST; PGC-1α; DN; PVDF; Salidroside; Mitochondrial biogenesis; ANOVA; STZ; Diabetic nephropathy; AMPK; Sirt1; SEM; BUN; TEM; Met; SAL; blood urea nitrogen; analysis of variance; Periodic Acid-Schiff stain; polyvinylidene difluoride; metformin; control; AMP activated protein kinase; transmission electron microscope; peroxisome proliferator-activated receptor gamma coactivator 1-alpha; streptozocin; standard error of the mean; smooth muscle actin; tris-buffered saline solution/Tween
• ISSN: 0944-7113; 1618-095X
• DOI: 10.1016/j.phymed.2018.10.031

Salidroside, an active component from Traditional Chinese Medicine Rhodiola rosea L., has various pharmacological functions including anti-inflammatory, anti-cancer and anti-oxidative properties. However, whether salidroside plays a beneficial role in diabetic nephropathy is still unclear. The objective of this work was to investigate the potential roles of salidroside against diabetic nephropathy and the underlying molecular mechanisms. Streptozocin was given to obese mice to generate diabetic nephropathy animal model. Salidroside was administered to these mice and proteinuria, podocyte integrity, renal morphology and fibrosis, mitochondrial biogenesis were examined. Our results showed that salidroside treatment greatly attenuates diabetic nephropathy as evidenced by decreased urinary albumin, blood urea nitrogen and serum creatinine. Morphological analysis indicated that salidroside improves renal structures in diabetic nephropathy. The decreases in nephrin and podocin expression were markedly reversed by salidroside. Moreover, kidney fibrosis in diabetic nephropathy mice was largely prevented by salidroside. Mechanistically, in salidroside-treated mice, the mitochondrial DNA copy and electron transport chain proteins were significantly enhanced. Meanwhile, the reduced Sirt1 and PGC-1α expression in diabetic nephropathy was almost completely counteracted in the presence of salidroside. Our data showed that salidroside plays a beneficial role against diabetic nephropathy in mice, which probably via Sirt1/PGC-1α mediated mitochondrial biogenesis. [Display omitted]