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

Abstract

Background: 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.

Purpose: The objective of this work was to investigate the potential roles of salidroside against diabetic nephropathy and the underlying molecular mechanisms.

Methods: 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.

Results: 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.

Conclusions: Our data showed that salidroside plays a beneficial role against diabetic nephropathy in mice, which probably via Sirt1/PGC-1α mediated mitochondrial biogenesis.

Keywords: AMP activated protein kinase; AMPK; ANOVA; BUN; CON; DN; Diabetic nephropathy; Met; Mitochondrial biogenesis; PAS; PGC-1α; PVDF; Periodic Acid-Schiff stain; SAL; SEM; SMA; STZ; Salidroside; Sirt1; TBST; TEM; analysis of variance; blood urea nitrogen; control; diabetic nephropathy; metformin; peroxisome proliferator-activated receptor gamma coactivator 1-alpha; polyvinylidene difluoride; salidroside; smooth muscle actin; standard error of the mean; streptozocin; transmission electron microscope; tris-buffered saline solution/Tween.