Astragaloside IV ameliorates diabetic nephropathy by modulating the mitochondrial quality control network.

Abstract

The aim of this study was to investigate the effect and possible mechanism of Astragaloside IV (AS-IV) on retarding the progression of diabetic nephropathy (DN) in a type 2 diabetic animal model, db/db mice. Eight-week-old male db/db diabetic mice and their nondiabetic littermate control db/m mice were used in the present study. AS-IV was administered to the db/db mice by adding it to standard feed at a dose of 1g/kg for 12 weeks. Renal injury was assessed by urinary albumin excretion (UAE) and Periodic acid-Schiff staining. The protein expression levels of mitochondrial quality-control-associated proteins were evaluated using Western blotting and immunohistochemical staining analysis. At the end of the experiment, db/db mice showed overt renal injury, as evidenced by increased UAE, increased urinary N-acetyl-β-D-glucosaminidase (NAG), expansion of mesangial matrix, and increased renal tubular area. AS-IV administration significantly reduced UAE and urinary NAG and ameliorated the renal pathologic injury seen in db/db mice. Furthermore, the expression of dynamin-related protein 1 (Drp-1), mitochondrial fission protein 1 (Fis-1), and mitochondrial fission factor (MFF), the main regulators of mitochondrial fission, was significantly increased in db/db mice. Moreover, PTEN-induced putative kinase 1 (PINK1)/Parkin-mediated mitophagy was abnormally activated in db/db mice. AS-IV significantly reduced renal Drp-1, Fis-1, and MFF expression and downregulated PINK1/Parkin-mediated mitophagy in db/db mice. However, mitochondrial biogenesis and mitochondrial fusion-associated protein levels were not significantly different between db/m and db/db mice in our study, with or without AS-IV treatment. In conclusion, administration of AS-IV could retard DN progression in type 2 diabetes mice, which might be associated with restoration of the mitochondrial quality control network.

• Authors: Xinhui Liu, Wenjing Wang, Gaofeng Song, Xian Wei, Youjia Zeng, Pengxun Han, Dongtao Wang, Mumin Shao, Juan Wu, Huili Sun, Guoliang Xiong, Shunmin Li
• Journal: PloS one (PLoS One) Vol. 12 Issue 8 Pg. e0182558 ( 2017) ISSN: 1932-6203 [Electronic] United States
• PMID: 28767702 (Publication Type: Journal Article)

Chemical References

• Albumins
• Saponins
• Triterpenes
• astragaloside A

Topics

• Albumins (analysis)
• Albuminuria (urine)
• Animals
• Diabetes Mellitus, Experimental (complications, metabolism)
• Diabetic Nephropathies (drug therapy, metabolism)
• Gene Expression Regulation (drug effects)
• Gene Regulatory Networks (drug effects)
• Male
• Mice
• Mitochondria (drug effects, metabolism)
• Mitochondrial Dynamics (drug effects)
• Saponins (administration & dosage, pharmacology)
• Triterpenes (administration & dosage, pharmacology)