Protective Effect of Pueraria lobate (Willd.) Ohwi root extract on Diabetic Nephropathy via metabolomics study and mitochondrial homeostasis-involved pathways

[Display omitted] •RP extract can regulate mitochondrial biogenesis and autophagy in DN mice.•Protective mechanism of RP on DN was explored by metabolomics and molecular biology.•32 potential biomarkers were collected using UPLC-Q-TOF/MS.•AMPK/SIRT1/PGC-1α and PINK1/Parkin pathway are involved in the effect of RP on DN. Radix Puerariae (RP) is a kind of medical and edible material and is used to treat diabetes and diabetic nephropathy (DN). However, the protective effect of RP against DN has not been explained clearly. A DN mice model was established through the co-treatment of cadmium and high fat and sugar diet (HFSD), different doses of RP extracts were given. Biochemical parameters and histopathological observation were performed to confirm the protective effect of RP on DN mice. Moreover, metabolomics analysis and molecular verification were carried out to explore the mechanism of RP extracts on DN. The results showed that RP extracts has a good hypoglycemic effect and renal- protective effect on DN mice. RP could restore the dynamic balance of mitochondrial biosynthesis and autophagy through the regulation of AMPK/SIRT1/PGC-1α and PINK1/Parkin signaling pathway, which may provide new insight for the application of RP as functional food in the prevention of DN.