Compare Phellodendri Chinensis Cortex before and after salt-water processing to ameliorate diabetic nephropathy via metabolomics and microbiome analysis

OBJECTIVES: The study aims to investigate the therapeutic effects and the underlying mechanisms of Phellodendri Chinensis Cortex (PC) and its salt-water processed form (SPC) on diabetic nephropathy (DN). METHODS: Histopathological examination, biochemical evaluation immunohistochemistry/immunofluorescence assay were used to compare the effects of PC and SPC on DN. Intestinal microbiota was sequenced by 16S rDNA, serum differential metabolites were identified by UPLC-Q/TOF-MS to elucidate the mechanism. RESULTS: PC and SPC could improve renal function, reduce blood glucose, proteinuria, inflammation, and oxidative stress, and restoring gut microbiota homeostasis in DN rats, with SPC showing superior efficacy. PC influenced 8 metabolites, primarily in glycerolipid metabolism and pentose and glucuronate interconversions, whereas SPC affected 30 metabolites, predominantly in pathways closely associated with glucose and lipid metabolism, including pentose and glucuronate interconversions, ether lipid metabolism and glycerophospholipid metabolism. Correlation analysis identified specific gut microbiota, such as Enterobacteriaceae, Muribaculaceae, and Lachnospiraceae, as highly correlated with the metabolic effects induced by PC and SPC. CONCLUSION: The study provides evidence that PC and SPC have a beneficial effect on DN, with SPC exhibiting enhanced therapeutic potential. Furthermore, SPC could better restore gut microbiota diversity and structure, and improved glucose and lipid metabolism.