Exploring the mechanisms of torularhodin in alleviating diabetic kidney disease: a microbiome and metabolomics approach through the gut-kidney axis

This study primarily investigates the pivotal role of torularhodin in alleviating diabetic nephropathy in mice. Oral administration of torularhodin at a dose of 30 mg/kg/day for 8 weeks significantly improved diabetic symptoms and mitigated kidney tissue damage in a mouse model of diabetic nephropathy. Integrating findings from both network pharmacology and in vivo experiments, the study confirmed that torularhodin activates the Nrf2 signaling pathway, thereby promoting the expression of multiple antioxidant enzymes to directly reduce oxidative stress and mitochondrial damage in renal tissues. Moreover, combined analyses of metabolomics and gut microbiota profiling revealed that torularhodin increased the abundance of Muribaculaceae , Moraxellaceae , and Erysipelotrichaceae , while decreasing the abundance of Lactobacillaceae and Enterobacteriaceae . These microbial shifts were accompanied by increased levels of key metabolites, such as Glycerol 3-Phosphate and d -Fructose 6-Phosphate, which helped alleviate amino acid metabolic disorders, restore energy metabolism, and reduce oxidative stress in the kidneys via the gut-kidney axis. This study demonstrates that the protective effects of torularhodin against diabetic nephropathy arise both from its direct antioxidant and mitochondrial protective actions, and partly from modulation of the gut microbiota and their metabolites. These findings provide new insights into the mechanisms of torularhodin and establish a theoretical basis for its potential use as a therapeutic strategy for diabetic nephropathy.