Pakistan Journal of Pharmaceutical Sciences

Abstract: Background: DKD is a leading cause of end-stage renal disease with limited therapeutic options. Objectives: This study evaluated the effects of Xiaoshen Formula (XSF) on glucose/lipid metabolism and renal injury in a DKD model of mice and preliminarily explored its mechanisms involving the JAK/STAT pathway and PPAR?. Methods: Diabetes and early-stage DKD were established in KK-Ay mice. Successfully modeled mice were randomly assigned to preventive or therapeutic administration groups; C57BL/6J mice served as blank controls. Biochemical parameters, kidney index and renal histopathology (hematoxylin-eosin staining and transmission electron microscopy) were assessed. Renal protein expression was determined by Western blot. Results: Compared with blank controls, model mice exhibited increased body weight, polydipsia, polyphagia, disrupted glucose/lipid metabolism and renal injury, confirming successful modeling. Irbesartan reduced fasting blood glucose, kidney weight, organ index and renal injury. XSF-H significantly improved glucose/lipid metabolism, reduced food/water intake and kidney weight/organ index and alleviated renal injury, with overall efficacy ranking: high-dose > therapeutic > low-dose. Western blot showed lower levels of JAK2, p-STAT-6, TGF-?1, and FN, and higher levels of PPAR? in the Irbesartan and XSF groups compared with the model group. Conclusion: This study provides experimental evidence that XSF may delay early DKD progression. XSF ameliorates fasting blood glucose, stabilizes body weight, improves glucose/lipid metabolism and attenuates renal injury and no obvious hepatorenal toxicity under limited conditions. Findings suggest that XSF delays DKD progression may be associated with modulation of the JAK/STAT signaling pathway and inhibition of renal fibrosis.