Xiaoshen formula delays progression of diabetic kidney disease and improves glucose and lipid metabolism: Association with the JAK/STAT pathway.

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 PPARγ.

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-β1, and FN, and higher levels of PPARγ 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.