Yishen Xiaoke Formula Delays Renal Fibrosis in Rats with Diabetic Nephropathy by Suppressing the Transforming Growth Factor-Beta 1/Notch Signalling Pathway.

BACKGROUND

Yishen Xiaoke Formula (YSXKF), derived from the classical prescription Yuquan San, has been used clinically to treat diabetic nephropathy (DN) in patients with qi-yin deficiency syndrome.

OBJECTIVES

This study investigated whether YSXKF delays renal fibrosis progression in DN rats by regulating the transforming growth factor-beta 1 (TGF-β1)/Notch signalling pathway.

METHODS

Seventy-five male Sprague Dawley rats were included and randomly assigned to a control cohort (15 rats) or a model cohort (60 rats). DN was induced by unilateral nephrectomy, a high-fat/high-sucrose diet, and streptozotocin injection. DN rats were treated with YSXKF, irbesartan, or YSXKF combined with TGF-β1 activation for 8 weeks. After 8 weeks of intervention, 24-h urinary total protein (24-h UTP), circulating TGF-β1 levels, fasting blood glucose (FBG), and serum creatinine (Scr) were evaluated. Masson staining was performed to assess renal pathological changes, and quantitative reverse transcription polymerase chain reaction and immunohistochemistry were conducted to assess the levels of TGF-β1, Jagged1, and Hes1 in renal tissue.

RESULTS

Compared with DN rats, YSXKF treatment significantly reduced 24-h UTP excretion, circulating TGF-β1 levels, FBG, and Scr. Histological analysis revealed attenuated glomerulosclerosis and interstitial fibrosis. YSXKF decreased renal mRNA and protein expression of TGF-β1, Jagged1, and Hes1. Activation of TGF-β1 markedly reversed these protective effects and restored Notch pathway activation.

CONCLUSIONS

YSXKF delays renal fibrosis progression in DN rats by downregulating TGF-β1 expression and inhibiting Jagged1/Hes1 activation in the Notch signaling pathway, thereby reducing extracellular matrix deposition.