Zhenqing recipe alleviates diabetic nephropathy in experimental type 2 diabetic rats through suppression of SREBP-1c.

ETHNOPHARMACOLOGICAL RELEVANCE: Zhenqing Recipe (ZQR), a Chinese herbal prescription, is used to improve renal function of patients with diabetic nephropathy. In current research, the therapeutic effects of ZQR on type 2 diabetic nephropathy and the underlying molecular mechanisms were explored.

MATERIALS AND METHODS: Animal model with diabetic nephropathy was developed by high fat/sucrose diet feeding plus streptozotocin injection for 4 weeks. The diabetic rats were then orally administered with ZQR extract at the dose of 4 g/kg, 8 g/kg body weight/day for 8 weeks.

RESULTS: Serum glucose, triglyceride and total cholesterol in untreated diabetic rats were significantly higher than that of normal control rats. ZQR treatment not only reduced serum glucose level in diabetic rats, but also decreased serum triglyceride and total cholesterol in a dose-dependent manner. Urinary albumin excretion rate, serum urea and creatinine were significantly decreased in ZQR groups compared with untreated diabetic group. Histopathological study of kidney samples showed that extracellular mesangial matrix expansion in diabetic rats was suppressed by ZQR treatment. Both mRNA and protein levels of sterol regulatory element binding-protein-1c (SREBP-1c), and its target genes including acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) in renal cortex were significantly decreased in ZQR treated rats compared to untreated diabetic rats. Consequently, renal triglyceride was significantly reduced in ZQR groups. Furthermore, ZQR significantly inhibited the overexpression of transforming growth factor-β1 and fibronectin in the renal cortex of diabetic rats.

CONCLUSIONS: Oral treatment of ZQR improved diabetic nephropathy by inhibiting the overexpression of SREBP-1c and its target genes including ACC and FAS in experimental type 2 diabetic rats.