Tripterygium wilfordii mitigates hyperglycemia-induced upregulated Wnt/β-catenin expression and kidney injury in diabetic rats

Abstract

Aberrant activation of the Wnt/β-catenin pathway contributes to the development of diabetic nephropathy (DN); however, treatment with Tripterygium wilfordii (TW) may be beneficial for patients with DN. The aim of the present study was to evaluate the effect of TW on Wnt/β-catenin expression in the kidneys of diabetic rats. Male Sprague-Dawley rats were randomly injected with vehicle (control) or streptozotocin to induce diabetes. Diabetic rats were then randomly treated with vehicle (sodium carboxymethyl cellulose; SCC), TW combined with SCC (8 or 16 mg/kg) or irbesartan (50 mg/kg) daily for 8 weeks. Metabolic parameter levels and renal pathological changes were examined. mRNA and protein expression of Wnt-1, glycogen synthase kinase (GSK)-3β, β-catenin, nuclear factor (NF)-κB and transforming growth factor (TGF)-β1 in the kidneys of rats from all groups were measured. Compared with the DM group, metabolic parameters and morphological parameters, apart from blood glucose levels, were significantly improved in TW-treated rats (all P<0.01). Furthermore, levels of Wnt-1, β-catenin, NF-κB-p65 and TGF-β1 mRNA and protein were significantly reduced in the kidneys of TW-treated rats compared with DM rats, whereas levels of GSK-3β mRNA and protein did not differ significantly between any of the groups; however, the expression of P-GSK-3β protein was significantly decreased in the kidneys of TW-treated rats compared with the DM group. The protective effects of TW tended to be dose-dependent and were an improvement compared with irbesartan treatment in diabetic rats. Therefore, the results of the present study indicated that treatment with TW mitigated hyperglycemia-induced upregulated Wnt-1 and β-catenin expression in kidney tissues and ameliorated diabetes-induced kidney injury in rats.