Effects of puerarin in STZ-induced diabetic rats by oxidative stress and the TGF-β1/Smad2 pathway

Abstract

The present study aimed to investigate the effects of pueraria on streptozotocine (STZ)-induced renal damage and its possible mechanisms. Wistar rats were randomly divided into five groups: the normal control group, diabetes untreated model group, two dosages (140 and 200 mg per kg bw per day) of puerarin treatment groups and a positive control group. Rats were studied 30 days after the STZ treatment, and the diabetes untreated model group presented significantly higher kidney index, blood glucose, triglyceride (TG), total cholesterol (TC), malondialdehyde (MDA), interferon-γ (IFN-γ), and IFN-γ/IL-4 levels, lower body weight, fasting blood insulin (FPI), IL-4, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and nitric oxide (NO) levels and worse renal function (higher blood urea nitrogen (BUN), serum creatinine (SCr), urine protein (UP) levels and glomerular extracellular matrix (relative area)) compared with the normal control group (p < 0.05). Furthermore, RT-FQ-PCR and western blot analyses showed that TGF-β1, Smad2, CTGF and FN protein and mRNA expression was significantly increased in the diabetes untreated model group compared with the normal control group. In contrast, the puerarin treatment dose-dependently significantly decreased the kidney index, blood glucose, TG, TC, MDA, IFN-γ, and IFN-γ/IL-4 levels, increased the body weight, FPI, IL-4, SOD, CAT, GSH-Px and NO levels and improved the renal function (lower BUN, SCr, UP levels and glomerular extracellular matrix (relative area)) in puerarin treatment groups (p < 0.05). In addition, the mRNA and protein expression of TGF-β1, Smad2, CTGF and FN was downregulated. It can be concluded that puerarin exerted its anti-diabetic effect on the STZ-treated rats through the inhibition of the TGF-β1/Smad2 pathway.