Zingerone produces antidiabetic effects and attenuates diabetic nephropathy by reducing oxidative stress and overexpression of NF-κB, TNF-α, and COX-2 proteins in rats
Brahmjot Singh, Brahmjot Singh, Ajay Kumar, H.B. Singh, Sarabjit Kaur, Satwinderjeet Kaur, Harpal S. Buttar, Saroj Arora, Balbir Singh, Balbir Singh
Abstract
Diabetes mellitus (DM) is characterized by impaired insulin secretion or utilization, accompanied by hyperglycemia and glycosuria, as well as by a plethora of DM-induced complications, including nephropathy. The purpose of this investigation was 2-fold: to evaluate the antidiabetic potential of zingerone, and its protective effects against DM-induced nephropathy. It has been reported that oxidative stress is associated with DM and cellular nuclear factor (NF)-κB, tumour necrosis factor (TNF)-α and cyclooxygenase (COX)-2 proteins are overexpressed in DM-triggered nephropathy. The levels of these molecular biomarkers and renal functions were measured in zingerone treated diabetic animals. DM was produced in adult male Wistar rats with streptozotocin/nicotinamide. Zingerone (15, 30 and 60 mg/kg) was administered orally once daily to diabetic rats for 6 consecutive weeks. Significant increase in serum glucose, total cholesterol, low density lipoproteins (LDL), urea, uric acid, creatinine, glutamic oxaloacetic transaminase (SGOT), glutamic pyruvic transaminase (SGPT) and alkaline phosphatase (ALP) was observed in diabetic rats. All these biochemical parameters were significantly reduced in zingerone treated animals in a dose-dependent manner. There was a marked increase in renal levels of thio-barbituric acid reactive substance (TBARS), superoxide anion generation (SAG) and decrease in reduced glutathione (GSH) in diabetic rats. Whereas zingerone treatment showed statistically significant attenuation of all the oxidative stress parameters, in comparison with untreated counterparts. The overexpressed levels of NF-κB, TNF-α and COX-2 proteins in nephropathic rats were attenuated by zingerone. Histological examination of isolated kidneys confirmed the renoprotective effects of zingerone. Our results suggest that the antidiabetic and renoprotective effects of zingerone seem to be due to the combination of different actions: namely antioxidant and anti-inflammatory properties, inhibition of DM-induced oxidative stress by scavenging free radicals, and down-regulation of NF-κB, TNF-α and COX-2 proteins in the kidney tissue.