Punica granatum L. peel extract protects diabetic nephropathy by activating the Nrf-2/HO-1 pathway

Diabetes raises cardiovascular morbidity and mortality worldwide and causes retinopathy, neuropathy, and nephropathy. Punica granatum L. (Pomegranate) is a fruit that has been used for its medicinal properties in various cultures. This article aims to investigate the antioxidant, anti-inflammatory, anti-apoptotic activity of Punica granatum L. peel ethanol extract (PGE) and its efficacy on NF-κB and Nrf-2/HO-1 signaling pathways in kidney tissue of rats with streptozotocin-induced diabetes. Single dose STZ 60 mg/kg/i.p. rats were given to induce diabetes and blood glucose measurements were taken 7 days later. PGE 10 mg/kg/p.o. administered to the treatment groups for 20 days. Blood, kidney, and pancreas samples taken from anesthetized rats were analyzed biochemically and histopathologically. It was observed that STZ increased the levels of urea, uric acid and creatine in the blood, while PGE significantly decreased these parameters. The diabetic group had higher MDA and lower renal tissue GSH level, CAT, GPx, and SOD activity than the control group. STZ also enhanced inflammation, apoptosis, Bax, Caspase-3, and NF-κB expression, and decreased Bcl-2, HO-1, and Nrf-2 expression. Experimental results showed that PGE has the potential to alleviate the harmful effects on the kidney and pancreas by altering the mentioned parameters in diabetic rats.