Ponicidin attenuates streptozotocin-induced diabetic nephropathy in rats via modulating hyperlipidemia, oxidative stress, and inflammatory markers

The present research work was proposed to discover the beneficial roles of ponicidin against the streptozotocin (STZ)-induced diabetic nephropathy (DN) in rats via modulating the oxidative stress and inflammation. The DN was initiated to the Wistar rats via administering 45 mg/kg of STZ and then diabetic animals were supplemented with 50 mg/kg of ponicidin and 150 mg/kg of metformin (standard drug) for 8 weeks. The body weight and food intake of animals were checked every week. The glucose, insulin, and homeostasis model assessment- insulin resistance (HOMA-IR) levels in the serum were assessed using kits. The levels of reactive oxygen species (ROS) accumulation, oxidative stress and antioxidant markers, and pro-inflammatory cytokines were examined using assay kits. The levels of lipid profiles and renal function markers were investigated using respective kits. The renal tissues were analyzed microscopically to detect the histological alterations. The ponicidin treatment effectively decreased the body weight, food intake, HOMA-IR, and HbAlc levels in the DN animals. The levels of ROS and MDA were decreased and superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR) activities were improved by the ponicidin. The ponicidin also reduced the blood urea nitrogen (BUN), creatinine, lactate dehydrogenase (LDH), and kidney injury molecule (KIM-1) levels. The levels of low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL), free fatty acid (FFA), and total cholesterol (TC) were decreased and the high-density lipoprotein (HDL) level was improved by the ponicidin treatment to the DN rats. The tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), nuclear factor-kappa B (NF-kappa B), and IL-6 levels were appreciably attenuated by the ponicidin. The ponicidin also ameliorated the DM-provoked histological alterations in the renal tissues. In conclusion, this study work evidenced that ponicidin has the therapeutic action in ameliorating the development of DN via averting oxidative stress, inflammation, and renal injury. It could be a promising therapeutic agent to treat DN in the future.