ponicidin and Diabetic-Nephropathies

Cognitive impairment is a major complication of diabetes mellitus, which is caused by constitutive hyperglycaemia. Ponicidin is a diterpenoid isolated from a Chinese traditional herb (Rabdosia rubescens) and demonstrates the various pharmacological effects. The goal of this study was to scrutinise the neuroprotective effect of ponicidin against diabetic nephropathy (DN) induced by streptozotocin (STZ). Intraperitoneal administration of STZ (55 mg/kg) was used for the induction of diabetes and rats were received oral administration of ponicidin (5, 10 and 15 mg/kg) until 28 days. The body weight, food intake, water intake and blood glucose level were assessed at regular time interval. Plasma insulin level, antioxidant, inflammatory cytokines, apoptosis marker and faecal gut microbiota compositions were estimated. DN-induced group rats revealed the augmented glucose level, water intake, food intake and reduced body weight. Ponicidin significantly (P < 0.001) repressed the glucose level and water food intake and improved the body weight and plasma insulin. Ponicidin significantly (P < 0.001) repressed the malonaldehyde (MDA) level and boosted the level of glutathione (GSH), glutathione reductase (GR) and superoxide dismutase (SOD) in the brain and serum level. Ponicidin significantly (P < 0.001) repressed the level of interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and enhanced the level of interleukin-4 (IL-4), interleukin-10 (IL-10) in the brain and serum level. DN group rats exhibited the enhanced relative abundance of Firmicutes, along with enhancing the Firmicutes/Bacteroidetes ratio and repressing the Bacteroidetes relative abundance. Ponicidin effectually restored the relative abundance of Allobaculum, Lactobacillus and Ruminococcus genera. Our findings clearly demonstrated that ponicidin has a neuroprotective effect against diabetic cognitive impairment through modulating the gut microbiome.

Topics: Animals; Body Weight; Diabetes Mellitus; Diabetic Nephropathies; Diterpenes; Gastrointestinal Microbiome; Glucose; Glutathione; Insulins; Interleukin-6; Neuroprotective Agents; Oxidative Stress; Rats

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-α), interleukin-1β (IL-1β), nuclear factor-kappa B (NF-κB), 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.

Topics: Animals; Antioxidants; Biomarkers; Body Weight; Diabetes Mellitus; Diabetic Nephropathies; Diterpenes; Female; Humans; Hyperlipidemias; Inflammation; Insulin Resistance; Kidney; Male; Oxidative Stress; Rats; Rats, Wistar; Reactive Oxygen Species; Streptozocin