Nrf2 activator corosolic acid meliorates alloxan induced diabetic nephropathy in mice

Abstract

Objective: To determine whether corosolic acid (CA) targeting nuclear protein expression of Nrf2 activation can be used to attenuate renal damage and preserve renal function in alloxan diabetic mice. Methods: A mouse model with diabetic nephropathy was established to examine the Nrf2 expression. Mice were randomly divided into control, diabetic control, and CA groups treated at 0.4 mg/kg, 2 mg/kg and 10 mg/kg p.o. for 8 weeks. Diabetes was induced in mice by single intraperitoneal injection of alloxan 200 mg/kg in all groups except the control. The mice with fasting blood glucose level over 200 mg/dL were considered as diabetic and were employed in the study. After 4th and 8th weeks, urine samples were collected (using metabolic cages) to measure protein and urea. Animals were euthanized, and serum samples were collected to estimate the glucose, creatinine, total protein, urea and blood urea nitrogen. Kidney was isolated at the end of experiment for histology to evaluate anti-oxidant parameters. Immunohistochemistry was performed to examine the Nrf2 expression. Results: CA treatment showed dose dependent reduction in level of biochemical parameters in serum and urine. CA group (10 mg/kg) showed significantly higher body weight and reduced kidney weight. Histopathological examination revealed reduced inflammation, collagen deposition and glomerulosclerosis in renal tissue. CA attenuated renal dysfunction, oxidative stress and inflammatory pro-cytokine levels. Conclusions: CA treatment exhibited ameliorative effect on kidney in mice with its enhanced Nrf2 expression.

Keywords

• Corosolic acid
• Nrf2
• Diabetic nephropathy
• Oxidative stress
• Inflammation
• Pentacyclic triterpenoid