Anti-Hyperlipidemic, Antioxidant, Anti-Inflammatory and Antidiabetic Effect of Brucine Against Streptozotocin-Induced Diabetic Nephropathy in Rats

Abstract

Among the diabetes-related complications, diabetic nephropathy is the major complication and it leads to end-stage renal failure. In the current investigation, we examined the protection of brucine, an alkaloid extracted from the seeds of Strychnos nux vomica plant widely used in traditional Chinese and Indian medicines against diabetic-induced nephropathy. Male Wistar rats were divided into four groups: control, diabetic rats, diabetic-induced + 40 mg/kg brucine-treated rats, and diabetic-induced + 25 mg/kg metformin-treated rats. The 35 mg/kg streptozotocin (STZ) was injected into (i.p.) rats to induce diabetes, and then rats were post-treated with brucine and metformin for 45 days. The food intake, weight gain, fasting blood glucose, HbA1C, insulin, and HOMA-IR values were measured on initial and after completion of treatment to confirm the induction of diabetes by STZ and the antidiabetic effect of brucine. The rats were euthanized on 45th day, and kidney tissue was isolated to assess the nephroprotective effect of brucine. The antioxidant property of brucine was analyzed by measuring the oxidative stress and antioxidant biomarkers. The lipid profiles in the control and treated rats were measured. To assess the nephroprotective effect of brucine KIM-1 protein was measured. The anti-inflammatory property of brucine was assessed by quantifying the levels of pro-inflammatory cytokines i.e., NF-κB, TNF-α, IL-1β, IL-6, TGF-β and to confirm the nephroprotective effect. The histopathological analysis was also performed with H&E staining. Our results suggested that brucine showed potent antidiabetic, antioxidant, antilipidemic, anti-inflammatory, and nephroprotective properties.