Acacia nilotica leaf improves insulin resistance and hyperglycemia associated acute hepatic injury and nephrotoxicity by improving systemic antioxidant status in diabetic mice

Abstract

Ethnopharmacological relevanceAcacia nilotica (L.) Delile is used as a traditional anti-diabetic remedy in Bangladesh, Pakistan, Egypt, Nigeria and is mentioned in Ayurveda as well. AimThe objective of the study was to evaluate the ethnomedicinal claim of A. nilotica leaf (ANL) extract for its efficiency in ameliorating diabetic complications. Materials and methodsANL was orally administrated (50 and 200mg/kg) to alloxanized mice (blood glucose > 200mg/dL) for 20d. Parameters of glucose metabolism, hepatotoxicity, hyperlipidemia and nephrotoxicity were measured with emphasis on elevated oxidative stress. ANL was chemically characterized using GC-MS. Further, docking studies were employed to predict molecular interactions. ResultsANL lowered (65%, P< 0.001) systemic glucose load in diabetic mice, which was otherwise 398% higher than control. ANL lowered (35%) insulin resistance, without any significant effect on insulin sensitivity (P> 0.05). Anti-hyperglycemic properties of ANL was further supported by lowering of HbA1c (34%; P< 0.001) and improved glucose utilization (OGTT). Overall diabetic complications were mitigated as reflected by lowered hepatic (ALT, AST) and renal (creatinine, BUN) injury markers and normalization of dyslipidemia. Elevated systemic oxidative stress was lowered by increased catalase and peroxidase activities in liver, kidney and skeletal muscle, resulting in 32% decrease of serum MDA levels. Apart from high phenolic and flavonoid content, tocopherol, catechol and β-sitosterol, identified in ANL, demonstrated substantial binding affinity with Nrf2 protein (5FNQ) reflecting possible crosstalk with intracellular antioxidant defense pathways. ConclusionThe present study revealed the potentials of A. nilotica to alleviate diabetes-related systemic complications by limiting oxidative stress which justified the ethnopharmacological antidiabetic claim.