Picralima nitida leaf extract ameliorates oxidative stress and modulates insulin signaling pathway in high fat-diet/STZ induced diabetic rats

Abstract

The aqueous leaf extract of Picralima nitida has been shown to produce antipyretic and anti-inflammatory effects in the management of several disease conditions, including diabetes. This study examined the ameliorative effect of aqueous seed extract of Picralima nitida on elevated liver enzymes, oxidative stress parameters, and impaired insulin pathway in high fat-fed streptozotocin-induced diabetic rats. Experimental rats (8 weeks old) were fed a control diet or a high-fat diet for 30 days, followed by a one-time intraperitoneal (i.p.) injection of streptozotocin (45 mg/kg). P. nitida (50, 100, and 150 mg/kg dose) and metformin (50 mg/kg dose) were administered orally to the rats for 21 days. The liver enzymes, antioxidant enzyme markers as well as certain metabolic genes implicated in the insulin signaling system, were also evaluated. When compared to the conventional antidiabetic drug metformin, P. nitida at 150 mg/kg causes a significant decrease in blood glucose and ameliorated liver damage in diabetic rats. Treatment with P. nitida at 150 mg/kg also showed a significant increase in the level of superoxide dismutase (SOD) and catalase (CAT) but a significant decrease in the level of malonaldehyde (MDA) in the diabetic rats. Furthermore, at all experimental doses assayed, P. nitida strongly raised the mRNA expression of Nrf2, PI3K, AKT, and mTOR, but dramatically downregulated the mRNA expression of Keap1 and PTEN. The study has thus far shown that P. nitida holds significant promise in mitigating liver damage, oxidative stress, and aberrations in insulin signaling pathway associated with high-fat diet streptozotocin-induced diabetes.