Anthocyanin-rich Eugenia uniflora attenuates metabolic dysfunction in experimental diabetes

Type 2 diabetes mellitus (T2DM) is associated with metabolic disturbances, oxidative stress, inflammation, and impaired insulin signaling, which may contribute to neurological complications. Eugenia uniflora is a fruit rich in bioactive compounds with potential metabolic and antioxidant properties. This study aimed to evaluate the in-vivo antidiabetic effects of a standardized E. uniflora fruit extract in comparison with metformin in a rat model of T2DM.

The cytotoxicity of the standardized E. uniflora extract was initially evaluated using the MTT assay. For the in-vivo study, male Wistar rats were divided into four groups: control, T2DM, T2DM treated with metformin (Met), and T2DM treated with E. uniflora extract. T2DM was induced by feeding animals a high-fat diet for three weeks followed by a single intraperitoneal injection of streptozotocin (35 mg/kg). Metformin (250 mg/kg) and E. uniflora extract (200 mg/kg) were administered intragastrically once daily throughout the experimental period. Serum metabolic and inflammatory parameters were assessed, while oxidative stress, antioxidant defense, and insulin-signaling-related markers were evaluated in the cerebral cortex, hippocampus, and striatum.

E. uniflora extract showed no significant cytotoxicity at the tested concentrations. In T2DM rats, treatment with either E. uniflora or metformin attenuated diabetes-associated alterations in serum glucose, cholesterol, LDL, triglycerides, and interleukin-6 levels. Both treatments also reduced oxidative stress and improved antioxidant enzyme activity in brain regions affected by metabolic dysfunction. Importantly, E. uniflora treatment improved components of the insulin signaling pathway, including insulin receptor substrate 1 (IRS1), phosphatidylinositol 3-kinase (PI3K), glycogen synthase kinase 3-β (GSK3β), and forkhead box O3a (FOXO3a), and enhanced nuclear factor erythroid 2-related factor 2 (NRF2) activation in the cerebral cortex. These findings indicate that the beneficial effects of the extract may involve the combined modulation of metabolic, inflammatory, oxidative, and insulin-signaling pathways.

Standardized E. uniflora fruit extract demonstrated beneficial metabolic, antioxidant, and insulin-signaling effects in experimental T2DM, with responses comparable in several parameters to metformin. The findings support further investigation of E. uniflora as a potential complementary approach for mitigating metabolic and neurological complications associated with T2DM.

Keywords: Eugenia uniflora, Anthocyanins, Type 2 diabetes, oxidative stress, Insulin signaling

Acknowledgments: The authors gratefully acknowledge the Coordination for the Improvement of Higher Education Personnel (CAPES), Brazil, for the financial support provided for this study.