Blackberry extract ameliorates metabolic and oxidative dysfunction in experimental diabetes

Type 2 diabetes mellitus (T2DM) is associated with metabolic dysfunction, oxidative stress, and impaired insulin signaling, highlighting the need for alternative therapeutic approaches. This study aimed to investigate the effects of blackberry fruit extract (BFE) and metformin (Met) on biochemical parameters, redox balance, and insulin signaling in a high-fat diet (HFD) and streptozotocin (STZ)-induced T2DM rat model. Cyanidin-3-glucoside (C3G) was identified and quantified in BFE using high-performance liquid chromatography (HPLC). T2DM was induced by feeding rats an HFD for three weeks, followed by a single intraperitoneal STZ injection on day 21. Animals were divided into four groups: Control, T2DM, T2DM + Met (250 mg/kg), and T2DM + BFE (200 mg/kg). Following STZ administration, a glucose tolerance test was performed, and biochemical and molecular analyses were conducted in serum and brain tissues. HPLC analysis revealed a C3G concentration of 28.33 ± 0.05 mg/g of dry extract. Both BFE and Met improved glycemic and lipid profiles, reducing serum glucose, total cholesterol, triglycerides, very-low-density lipoprotein, interleukin-6, adenosine deaminase activity, and reactive species levels, while increasing high-density lipoprotein and paraoxonase-1 activity. In the cerebral cortex, both treatments attenuated oxidative damage by reducing reactive species, nitrite, and thiobarbituric acid-reactive substances while enhancing sulfhydryl groups, superoxide dismutase, and catalase activity. Furthermore, BFE upregulated phosphatidylinositol 3-kinase, insulin receptor substrate-1, and forkhead box O3a expression, suggesting modulation of insulin-related signaling pathways. These findings indicate that BFE exerts beneficial metabolic, anti-inflammatory, and antioxidant effects, potentially associated with its C3G content and modulation of insulin signaling. Its effects were comparable to metformin across several evaluated parameters, supporting further investigation of BFE as a potential complementary approach for T2DM management.

Keywords: Blackberry, 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.