Modulatory role of blackberry fruit standardized extract on brain redox status and insulin signaling in type 2 diabetic rats

BACKGROUND: This study explored the effect of blackberry fruit extract (BFE) and metformin (Met) on biochemical markers, redox parameters, and the downstream insulin signaling pathway in a high-fat diet (HFD) + streptozotocin (STZ) induced Type 2 Diabetic Rat model. METHODS: The identification and quantification of cyanidin-3-glucoside by HPLC in the BFE revealed a concentration of 28.33 ± 0.05 mg/g of dry extract. For in vivo study, Type 2 Diabetes Mellitus (T2DM) was induced in rats by feeding a HFD for 3 weeks, followed by a single intraperitoneal dose of STZ on day 21. Animals were divided into 4 groups: I – Control, II – T2DM, III – T2DM plus Met (250 mg/kg) and IV – T2DM plus BFE (200 mg/kg). After STZ administration, the animals underwent a glucose tolerance test. Biochemical and molecular analyses were performed in serum and brain tissues. RESULTS: BFE and Met improved diabetic parameters, mitigating hyperglycemia, dyslipidemia, and inflammation by lowering serum glucose, total cholesterol, triglycerides, very low-density lipoprotein, interleukin-6, adenosine deaminase activity, and reactive species levels, while restoring high-density lipoprotein and paraoxonase-1 activity in blood. Both treatments reduced oxidative stress in the cerebral cortex by lowering reactive species, nitrite, and thiobarbituric acid reactive substances levels and increasing sulfhydryl groups, superoxide dismutase and catalase activity. Also, BFE upregulated phosphatidylinositol 3-kinase, insulin receptor substrate-1, forkhead box O-3a in the cerebral cortex. CONCLUSION: These findings highlight the potential of BFE as a promising natural therapeutic agent for T2DM management, demonstrating efficacy comparable to Met in addressing metabolic and oxidative impairments.