Sen_2026_Ibrain_12_259

Flavone derivatives of natural products are often synthesized to enhance their structural specificity, target selectivity, and bioavailability. The current study aimed to examine the neuroprotective efficacy of flavone derivative in diabetic associated neurodegenerations through systematic assessments of in-silico and in-vivo. The synthesized flavone (2-phenyl-4H-chromen-4-one) was characterized by NMR spectroscopy and FTIR. The in-vivo assessments were performed by following the serum biochemistry of homeostatic model assessment (HOMA), antioxidant and histopathology of cortex and hippocampus. The in-silico assessment of molecular docking showed -6.6 Kcal/mol with dipeptidyl peptidase-4 enzyme (DPP4), -7.8 with acetylcholinesterase (AChE), and -9.5 with butyrylcholinesterase (BuChE). The diabetic neurodegeneration model was induced by the chemical induction method and treated with the test compound at a dose of 40 mg/kg in comparison to sitagliptin. The treatment of the test compound showed significant alterations in the cortex and hippocampus region with mitigated neuronal injuries which endorsed by expressions targeted genes including glucose transporter 3 (GLUT-3), glycogen synthase kinase 3 beta (GSK-3beta), microtubule associated protein (MAP)-Tau, and peroxisome proliferator-activated receptor gamma (PPARgamma). Furthermore, the lipid profile and oxidative stress were ameliorated significantly by the course of treatment. In conclusion, the synthesized flavone has significant capability to promote neuroprotective effects in diabetes associated neurodegeneration through mitigating oxidative stress and modulating the expression of the targeted genes, thereby alleviating neuronal injuries.