Alpha-Amylase Inhibition by Myricetin Nanoparticles: An in Silico, In Vitro, and In Vivo Evaluation toward Natural Antidiabetic Therapy

Purpose Diabetes mellitus is a worldwide health challenge, concern, and effective and affordably priced therapies are pivotal. Myricetin, a naturally occurring flavanol, has demonstrated promising antidiabetic potential. The current research aims to investigate the binding affinity and molecular interactions of myricetin with alpha-amylase and 1OSE protein, and to explore its potential as a therapeutic agent for diabetes management. Methods The present investigation, allied with molecular docking of myricetin against diabetes related targets, was investigated through Auto dock Vina, PyRx, and Schrodinger Glide. The target proteins were prepared in PDBQT format. Myricetin was docked to explore its molecular mechanism. The binding affinity and orientation of myricetin in the active site of alpha-amylase and 1OSE protein were evaluated. The in vivo antidiabetic potential of myricetin nanoparticles was assessed in Streptozotocin-induced diabetic Wistar rats. The experimental protocol was approved by the Institutional Animal Ethics Committee (IAEC) of Invitox R and D institute registration no.2273/PO/RERC/S/23 CCSEA, Report no. IRDI/IVAS/18/2024-25 registered under CPCSEA. The animals were randomly assigned to five groups (n = 6). Group I served as the normal control, while Group II received intraperitoneal Streptozotocin and was maintained as the untreated diabetic control. Groups III and IV were administered the test formulation (F1) orally at the selected doses, whereas Group V received the standard antidiabetic drug glibenclamide (5 mg/kg). The F1-treated groups exhibited a significant decrease in fasting blood levels of glucose compared with the diabetic control group, confirming in vivo antidiabetic efficacy of myricetin nanoparticles. Results Myricetin exhibited a strong and stable binding affinity toward alpha-amylase and 1OSE protein, with a binding energy of -8.8 to -7.6 kcal/mol. Molecular docking results revealed multiple hydrogen bonds and hydrophobic contacts between myricetin and critical residues within the catalytic pocket. Conclusion Myricetin exhibits promise as a therapeutic propensity for diabetes mitigation owing to its strong binding affinity and inhibitory activity against alpha-amylase.