Phytochemical Profile, Antioxidant, Enzyme Inhibition, Acute Toxicity, In Silico Molecular Docking and Dynamic Analysis of Apis Mellifera Propolis as Antidiabetic Supplement

Abstract

AbstractThis study aims to identify the phytochemical profile of Apis mellifera propolis and explore the potential of its anti‐diabetic activity through inhibition of α‐amylase (α‐AE), α‐glucosidase(α‐GE), as well as novel antidiabetic compounds of propolis. Apis mellifera propolis extract (AMPE) exhibited elevated polyphenol 33.26±0.17 (mg GAE/g) and flavonoid (15.45±0.13 mg RE/g). It also indicated moderate strong antioxidant activity (IC50 793.09±1.94 μg/ml). This study found that AMPE displayed promising α‐AE and α‐GE inhibition through in vitro study. Based on LC–MS/MS screening, 18 unique AMPE compounds were identified, with majorly belonging to anthraquinone and flavonoid compounds. Furthermore, in silico study determined that 8 compounds of AMPE exhibited strong binding to α‐AE that specifically interacted with its catalytic residue of ASP197. Moreover, 2 compounds exhibit potential inhibition of α‐GE, by interacting with crucial amino acids of ARG315, ASP352, and ASP69. Finally, we suggested that 2,7‐Dihydroxy‐1‐(p‐hydroxybenzyl)‐4‐methoxy‐9,10‐dihydrophenanthrene and 3(3‐(3,4‐Dihydroxybenzyl)‐7‐hydroxychroman‐4‐one as novel inhibitors of α‐AE and α‐GE. Notably, these compounds were initially discovered from Apis mellifera propolis in this study. The molecular dynamic analysis confirmed their stable binding with both enzymes over 100 ns simulations. The in vivo acute toxicity assay reveals AMPE as a practically non‐toxic product with an LD50 value of 16,050 mg/kg. Therefore, this propolis may serve as a promising natural product for diabetes mellitus treatment.