In Silico Investigation of Bioactive Compounds in Royal Jelly Targeting α-Glucosidase for Potential Antidiabetic Therapy

Abstract

Abstract:

Background: Diabetes mellitus is one of the most significant global health challenges. Royal jelly (RJ), a bee product rich in bioactive components, has long been recognized for its functional health benefits. One strategy in the management of type 2 diabetes is to inhibit carbohydrate-digesting enzymes to control postprandial blood glucose levels. Although RJ is known to have positive metabolic effects, the specific mechanisms of its constituent components as inhibitors of key diabetes enzymes still require further exploration.

Objective: This study aims to investigate the potential of bioactive components in RJ as antidiabetic agents through the mechanism of α-glucosidase inhibition to support the development of new natural-based drugs.

Methods: The α-glucosidase protein structure, ligand preparation, and molecular docking simulations were performed using YASARA software. Protein structure quality was evaluated using a Ramachandran plot to ensure model validity. After the docking process was completed, the best inhibitor candidates were identified based on binding energy and molecular interactions, followed by Absorption, Distribution, Metabolism, and Excretion (ADMET) profiling. Molecular dynamics (MD) with Normal Mode Analysis (NMA) techniques were used to determine the deformability and rigidity of the complex.

Result: The target protein in this study is of high quality. Therefore, it was used for docking studies, and the results showed that acarbose, used as a positive control, was outperformed by two test ligands, diflucortolone and acetylsulfamethoxazole, with binding energies of 8.202 and 7.497 kcal/mol, respectively. Furthermore, the stability of the α-glucosidase-test ligand complex indicates a stable conformation as shown by molecular dynamics simulations using iMODS.

Conclusion: Based on docking evaluations, ADMET studies, it can be concluded that the components in royal jelly, particularly 10-HDA, have strong potential to be developed as antidiabetic drug candidates. Laboratory validation through in vitro is essential to confirm these findings before proceeding to the clinical phase.