Abdullahi Musa, Muhammad Ikhlas Abdjan, Nanik Siti Aminah, Alfinda Novi Kristanti, I Gusti Made Sanjaya, Andika Pramudya Wardana, Shamsu Shuaibu Balah, Yoshiaki Takaya
A bioassay-guided phytochemical investigation of the endangered plant Shorea beccariana led to the isolation of two bioactive compounds: 3-O-methylellagic acid 3'-O-α-rhamnoside (EAG) and Bergenin (BER). Their structures were elucidated using a combination of 1D and 2D Nuclear Magnetic Resonance (NMR) spectroscopy, Ultraviolet–Visible (UV-Vis) spectrophotometry, and Fourier Transform Infrared (FTIR) analysis. The pharmacokinetic profiles of both compounds were evaluated through in silico Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET), bioavailability, and drug-likeness assessments, indicating favorable drug-like properties. In vitro α-glucosidase inhibitory activity assays revealed that EAG (IC₅₀ = 562.4 ± 0.11 µM) was slightly more potent than the reference inhibitor acarbose (IC₅₀ = 619.8 ± 0.03 µM), while BER (IC₅₀ = 1127.6 ± 0.09 µM) demonstrated a weaker inhibition. To further elucidate their mechanisms of action, molecular docking and molecular dynamics (MD) simulations were performed. Binding free energies (ΔG_bind), calculated via the Quantum Mechanics/Molecular Mechanics – Generalized Born Surface Area (QM/MM-GBSA) method, revealed strong interactions with α-glucosidase: EAG (-40.76 kcal/mol), BER (-34.53 kcal/mol), and acarbose (-33.86 kcal/mol). Notably, although BER was less potent than acarbose in vitro, its superior binding affinity in silico suggests potential benefits from molecular flexibility and dynamic stabilization. This study represents the first report of α-glucosidase inhibitory activity from S. beccariana and contributes valuable phytochemical and pharmacological insights that may support its conservation and therapeutic exploration. © The Author(s) 2025.
Department of Chemistry, Faculty of Science and Technology, Universitas Airlangga, Surabaya, 60115, Indonesia; Department of Chemistry, Faculty of Mathematics and Natural Science, Universitas Negeri Surabaya, Surabaya, 60231, Indonesia; Biotechnology of Tropical Medicinal Plants Research Group, Universitas Airlangga, Surabaya, 60115, Indonesia; Department of Chemistry, Rabiu Musa Kwankwaso College of Advance and Remedial Studies, Kano, 711102, Nigeria; Faculty of Pharmacy, Meijo University, Tempaku, Nagoya, 468-8502, Japan
