Abdullahi Musa, Nanik Siti Aminah, Muhammad Ikhlas Abdjan, Alfinda Novi Kristanti, Fadjar Mulya, Yoshiaki Takaya, Muggundha Raoov, Imam Siswanto, Geraldo Figo Hariyanto, Iffa Halimah Hasna
Diabetes mellitus remains a major global health challenge, and the discovery of novel α-glucosidase inhibitors from natural products offers a promising strategy for managing postprandial hyperglycemia. Although synthetic inhibitors such as acarbose are clinically effective, their gastrointestinal side effects drive the search for safer alternatives. A phytochemical investigation of Shorea beccariana led to the isolation of β-sitosterol (BS) and β-sitosterol-3-O-β-D-glucoside (BSG). Pharmacokinetic predictions indicated favorable drug-likeness and higher bioavailability scores for both compounds compared to acarbose. In vitro α-glucosidase inhibition assay showed that BSG (IC50 = 608.4 ± 0.09 µM) exhibited comparable inhibitory potency to acarbose (IC50 = 619.1 ± 0.30 µM), whereas BS (IC50 = 957.6 ± 0.10 µM) showed weaker activity. Molecular docking and molecular dynamics simulations further confirmed stable binding of both compounds within the enzyme’s active pocket, with BSG forming multiple hydrogen bonds and displaying the most favorable free binding energy (ΔGbind = −49.95 kcal/mol) based on the QM/MM-GBSA method. Collectively, this study not only identifies BSG as a promising natural α-glucosidase inhibitor but also provides the first mechanistic insight into phytosterols from S. beccariana as potential antidiabetic leads. Further in vivo validation and formulation strategies, such as cyclodextrin encapsulation, are recommended to enhance therapeutic potential. © The Author(s) 2026.
Department of Chemistry, Faculty of Science and Technology, Universitas Airlangga, East Java, Surabaya, 60115, Indonesia; Biotechnology of Tropical Medicinal Plants Research Group, Universitas Airlangga, East Java, Surabaya, 60115, Indonesia; Department of Chemistry, Faculty of Mathematics and Natural Science, Universitas Negeri Surabaya, East Java, Surabaya, 60231, Indonesia; Computational Health and Medicine Research Group, Institute of Tropical Disease, Universitas Airlangga, East Java, Surabaya, 60115, Indonesia; Faculty of Pharmacy, Meijo University, Aichi Prefecture, Nagoya, 4688502, Japan; Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur, 505603, Malaysia; Master Program of Basic Medical Science, Faculty of Medicine, Universitas Airlangga, Surabaya, 60115, Indonesia; Medical Study Program, Faculty of Medicine and Health, Institut Teknologi Sepuluh Nopember, Surabaya, 60111, Indonesia
