Sentot Joko Raharjo, Teti Estiasih, Ernanin Dyah Wijayanti, Dewi Ratih Tirto Sari, Yantty Maryanty
Stevia (Stevia rebaudiana), with its intense sweetness, therapeutic properties, and safety profile, serves not only as a sugar substitute but also promotes holistic metabolic health. This study aimed to investigate secondary metabolite compounds in stevia, particularly diterpenoids, and their potential as alpha-amylase and alpha-glucosidase inhibitors through molecular docking and dynamics simulations for antidiabetic therapy. The methodology included: extraction, maceration-sonification of stevia simplicia water extract; compound analysis, qualitative and quantitative profiling of stevia water extract via LC-MS; and in silico studies: molecular docking and dynamics simulations to evaluate diterpenoid interactions with alpha-amylase and alpha-glucosidase enzymes. Analysis identified 33 diterpenoid compounds, including, including ent-Kaurane diterpenoid steviol glycoside rebaudioside (34%); labdane diterpenoid (22%), tetracyclic diterpenoid (19%), ent-Kaurene diterpenoid stevioside (11%), diterpenoid glucoside (8%), and others (6%). Enzyme Inhibition, all 33 diterpenoids exhibited inhibitory activity against alpha-glucosidase and alpha-amylase. Binding Energy (MMGBSA): stevioside-alpha-glucosidase complex (ΔG: -45.6658 ± 4.0256 kcal/mol) and rebaudioside-S-alpha-amylase complex (ΔG: -3.1122 ± 4.3667 kcal/mol). The aqueous stevia extract contains 33 diterpenoids with dual inhibitory potential against alpha-amylase and alpha-glucosidase. Molecular dynamics simulations highlighted stevioside as the most potent alpha-glucosidase inhibitor and rebaudioside-S as the optimal alpha-amylase inhibitor, underscoring their therapeutic relevance in diabetes management. © 2025 by the authors.
Polytechnique of Health of Putra Indonesia Malang, Pharmacy and Food Analyst Department, East Java, Malang, Indonesia; Brawijaya University, Food Science and Biotechnology Department, East Java, Malang, Indonesia; Polytechnique of Health of Putra Indonesia Malang, Pharmacy Department, East Java, Malang, Indonesia; Ibrahimy University, Pharmacy Department, East Java, Situbondo, Indonesia; State Polytechnic of Malang, Chemical Engineering, East Java, Malang, Indonesia
