Biologically active compounds of Shan yao: Molecular mechanisms and implications for gestational diabetes mellitus through network pharmacology and metabolic profiling

Shan yao (SY, Dioscorea opposita Thunb.), is a potential industrial crop with high-value bioactive components. It is traditionally used in Chinese medicine for diabetes-related symptoms. Gestational Diabetes Mellitus (GDM) is a specific form of diabetes characterized by abnormal glucose tolerance during pregnancy. However, the mechanisms by which SY manages GDM remain unclear. This study aimed to identify bioactive compounds and assess the mechanisms of SY in managing GDM. We employed computational biomedical modelling and screening to explore the potential pharmacodynamics of the chemical components of SY and their mechanisms. We identified a total of 71 SY phytochemicals and 101 GDM proteins, resulting in 7171 molecular docking interactions. ABCC8 emerged as a primary target due to its high ligand binding affinities (-7.6 kcal/mol) and association scores (0.57). After conducting virtual pharmacokinetic and toxicity prediction analyses to ensure selection of safe compounds, four complexes were prioritized for subsequent molecular dynamics simulations and analysis, which were conducted for 100 ns in triplicate. Certain chemical classes, such as steroids and flavonoids, exhibited strong binding with ABCC8. Notably, batatasin III and abscisic acid (ABA) emerged as promising ligand choices, displaying minimal structural deviations and stable positioning within the binding pocket. The confirmation of batatasin III and ABA in SY samples via LC-MS/MS assays provided further support for these findings. This study enhances our understanding of SY’s bioactive properties and supports its potential as a cultivated medicinal plant with industrial significance. Further experimental research is needed to validate these findings.