فهرست نشریات علمی دسترسی آزاد ایران

Litsea angulata is a medicinal plant with promising bioactive metabolites, yet its antidiabetic mechanism remains insufficiently understood. This study investigated the antidiabetic potential of Litsea angulata leaf metabolites using an integrated approach combining LC–MS/MS profiling, network pharmacology, molecular docking, molecular dynamics (MD), and MM-PBSA analyses. Dried leaves were extracted by maceration with 70% ethanol and subjected to LC–MS/MS for metabolite annotation. Predicted compound targets were intersected with Type 2 Diabetes Mellitus (T2DM)–related genes to identify shared targets, followed by protein–protein interaction network construction, hub gene screening using maximal clique centrality (MCC), and GO/KEGG enrichment analysis. Molecular docking was conducted against PIK3R1 (PDB ID: 5XGJ), and the best-scoring complexes were evaluated by 50 ns MD simulations using GROMACS 2016.3. Structural stability was assessed through RMSD, RMSF, Rg, SASA, RDF, and hydrogen bond analyses, while binding free energies were estimated using MM-PBSA. A total of 432 shared targets were identified, forming a densely connected network, with PIK3R1 ranked among the top hub proteins (MCC 972,203). Sitosterol (Mol10) exhibited strong docking affinity toward PIK3R1 with a binding energy of −9.39 kcal/mol and an inhibition constant of 131.46 nM, approaching the affinity of the native ligand (−9.18 kcal/mol; Ki 186.78 nM). MM-PBSA calculations supported these findings, yielding comparable binding free energies for the native ligand (−118.852 ± 14.208 kJ/mol) and sitosterol (−117.931 ± 17.955 kJ/mol). These results suggest that Litsea angulata , particularly sitosterol, may modulate PI3K-related signaling pathways through stable interactions with PIK3R1.