Integrative Network Pharmacology and Glucose Uptake Studies Identify Potential Phytochemicals From <i>Syzygium cumini</i> as Promising Antidiabetic Agents

Diabetes mellitus (DM) is a multifaceted metabolic illness with significant detrimental effects during the conventional treatment approach. Therefore, this study aims to explore novel therapeutic targets and potential phytoconstituents using an edge-weighted network pharmacology approach. The bioactive compounds from Syzygium cumini were selected based on the literature evidence. Potential gene targets corresponding to these phytoconstituents were identified using gene-disease association, enrichment calculations, and KEGG pathway mapping analysis. These results reveal that PTPN1 is closely associated with the disease progression of DM. Binding interactions between phytochemicals and the candidate gene (PTPN1) were determined using molecular docking combined with molecular dynamics simulation and MM/PBSA calculations. Notably, chrysanthemin derived from S. cumini exhibited substantial inhibitory action in glucose uptake assays using L6 cell lines, PTP1B inhibition, and enzyme kinetics analyses. These findings suggest that this compound might be a promising candidate for PTPN1 inhibition, warranting further extensive research for its potential therapeutic application in DM.