Network pharmacology study to identify molecular pathways involved in the anti-diabetic activity of <i>Syzygium cumini</i> seed constituents

Diabetes is characterized by hyperglycemia and insulin resistance, which significantly increase the risk of morbidity and mortality. Syzygium cumini seeds have been used traditionally in the management of diabetes, though the precise molecular mechanisms underlying their effects are not yet fully understood. The present study aimed to elucidate the molecular mechanisms through which S. cumini seed extract exerts its beneficial effects in diabetes, employing a network pharmacology approach. The constituents of S. cumini seeds were identified from online databases. Eligible constituents were then used to identify target genes through four databases. Genes associated with diabetes were retrieved from two databases. The overlapping genes were selected as the target genes for further analysis. A protein–protein interaction network was constructed using Cytoscape and the STRING database, which helped identify hub genes. This network was then used to perform gene ontology and pathway enrichment analyses. Among the 66 identified constituents, 29 were eligible for inclusion in the analysis. Database screening revealed 986 genes targeted by the selected active constituents, with 392 genes associated with diabetes. Of these, 112 genes overlapped. Following network development, the top 10 hub genes with the highest degree scores were selected for pathway enrichment analysis. The pathway enrichment analysis indicated that S. cumini may exert beneficial effects in diabetes by modulating several pathways related to RNA-mediated miRNA transcription, AGE-RAGE signaling, and HIF-1 signaling through multiple genes. The underlying mechanisms may involve enhanced cellular responses to oxidative stress, improved oxidative stress metabolism, and an elevated anti-inflammatory response. The current study provides promising evidence of the beneficial effects of S. cumini seed therapy in the management of diabetes. The findings of this study offer a potential direction for future molecular research to confirm the efficacy of S. cumini seeds in diabetic conditions through the pathways described.