Molecular docking and network pharmacology study on active compounds of Cyprus rotundus for the treatment of diabetes mellitus.

Abstract

Background: Diabetes Mellitus (DM) is a complex metabolic disorder with increasing global prevalence, necessitating the exploration of novel therapeutic strategies. Cyprus rotundus, a medicinal plant with a long history of traditional use, has shown promising potential in managing DM.

Aim of the study: This study aims to elucidate the mechanism of action of active components of C. rotundus in managing DM using a combination of network pharmacology and molecular docking approaches.

Materials and methods: The active compounds of C. rotundus were identified through IMPPAT and CHEBI database mining. Subsequently, compound-target are taken from swiss target prediction and SEA. Collection of DM-related targets is done through DisGeNET and TTD database. After identifying both the targets, common targets were evaluated through venny 2.1.0. by constructing venn diagram. To elucidate the potential targets of these compounds, a protein-protein interaction network was constructed by utilizing STRING database. Through network analysis, we identified key targets and pathways involved in the pathogenesis of DM and targeted by the active components of C. rotundus. Furthermore, molecular docking was performed to explore the binding affinity and interactions between the active compounds and their target proteins.

Results: This, reveal that the 12 active components of C. rotundus exert their therapeutic effects on DM through multiple mechanisms, there are 141 common target genes between C. rotundus and DM. Enrichment of the KEGG pathway mainly involves in the AGE-RAGE signaling pathway in diabetic complications, Type II DM pathway. Top 10 genes were regulated by C. rotundus in DM, including MMP9, PTGS2, CASP3, CD4, EGFR, STAT3, PPARG, AKT1, NFKB1 and MAPK3. Molecular docking analysis further validates the strong binding affinity between the active compounds and their target proteins, providing insights into their mode of action at the molecular level.

Conclusions: This study provides a systematic understanding of the mechanism of action of C. rotundus in managing DM, offering a basis for further experimental validation and drug development.