Elucidation of therapeutic targets and mechanisms of Clitoria ternatea L. in colorectal cancer inhibition using network pharmacology and bioinformatics approaches

Context: Colorectal cancer (CRC) remains one of the leading causes of cancer-related mortality worldwide, highlighting the need for novel targeted therapies. Clitoria ternatea (CT), a medicinal plant with diverse bioactive compounds, shows promising anticancer potential in preclinical studies, yet its molecular mechanisms in CRC remain poorly understood. Aims: To elucidate the anti-CRC mechanisms and potential therapeutic targets of CT compounds through integrated bioinformatics and network pharmacology approaches. Methods: Active CT compounds were obtained from the literature and screened for drug-likeness. CRC-associated targets from GeneCards were intersected with CT-related targets to identify overlapping candidates. Overlapping targets were analyzed using network pharmacology, Gene Ontology (GO), and KEGG pathway enrichment. Hub genes were validated through mRNA expression, pathological stage correlations, and molecular docking, followed by 100-ns molecular dynamics simulations to assess binding stability. Results: Thirty-two CT compounds and eleven potential CRC-related targets were identified, with CCND1 and HSP90AB1 emerging as central hub genes linked to the PI3K/AKT and CRC signaling pathways. Ellagic acid exhibited the strongest binding affinity to CCND1 (−8.3 kcal/mol) and HSP90AB1 (−9.5 kcal/mol), and maintained conformational stability during simulations, outperforming control ligands. These findings highlight the multi-target therapeutic potential of CT in CRC. Further in vitro studies are needed to investigate CCND1 and HSP90AB1 expression, cell proliferation, and apoptosis in CRC models. Conclusions: CT exhibits multi-target anti-CRC potential by modulating CCND1 and HSP90AB1, suggesting a mechanistic link to the PI3K/AKT signaling pathway. These results support further validation (in vitro and in vivo studies) of CT and ellagic acid as potential adjuvant CRC therapies.