Abstract
Curcuma aromatica Salisb (Cur), a well-known herbal medicine, has a wide spectrum of anti-inflammatory, anticarcinogenic, and antioxidant activities. However, the roles of its active compounds and potential mechanisms in colorectal cancer remain unknown. This research utilized network pharmacology and experimental validation to explore the possible mechanisms by which Cur protects against colorectal cancer. The active compounds of Cur and related genes for colorectal cancer were obtained from public databases. The DrugBank database was used to search for anticolorectal cancer drugs licensed through the FDA and their targets, and a "drug-component-target" relationship network was created using the Cytoscape program. The String database produced the PPI network. The ability of these active ingredients to bind to core targets was confirmed by molecular docking using AutoDock Vina. Cell and animal experiments were then carried out. A total of 274 targets were obtained from Cur, 49 of which were potential therapeutic targets. Four key targets, PTGS2, AKT1, TP53, and estrogen receptor 1 (ESR1), were screened via the PPI network and the FDA drug-target network. Molecular docking results revealed that Cur had strong binding abilities to these targets. In vivo and in vitro experiments demonstrated that Cur suppressed the development of colorectal cancer by regulating its targets (PTGS2, AKT1, TP53, and ESR1), which play crucial roles in promoting apoptosis and suppressing cell proliferation, migration, and invasion. Collectively, Cur protects against colorectal cancer by regulating the AKT1/PTGS2/ESR1 and P53 pathways, which lays the groundwork for further research and clinical applications of Cur in colorectal cancer therapy.