Unveiling the Anti-Colorectal Cancer Mechanisms of Libyan Artemisia herba-alba through Network Pharmacology, DFT, Molecular docking Approaches

Abstract

Colorectal cancer remains a leading cause of cancer-related mortality worldwide, and natural products have attracted interest as potential multi-target therapeutics. Artemisia herba-alba, a traditional medicinal plant in Libya, contains bioactive compounds such as quercetin, caffeic acid, chlorogenic acid, kaempferol, and luteolin, which may exert anticancer effects. This study aimed to investigate the potential mechanisms of these compounds against colorectal cancer using network pharmacology, protein–protein interaction analysis, GO and KEGG enrichment, and density functional theory (DFT) calculations. A total of 148 overlapping targets were identified, with core genes including STAT3, MAPK1, AKT1, EGFR, CDKN1A, CCND1, and TP53, which are involved in pathways regulating cell cycle, apoptosis, and tumor progression. Molecular docking results revealed that quercetin exhibited strong binding affinity with 6GUE (−8.9 kcal·mol⁻¹) through multiple hydrogen bonds and π-interactions, supporting its potential inhibitory role at the active site. DFT analysis of quercetin provided insights into its electronic properties and potential binding sites. Immunohistochemical data confirmed the overexpression of these targets in colorectal cancer tissues. Overall, the findings suggest that the bioactive compounds of A. herba-alba may exert multi-targeted anticancer effects by modulating key signaling pathways, highlighting their potential as therapeutic agents for colorectal cancer.