Deciphering anti-colorectal cancer potential of Avicennia alba bioactives via network pharmacology and in vitro validation.

Colorectal cancer (CRC) remains a significant global health challenge, with the current therapies often being inadequate. This study investigates the potential of Avicennia alba (A. alba), a mangrove plant, as a source of new anticancer drug candidates. We employed a network pharmacology, bioinformatics approach, and in vitro experimental to explore the molecular mechanisms of action and validating activity of A. alba in CRC treatment. Cytotoxicity effect was also evaluated using MTT assay. Four constituents of A. alba-Avicenol B, Avicenol C, Avicequinone B, and Avicequinone C-were verified, leading to the identification of 10 hub genes (i.e., EGFR, PIK3CA, JAK2, MTOR, JUN, ERBB2, IGF2, SRC, MDM2, and PARP1) associated with CRC. Molecular docking and molecular dynamics simulations indicated that Avicequinone C exhibited the best docking scores and stable interactions with the top three hub genes (EGFR, PIK3CA, and JAK2). The interactions were characterized by π-sigma, alkyl, and conventional hydrogen bonds. A. alba exhibited cytotoxic activity against WiDr cell lines with an IC of 205.96 ± 24.05 μg/mL after treatment for 48 h. Our findings highlight potential therapeutic targets for A. alba in CRC treatment and demonstrate that integrating network pharmacology, bioinformatics, and molecular docking with in vitro experimental validation is an effective strategy for discovering new therapeutic targets in drug development.