Phenolic profiling unravels the chemopreventive components of <i>Melaleuca citrina</i> (Curtis) Dum.Cours. fruits by integrating LC-MS/MS, in vitro studies, docking and molecular dynamic simulation

Chemoprevention is one of the most effective strategies for reducing the global prevalence of cancer. <i>Melaleuca citrina</i> (Curtis) Dum.Cours. is an aromatic plant with significant medicinal value. The phenolic profiling of <i>M. citrina</i> fruit extract (MCE) using LC-ESI-MS/MS, identified 22 phenolic components. The chemopreventive effect of MCE was evaluated by measuring the induction of NAD(P)H: quinone oxidoreductase 1 (NQO1) in murine hepatoma (Hepa1-c1c7) cells. MCE significantly induced the expression of NQO1 in a concentration-dependent manner, achieving a 2.0 ± 0.1-fold increase at 100 µg/mL. Western blot analysis confirmed the enzyme-inducing activity of MCE at the protein expression level. The <i>in silico</i> docking and molecular dynamic simulations of selected components supported the experimental findings by demonstrating interactions with the Keap1-Nrf2 complex, which is involved in NQO1 regulation. These findings provide a foundation for further research on the chemopreventive components of MCE as potential future therapeutic agents for cancer prevention.