Phenolic profiling unravels the chemopreventive components of Melaleuca citrina (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. Melaleuca citrina (Curtis) Dum.Cours. is an aromatic plant with significant medicinal value. The phenolic profiling of M. citrina 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 in silico 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.