Neohesperidin and neohesperidin dihydrochalcone alleviated benzo[a]pyrene-induced toxicity: By inhibiting the activity of CYP1A1 enzyme.

Benzo(a)pyrene (BaP), a widespread environmental and food pollutant, induces cellular toxicity through CYP1A1-mediated metabolic activation. This study demonstrated that neohesperidin (NH) and neohesperidin dihydrochalcone (NHDC) effectively inhibited CYP1A1 activity. The recombinant CYP1A1 protein expressed in E. coli confirmed these inhibitory effects in vitro. Using a HepG2 cell model, both NH and NHDC significantly alleviated BaP-induced cytotoxicity and oxidative stress, as evidenced by enhanced cell viability and upregulated HO-1, NQO-1, and Nrf-2 expression. Comet assay results further showed that NH and NHDC reduced BaP-induced DNA damage. Molecular docking revealed stable binding interactions between NH, NHDC, and CYP1A1 active sites. Collectively, NH and NHDC attenuated BaP-induced hepatocellular injury in association with CYP1A1 inhibition and enhancement antioxidant defense. These findings highlight their potential as natural chemoprotective agents and demonstrate the value of molecular docking for identifying bioactive compounds with specific functional properties.