Nobiletin-rich Citrus depressa Peel extract enhances detoxification-related responses and reduces benzo[a]pyrene bioaccumulation in rats.

Benzo[a]pyrene (B[a]P) is a carcinogenic food contaminant formed during thermal processing. Citrus depressa peel, a processing byproduct rich in polymethoxyflavones (PMFs) including nobiletin (NOB), was evaluated for detoxification-related effects in rats. C. depressa peel ethanol extract (CDHPE) was characterized, and its effects on xenobiotic metabolism and B[a]P disposition were assessed. NOB showed measurable oral bioavailability and multi-tissue distribution. Dietary CDHPE or NOB for 7 days increased hepatic phase I/II enzyme activities and intestinal CYP1A1 activity, accompanied by increased hepatic nuclear Nrf2 and reduced ROS levels. Pre-feeding reduced plasma B[a]P AUC by 57-79% and tissue burden by 30-80%, with increased urinary excretion of parent B[a]P. Upregulation of selected Nrf2 downstream target proteins (GCLC, HO-1, NQO1) and significant GCLC mRNA induction are consistent with Nrf2-associated detoxification responses, although causal confirmation by loss-of-function approaches remains needed. These findings support the potential use of citrus peel byproducts as functional ingredients for dietary PAH mitigation.