Study on Biological Defense Function though Regulation of Drug Metabolism System by Food Factors

(JSNFS Award for Young Investigators (2022))

Abstract

Toxicological effects of polycyclic aromatic hydrocarbons (PAHs) are mediated mainly by the aryl hydrocarbon receptor (AhR). Therefore, reduction of AhR activity is a promising strategy for prevention of xenobiotic-induced toxicity. Activation of nuclear factor-erythroid 2-related factor 2 (Nrf2) results in enhanced antioxidant capacity and protection against environmental stressors by inducing phase II drug-metabolizing enzymes. The author revealed that luteolin and kaempferol coordinately prevent AhR-induced phase I drug-metabolizing enzyme, and a physiological concentration of luteolin, achievable from dietary consumption, activated Nrf2. Moreover, B[a]P-induced AhR activation caused lipid accumulation in the liver through circadian disruption; however, luteolin and kaempferol inhibited the circadian disruption caused by AhR activation. These results indicate that luteolin and kaempferol enhance biological defense function against xenobiotic-induced toxicity through the regulation of the drug metabolism system.