Flavonoids as Natural Inhibitors of β-Carbolines: Mechanistic Insights.

The inhibitory mechanisms of flavonoids suppressing the formation of foodborne β-carboline heterocyclic amines, Harman and Norharman, remain unclear. In this study, structure-activity and correlation analyses linked the distinct inhibitory effects of spice-containing flavonoids on β-carboline formation (13.36-86.98%) to their phenolic hydroxyl groups and antioxidant capacity. The pronounced decrease in free radicals and reduced consumption of tetrahydro-β-carbolines (THβCs) in flavonoid-containing model systems indicated a radical scavenging mechanism that prevented the oxidation of THβC into β-carbolines. Concurrently, the significant reductions in formaldehyde, acetaldehyde, and THβCs levels revealed an additional pathway that flavonoids captured aldehydes to form adducts, thus diminishing THβC formation. Two major adducts, tryptophan-formaldehyde-flavonoid and flavonoid-formaldehyde-flavonoid, were identified by UPLC-MS/MS analysis. These mechanisms were verified in soy sauce brine systems, though their inhibitory efficacy was weakened by preexisting THβCs and β-carbolines, and the limited aqueous solubility of hydrophobic flavonoids. This work deepens insight into flavonoid-mediated inhibition of β-carboline formation and underscores their prospective application in controlling foodborne toxicants.