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.