Abstract
Polymethoxyflavones (PMFs) are investigated for their inhibitory mechanisms against heterocyclic aromatic amines (HAs) and advanced glycation end products (AGEs). Tangeretin, isosinensetin (ISN), 3',4',5,7-tetramethoxyflavone (TMHF), and their mixture dose-dependently suppressed the formation of PhIP, CML, and CEL, with ISN and the mixture showing the strongest activity. PMFs also effectively scavenged free radicals and reduced key intermediates, including phenylacetaldehyde, glyoxal (GO), and methylglyoxal (MGO). UPLC-TOF-MS analysis revealed novel GO/MGO-PMF adducts, indicating that PMFs trap α-dicarbonyl compounds via covalent binding. In silico toxicity prediction suggested these adducts have lower mutagenic potential and chronic oral toxicity than PhIP, CML, and CEL. Collectively, PMFs inhibit HAs and AGEs through a dual mechanism of radical scavenging and reactive intermediate trapping, transforming hazardous precursors into less toxic products. These findings support PMFs as effective and safe natural inhibitors for mitigating process-induced contaminants in thermally processed foods.