A novel perspective on the ameliorating effects of catechin-carbonyl adducts on AGEs toxicity

Advanced glycation end products (AGEs) are significant byproducts of the Maillard reaction and are implicated in degenerative diseases. Catechin (CC), a dietary polyphenol distributed in fruits and vegetables, inhibits AGEs formation through binding with carbonyl compounds. However, the biological role of these binding adducts remains unclear. This study first isolated the major CC-methylglyoxal (MGO) adducts using high-speed counter-current chromatography. Structural analysis confirmed it retains antioxidant phenolic hydroxyls. In food models (lactose/lysine and milk), CC-MGO significantly inhibited AGEs formation, an effect that may be partly attributed to its antioxidant activity. In Caco-2 cells, CC-MGO alleviated AGEs-induced cytotoxicity. Transcriptomics revealed AGEs activated the AGE-RAGE pathway (upregulating CXCL8, CCL2), while CC-MGO counteracted toxicity by modulating PPAR and IL-17 pathways, specifically upregulating SLC27A5 and downregulating MMP1 and PCK1. These findings demonstrate that CC not only scavenges carbonyls but also forms bioactive adducts that further suppress AGEs formation and toxicity, providing a dual mechanism for natural intervention. • CC-MGO adducts retain antioxidant phenolic hydroxyls. • CC-MGO adducts inhibit AGEs formation in food models via antioxidant activity. • CC-MGO adducts alleviate AGEs-induced cytotoxicity in Caco-2 cells. • CC-MGO adducts modulate PPAR/IL-17 pathways, downregulating MMP1/PCK1. • Catechin offers dual protection: scavenges carbonyls and forms bioactive adducts.