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Structural basis for polyphenol-mediated glycemic control: comparative study on catechin oligomerization and gallic
Yang Liu1, Gexin Liu1, Yingbo Zhao1
1College of Enology, Northwest A&F University, Yangling 712100, China.
Abstract:
Diabetes mellitus, a global health challenge characterized by chronic hyperglycemia, can be managed by inhibiting intestinal α-glucosidases. While wine-derived catechin and gallic acid exhibit hypoglycemic potential, their bioactivity is limited by low bioavailability and unclear metabolic fate. This study employed simulated digestion coupled with HPLC and HR-LC-MS/MS to investigate their gastrointestinal transformation. Results demonstrated that catechin polymerized into oligomers in gastric phase (monomer degradation ∼13 %), which were further cleaved to specific metabolites in the intestine. Gallic acid was markedly degraded (>97 %) in the intestine, yielding p-hydroxybenzoic acid and ferulic acids-like compound. Molecular docking predicted that both parent compounds and their digestive products could inhibit maltase-glucoamylase and sucrase-isomaltase, with the catechin-catechol pyran adduct showing the strongest interaction (-8.02 kcal/mol) compared to parent catechin (-6.59 kcal/mol). These findings demonstrate the generation bioactive metabolites and provide a computational mechanistic basis for polyphenol-mediated diabetes control via α-glucosidase inhibition.
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