Exploring synergistic inhibitory mechanisms of flavonoid mixtures on α-glucosidase by experimental analysis and molecular dynamics simulation
Junkun Pan, Muhammad Nawaz, Jiechao Liu, Hui Liu, Zhenzhen Lv, Wenbo Yang, Zhonggao Jiao, Qiang Zhang
Abstract
The study was the first to evaluate the synergistic interaction of luteolin + quercetin, luteolin + 3-O-methylquercetin, and quercetin + 3-O-methylquercetin mixtures on α-glucosidase and the binding mechanisms were explored using both experimental and theoretical approaches. The results showed that three flavonoid mixtures exhibited a mixed type of inhibition and demonstrated the most potent synergistic effects on α-glucosidase inhibition at 6:4 ratio, with interaction index (γ) of 0.85, 0.78 and 0.73, respectively. The three mixtures had a great influence on α-glucosidase secondary structures. Molecular simulation further demonstrated that three flavonoid mixtures formed hydrophobic interactions and hydrogen bonds with amino acid residues at different sites of α-glucosidase. Collectively, luteolin + quercetin, luteolin + 3-O-methylquercetin and quercetin + 3-O-methylquercetin were found to inhibit α-glucosidase in a synergistic manner and can be potentially used for the development of hypoglycemic food products.