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Structural specificity of flavonoids to selectively inhibit starch digestive enzymes for triggering the gut-brain axis

thesis
posted on 14.01.2021, 17:58 by Jongbin Lim

In this study, structural specificity of flavonoids was investigated toselectively inhibit starch digestive enzymes to stimulate the ileal-brake by triggering glucagon-like peptide-1 (GLP-1) through distal small intestine starch digestion which can regulate food intake and appetite. The double bond between C2 and C3 on flavonoid’s chemical structure plays a critical role to inhibit human pancreatic α-amylase, leading to π-staking interaction. Meanwhile, the hydroxyl group at C3 on the backbone benzopyran ring is intimately related to inhibition of the mucosal α-glucosidases. This selective inhibition is likely the result of fundamental differences in the protein structures of α-amylase and α-glucosidases, as they belong to different glycosyl hydrolase Families 13 and 31 (GH13 and GH31). α-Amylase has the catalytic active siteslocated in wide and shallow grooves on the protein structure, while α-glucosidases possess the narrow and deep catalytic pocket. In an acute study done on mice, luteolin, which had thehigher degree of selectivity toward α-amylase, showed a slow and sustained postprandial glycemic response with a reduced blood glucose peak and extended high glucose profile, compared to 3’,4’-dihydroxylflavonol as the selective α-glucosidases specific inhibitor. Quercetin was inhibitory of both α-amylase and α-glucosidases.Glycemic profiles in mice confirmed in vitro analysis of the inhibitory selectivity of the flavonoids tested. Additionally, the extended glycemic response with luteolin was accompaniedthe higher secretion of GLP-1 at extended postprandial times by delivering more starch portion into the distal small intestine where the ileal-brake and gut-brain axis activation takes place. Overall, selective inhibition of α-amylase by flavonoids potentially could be considered as a key approach to control glucose release from starch with slow and extended, but still complete, digestion for improved glycemic response and minimized adverse side effects that result from severely restricting or even shutting down starch digestion by pharmaceutical grade inhibitors.

History

Degree Type

Doctor of Philosophy

Department

Food Science

Campus location

West Lafayette

Advisor/Supervisor/Committee Chair

Bruce R. Hamaker

Additional Committee Member 2

Bradley L. Reuhs

Additional Committee Member 3

Mario G. Ferruzzi

Additional Committee Member 4

Owen G. Jones

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