Inhibition of digestive enzymes by tea polyphenols: enzymological and in silico studies (1045.34)

Abstract

Tea (Camellia sinensis) has shown anti‐obesity effects in animals. Tea polyphenols can inhibit digestive enzymes such as pancreatic lipase (PL), phospholipase A2 (PLA2), and trypsin in vitro. Our objective was to explore the mechanisms of inhibition by tea polyphenols by enzymology and in silico modeling. Theaflavin‐3,3’‐digallate (TFdiG), theaflavin‐3’‐gallate, theaflavin‐3‐gallate, and theaflavin inhibit PL with IC50 = 1.9, 4.2, 3.0, and 32.9 µM, respectively, indicating that the location of the galloyl ester is essential for inhibitory potency. TFdiG exhibits a mixed mode of inhibition. Theaflavins were found to bind to a pocket adjacent to the active site in PL; galloyl‐containing theaflavins are able to form a hydrogen bond with His264, which forms part of the catalytic triad. Similar interactions are predicted with green tea catechins. Catechins also inhibit PLA2. Modeling studies show that these compounds occupy a tunnel that leads to the active site and are stabilized by van der Waals bonds. This interaction is expected to result in noncompetitive inhibition. We found that (‐)‐epigallocatechin‐3‐gallate (EGCG) inhibited trypsin (IC50 = 193 µM) in a non‐competitive manner. Modeling studies show that EGCG interacts with amino acids around the active site and hinders substrate binding. These findings provide insight into the mechanisms by which tea polyphenols can inhibit key digestive enzymes.Grant Funding Source: NIH AT004678