Ultrapure and potent tannic acid (UPPTA) is a novel inhibitor of D-amino acid oxidase to improve the N-methyl-D-aspartate function of CNS disorders

Abstract

Tannic acids (TAs), a group of polyphenols, have been used as a traditional Chinese medicine for millennia. Nevertheless, due to the complexity of TAs’ compositions, no studies have specifically focused on the relationship between the compositions and their biological activities. In this study, by applying HPLC-PDA-MS and NMR analyses of the compositions and a d-amino acid oxidase (DAAO) assay for biological activities, we discovered that the number of galloyl moieties was positively correlated with the inhibitory potency of DAAO. Furthermore, the ultrapure and potent tannic acid (UPPTA) that we prepared by removing impurities and low-galloyl-moiety TAs exhibited the strongest DAAO inhibitory potency compared with all the commercial TAs. The in vivo studies using MK-801 treated mice showed that the UPPTA improved the N-methyl-d-aspartate (NMDA)-hypofunction-induced hyperactivity, working memory, and sensory motor gating deficits. In sum, the UPPTA demonstrated superior central nervous system (CNS) responses suggesting its potential as a novel therapeutic candidate for treating CNS disorders through DAAO inhibition.