Effects of Polyphenols, Including Flavonoids, on Glutathione S-Transferase and Glutathione Reductase

Abstract

Effects of twelve flavonoids and five catechins as well as gallic acid on two kinds of glutathione-related enzymes were investigated. Glutathione S-transferase (EC 2.5.1.18) activity was measured by S-2, 4-dinitrophenyl glutathione formation from 1-chloro-2, 4-dinitrobenzene and reduced glutathione. Glutathione reductase (EC 1.6.4.2) activity was followed by NADPH dehydrogenation. Fisetin and myricetin were potent inhibitors of glutathione S-transferase, while kaempferol, quercetin, baicalein, and quercitrin were medium inhibitors. Epicatechin gallate and epigallocatechin gallate also showed medium inhibition. Kinetic analyses indicated that fisetin was a mixed type inhibitor of glutathione S-transferase with respect to both substrates, while myricetin was a competitive inhibitor of the same enzyme with both substrates. Fisetin and myricetin were noncompetive inhibitors of glutathione reductase with both NADPH and oxidized glutathione. The inhibition patterns of GT and GR as well as the results of kinetic analyses indicated a possibility that inhibitory flavonoids might have some influence on the glutathione recognition sites of the two enzymes.