Inhibitory effects of flavonoids on rabbit heart carbonyl reductase

The inhibitory effects of flavonoids (galangin, kaempferol, quercetin, myri cetin, morin, and taxifolin) on rabbit heart carbonyl reductase (RHCR) were investigated using 4-benzoylpyridine (4BP) as the substrate. The stereoche mical characteristics of the flavonoids were found to be a factor determini ng their inhibitory potencies toward RHCR, Furthermore, the lipophilicity, and the scavenging or antioxidative effects of the flavonoids were likely t o complicate the structure-activity relationship of their inhibitory effect s on RHCR, Quercetin inhibited RHCR uncompetitively with respect to NADPH a nd competitively with respect to 4BP, suggesting that it competes with 4BP at the substrate-binding site of RHCR. RHCR efficiently reduced benzoquinon es (1,4-benzoquinone and 2-methyl-1,4-benzoquinone) and naphthoquinones (1, 4-naphthoquinone and menadione), Galangin was a potent inhibitor of RHCR wh en menadione was used as the substrate, and prevented the formation of the superoxide anion radical in the presence of RHCR, NADPH, and menadione, Fla vonoids may be useful compounds for suppressing the cardiotoxicity of quino nes by inhibiting RHCR.