In vitro effects of myricetin, morin, apigenin, (+)-taxifolin, (+)-catechin, (-)-epicatechin, naringenin and naringin on cytochrome b5 reduction by purified NADH-cytochrome b5 reductase

Celik H., Kosar M., Arinc E.

TOXICOLOGY, vol.308, pp.34-40, 2013 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 308
  • Publication Date: 2013
  • Doi Number: 10.1016/j.tox.2013.03.013
  • Journal Name: TOXICOLOGY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.34-40
  • Erciyes University Affiliated: Yes

Abstract

tThe microsomal NADH-dependent electron transport system consisting of cytochrome b5 reductaseand cytochrome b5 participates in a number of physiologically important processes including lipidmetabolism as well as is involved in the metabolism of various drug and xenobiotics. In the presentstudy, we assessed the inhibitory effects of eight dietary flavonoids representing five distinct chemicalclasses on cytochrome b5 reduction by purified cytochrome b5 reductase. From the flavonoids tested,myricetin was the most potent in inhibiting cytochrome b5 reduction with an IC50value of 0.35 M.Myricetin inhibited b5 reductase noncompetitively with a Kiof 0.21 M with respect to cofactor NADH,and exhibited a non-linear relationship indicating non-Michaelis–Menten kinetic binding with respectto cytochrome b5. In contrast to the potent inhibitory activity of myricetin, (+)-taxifolin was found to bea weak inhibitor (IC50= 9.8 M). The remaining flavonoids were inactive within the concentration rangetested (1–50 M). Analysis of structure–activity data suggested that simultaneous presence of three OHgroups in ring B is a primary structural determinant for a potent enzyme inhibition. Our results suggestthat inhibition of the activity of this system by myricetin or myricetin containing diets may influence themetabolism of therapeutic drugs as well as detoxification of xenobiotics.

The microsomal NADH-dependent electron transport system consisting of cytochrome b5 reductase and cytochrome b5 participates in a number of physiologically important processes including lipid metabolism as well as is involved in the metabolism of various drug and xenobiotics. In the present study, we assessed the inhibitory effects of eight dietary flavonoids representing five distinct chemical classes on cytochrome b5 reduction by purified cytochrome b5 reductase. From the flavonoids tested, myricetin was the most potent in inhibiting cytochrome b5 reduction with an IC50 value of 0.35 mu M. Myricetin inhibited b5 reductase noncompetitively with a K-i of 0.21 mu M with respect to cofactor NADH, and exhibited a non-linear relationship indicating non-Michaelis-Menten kinetic binding with respect to cytochrome b5. In contrast to the potent inhibitory activity of myricetin, (+)-taxifolin was found to be a weak inhibitor (IC50 =.9.8 mu M). The remaining flavonoids were inactive within the concentration range tested (1-50 mu M). Analysis of structure-activity data suggested that simultaneous presence of three OH groups in ring B is a primary structural determinant for a potent enzyme inhibition. Our results suggest that inhibition of the activity of this system by myricetin or myricetin containing diets may influence the metabolism of therapeutic drugs as well as detoxification of xenobiotics. (c) 2013 Elsevier Ireland Ltd. All rights reserved.