Genistein as a potential inducer of the anti‐atherogenic enzyme paraoxonase‐1: studies in cultured hepatocytes in vitro and in rat liver in vivo

Journal of Cellular and Molecular Medicine

Charlotte Schrader¹  Insa M. A. Ernst¹  Heike Sinnecker¹  Sebastian T. Soukup²  Sabine E. Kulling² 

[1] Institute of Human Nutrition and Food Science, Christian-Albrechts-University of Kiel, Kiel, Germany;Department of Safety and Quality of Fruit and Vegetables, Max Rubner-Institut, Federal Research Institute of Nutrition and Food, Karlsruhe, Germany

关键词: aryl hydrocarbon receptor;    oestrogen receptor;    flavonoids;    genistein;    genistein metabolites;    oxidized LDL;    paraoxonase 1;   

DOI  :  10.1111/j.1582-4934.2012.01542.x

来源: Wiley

【 摘 要 】

Abstract

A number of cardioprotective effects, including the reduced oxidation of the low-density lipoprotein (LDL) particles, have been attributed to dietary soy isoflavones. Paraoxonase 1 (PON1), an enzyme mainly synthesized in the liver, may exhibit anti-atherogenic activity by protecting LDL from oxidation. Thus, dietary and pharmacological inducers of PON1 may decrease cardiovascular disease risk. Using a luciferase reporter gene assay we screened different flavonoids for their ability to induce PON1 in Huh7 hepatocytes in culture. Genistein was the most potent flavonoid with regard to its PON1-inducing activity, followed by daidzein, luteolin, isorhamnetin and quercetin. Other flavonoids such as naringenin, cyanidin, malvidin and catechin showed only little or no PON1-inducing activity. Genistein-mediated PON1 transactivation was partly inhibited by the oestrogen-receptor antagonist fulvestrant as well as by the aryl hydrocarbon receptor antagonist 7-ketocholesterol. In contrast to genistein, the conjugated genistein metabolites genistein-7-glucuronide, genistein-7-sulfate and genistein-7,4′-disulfate were only weak inducers of PON1 transactivation. Accordingly, dietary genistein supplementation (2 g/kg diet over three weeks) in growing rats did not increase hepatic PON1 mRNA and protein levels as well as plasma PON1 activity. Thus, genistein may be a PON1 inducer in cultured hepatocytes in vitro, but not in rats in vivo.

【 授权许可】

Unknown   
© 2012 The Authors Journal of Cellular and Molecular Medicine © 2012 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd