Isoflavone genistein and daidzein up-regulate LPS-induced inducible nitric oxide synthase activity through estrogen receptor pathway in RAW264.7 cells

Mako Nakaya, Hirofumi Tachibana, Koji Yamada

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Isoflavones, such as genistein and daidzein, are found in abundance in soybeans. These plant-derived substances have estrogenic activities and can bind to the estrogen receptors (ERs). In this study, we investigated that the effects of 17β-estradiol (E2), genistein and daidzein on nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) activity in RAW264.7 cells. We found that these isoflavones significantly increased lipopolysaccharide-induced NO production and iNOS expression as much as E2 at physiological concentrations. Moreover, E2 and isoflavone enhanced the production of tumor necrosis factor-α that is one of the important cytokines regarding NO production. The enhancing effects of E2 and isoflavones on NO production were markedly inhibited by not only NG-nitro-l- arginine methyl ester (an inhibitor of NOS), but also ICI 182780 (ERs antagonist). Two types of ERs were identified as ERα and ERβ. An ERα agonist could increase iNOS expression in RAW264.7 cells, while an ERβ agonist could not. In conclusion, our results suggest E2, genistein and daidzein activate iNOS, and then up-regulate NO production. This enhancing effect is aroused through ERα pathway in RAW264.7 cells.

Original languageEnglish
Pages (from-to)108-114
Number of pages7
JournalBiochemical Pharmacology
Volume71
Issue number1-2
DOIs
Publication statusPublished - Dec 19 2005

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Isoflavones
Genistein
Nitric Oxide Synthase Type II
Estrogen Receptors
Nitric Oxide
Up-Regulation
Estrogens
Soybeans
Lipopolysaccharides
Estradiol
Tumor Necrosis Factor-alpha
daidzein
Cytokines

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Pharmacology

Cite this

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title = "Isoflavone genistein and daidzein up-regulate LPS-induced inducible nitric oxide synthase activity through estrogen receptor pathway in RAW264.7 cells",
abstract = "Isoflavones, such as genistein and daidzein, are found in abundance in soybeans. These plant-derived substances have estrogenic activities and can bind to the estrogen receptors (ERs). In this study, we investigated that the effects of 17β-estradiol (E2), genistein and daidzein on nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) activity in RAW264.7 cells. We found that these isoflavones significantly increased lipopolysaccharide-induced NO production and iNOS expression as much as E2 at physiological concentrations. Moreover, E2 and isoflavone enhanced the production of tumor necrosis factor-α that is one of the important cytokines regarding NO production. The enhancing effects of E2 and isoflavones on NO production were markedly inhibited by not only NG-nitro-l- arginine methyl ester (an inhibitor of NOS), but also ICI 182780 (ERs antagonist). Two types of ERs were identified as ERα and ERβ. An ERα agonist could increase iNOS expression in RAW264.7 cells, while an ERβ agonist could not. In conclusion, our results suggest E2, genistein and daidzein activate iNOS, and then up-regulate NO production. This enhancing effect is aroused through ERα pathway in RAW264.7 cells.",
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