Abstract

Wogonin (Wog; 5,7-dihydroxy-8-methoxy flavone) has been shown to effectively inhibit lipopolysaccharide (LPS)-induced inducible nitric oxide synthase (iNOS) gene expression and nitric oxide production in our previous study. In the present study, we found that Nor-wogonin (N-Wog; 5,7,8-trihydroxyl flavone), a structural analogue of Wog with an OH substitution at C8, performed different effect on LPS- or lipoteichoic acid (LTA)-induced iNOS gene expression and nitric oxide (NO) production in macrophages. Wog, but not N-Wog, significantly inhibits LPS- or LTA-induced NO production through suppressing iNOS gene expression at both protein and mRNA without affecting NO donor sodium nitroprusside-induced NO production, NOS enzyme activity, and cells viability. Activation of JNKs (not ERKs) via phosphorylation induction, and an increase in c-Jun (not c-Fos) protein expression were involved in LPS- and LTA-treated RAW264.7 cells, and those events were blocked by Wog, but not N-Wog, addition. Furthermore, 5,7-diOH flavone, but not 5-OH flavone, 7-OH flavone, 5-OH-7-OCH3 flavone, significantly inhibits LPS-induced iNOS protein expression and NO production, and 7,8-diOCH3 flavone performs more effective inhibitory activity on LPS-induced NO production and iNOS protein expression than 7-OCH3-8-OH flavone. These data suggest that OHs at both C5 and C7 are essential for NO inhibition of flavonoids, and OCH3 at C8 may contribute to this activity, and suppression of JNKs-c-Jun activation is involved.

Original languageEnglish
Pages (from-to)1054-1063
Number of pages10
JournalInternational Immunopharmacology
Volume7
Issue number8
DOIs
Publication statusPublished - Aug 2007

Fingerprint

flavone
Nitric Oxide Synthase Type II
Lipopolysaccharides
Nitric Oxide
Macrophages
Gene Expression
Proto-Oncogene Proteins c-fos
Proteins
Nitric Oxide Donors
norwogonin
wogonin
lipoteichoic acid
Nitroprusside
Flavonoids

Keywords

  • iNOS
  • JNKs
  • LPS
  • LTA
  • NO
  • Nor-wogonin
  • Wogonin

ASJC Scopus subject areas

  • Immunology
  • Pharmacology

Cite this

@article{e2dac0a2aea94e6598333e636e901b0c,
title = "Wogonin but not Nor-wogonin inhibits lipopolysaccharide and lipoteichoic acid-induced iNOS gene expression and NO production in macrophages",
abstract = "Wogonin (Wog; 5,7-dihydroxy-8-methoxy flavone) has been shown to effectively inhibit lipopolysaccharide (LPS)-induced inducible nitric oxide synthase (iNOS) gene expression and nitric oxide production in our previous study. In the present study, we found that Nor-wogonin (N-Wog; 5,7,8-trihydroxyl flavone), a structural analogue of Wog with an OH substitution at C8, performed different effect on LPS- or lipoteichoic acid (LTA)-induced iNOS gene expression and nitric oxide (NO) production in macrophages. Wog, but not N-Wog, significantly inhibits LPS- or LTA-induced NO production through suppressing iNOS gene expression at both protein and mRNA without affecting NO donor sodium nitroprusside-induced NO production, NOS enzyme activity, and cells viability. Activation of JNKs (not ERKs) via phosphorylation induction, and an increase in c-Jun (not c-Fos) protein expression were involved in LPS- and LTA-treated RAW264.7 cells, and those events were blocked by Wog, but not N-Wog, addition. Furthermore, 5,7-diOH flavone, but not 5-OH flavone, 7-OH flavone, 5-OH-7-OCH3 flavone, significantly inhibits LPS-induced iNOS protein expression and NO production, and 7,8-diOCH3 flavone performs more effective inhibitory activity on LPS-induced NO production and iNOS protein expression than 7-OCH3-8-OH flavone. These data suggest that OHs at both C5 and C7 are essential for NO inhibition of flavonoids, and OCH3 at C8 may contribute to this activity, and suppression of JNKs-c-Jun activation is involved.",
keywords = "iNOS, JNKs, LPS, LTA, NO, Nor-wogonin, Wogonin",
author = "Huang, {Guan Cheng} and Jyh-Ming Chow and Shing-Chuan Shen and Liang-Yo Yang and Cheng-Wei Lin and Yen-Chou Chen",
year = "2007",
month = "8",
doi = "10.1016/j.intimp.2007.04.001",
language = "English",
volume = "7",
pages = "1054--1063",
journal = "International Immunopharmacology",
issn = "1567-5769",
publisher = "Elsevier",
number = "8",

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TY - JOUR

T1 - Wogonin but not Nor-wogonin inhibits lipopolysaccharide and lipoteichoic acid-induced iNOS gene expression and NO production in macrophages

AU - Huang, Guan Cheng

AU - Chow, Jyh-Ming

AU - Shen, Shing-Chuan

AU - Yang, Liang-Yo

AU - Lin, Cheng-Wei

AU - Chen, Yen-Chou

PY - 2007/8

Y1 - 2007/8

N2 - Wogonin (Wog; 5,7-dihydroxy-8-methoxy flavone) has been shown to effectively inhibit lipopolysaccharide (LPS)-induced inducible nitric oxide synthase (iNOS) gene expression and nitric oxide production in our previous study. In the present study, we found that Nor-wogonin (N-Wog; 5,7,8-trihydroxyl flavone), a structural analogue of Wog with an OH substitution at C8, performed different effect on LPS- or lipoteichoic acid (LTA)-induced iNOS gene expression and nitric oxide (NO) production in macrophages. Wog, but not N-Wog, significantly inhibits LPS- or LTA-induced NO production through suppressing iNOS gene expression at both protein and mRNA without affecting NO donor sodium nitroprusside-induced NO production, NOS enzyme activity, and cells viability. Activation of JNKs (not ERKs) via phosphorylation induction, and an increase in c-Jun (not c-Fos) protein expression were involved in LPS- and LTA-treated RAW264.7 cells, and those events were blocked by Wog, but not N-Wog, addition. Furthermore, 5,7-diOH flavone, but not 5-OH flavone, 7-OH flavone, 5-OH-7-OCH3 flavone, significantly inhibits LPS-induced iNOS protein expression and NO production, and 7,8-diOCH3 flavone performs more effective inhibitory activity on LPS-induced NO production and iNOS protein expression than 7-OCH3-8-OH flavone. These data suggest that OHs at both C5 and C7 are essential for NO inhibition of flavonoids, and OCH3 at C8 may contribute to this activity, and suppression of JNKs-c-Jun activation is involved.

AB - Wogonin (Wog; 5,7-dihydroxy-8-methoxy flavone) has been shown to effectively inhibit lipopolysaccharide (LPS)-induced inducible nitric oxide synthase (iNOS) gene expression and nitric oxide production in our previous study. In the present study, we found that Nor-wogonin (N-Wog; 5,7,8-trihydroxyl flavone), a structural analogue of Wog with an OH substitution at C8, performed different effect on LPS- or lipoteichoic acid (LTA)-induced iNOS gene expression and nitric oxide (NO) production in macrophages. Wog, but not N-Wog, significantly inhibits LPS- or LTA-induced NO production through suppressing iNOS gene expression at both protein and mRNA without affecting NO donor sodium nitroprusside-induced NO production, NOS enzyme activity, and cells viability. Activation of JNKs (not ERKs) via phosphorylation induction, and an increase in c-Jun (not c-Fos) protein expression were involved in LPS- and LTA-treated RAW264.7 cells, and those events were blocked by Wog, but not N-Wog, addition. Furthermore, 5,7-diOH flavone, but not 5-OH flavone, 7-OH flavone, 5-OH-7-OCH3 flavone, significantly inhibits LPS-induced iNOS protein expression and NO production, and 7,8-diOCH3 flavone performs more effective inhibitory activity on LPS-induced NO production and iNOS protein expression than 7-OCH3-8-OH flavone. These data suggest that OHs at both C5 and C7 are essential for NO inhibition of flavonoids, and OCH3 at C8 may contribute to this activity, and suppression of JNKs-c-Jun activation is involved.

KW - iNOS

KW - JNKs

KW - LPS

KW - LTA

KW - NO

KW - Nor-wogonin

KW - Wogonin

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