Wogonin but not Nor-wogonin inhibits lipopolysaccharide and lipoteichoic acid-induced iNOS gene expression and NO production in macrophages.
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-OCH(3) flavone, significantly inhibits LPS-induced iNOS protein expression and NO production, and 7,8-diOCH(3) flavone performs more effective inhibitory activity on LPS-induced NO production and iNOS protein expression than 7-OCH(3)-8-OH flavone. These data suggest that OHs at both C5 and C7 are essential for NO inhibition of flavonoids, and OCH(3) at C8 may contribute to this activity, and suppression of JNKs-c-Jun activation is involved.
Huang
Guan-Cheng
GC
Department of Internal Medicine, Chi-Mei Medical Center, Tainan, Taiwan.
Chow
Jyh-Ming
JM
Shen
Shing-Chuan
SC
Yang
Liang-Yo
LY
Lin
Cheng-Wei
CW
Chen
Yen-Chou
YC
D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D015153:Blotting, Western; D002460:Cell Line; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D044950:Flavanones / Q000737:chemistry / Q000494:pharmacology*; D047309:Flavones / Q000737:chemistry / Q000494:pharmacology; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000235:genetics; D020128:Inhibitory Concentration 50; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D015394:Molecular Structure; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D011794:Quercetin / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D031364:Scutellaria baicalensis / Q000737:chemistry; D013682:Teichoic Acids / Q000494:pharmacology*
D000873:Anthracenes; D044950:Flavanones; D047309:Flavones; D005419:Flavonoids; D008070:Lipopolysaccharides; D010936:Plant Extracts; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; C499814:Scutellaria baicalensis extract; D013682:Teichoic Acids; C432165:pyrazolanthrone; D009569:Nitric Oxide; C055505:norwogonin; C009900:lipoteichoic acid; D011794:Quercetin; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; C085514:wogonin; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one