Miyabenol A inhibits LPS-induced NO production via IKK/IkappaB inactivation in RAW 264.7 macrophages: possible involvement of the p38 and PI3K pathways.
The anti-inflammatory effect of miyabenol A, a stilbene isolated from Vitis thunbergii, on lipopolysaccaride (LPS)-induced nitric oxide (NO) production in RAW264.7 macrophages was studied. Miyabenol A inhibited NO production (EC 50: 2.7 muM) and iNOS protein and mRNA expression in a parallel concentration-dependent manner. LPS-evoked NF-kappaB nuclear translocation and associated IkappaB degradation were abrogated by miyabenol A treatment. Phosphorylations of IKKalpha/beta, ERK1/2, JNK p38 MAPK, and Akt were observed in LPS-stimulated cells; nevertheless, miyabenol A selectively blocked IKKalpha/beta, p38, and Akt phosphorylation. Furthermore, LPS-stimulated IKKalpha/beta and Akt phosphorylation was abolished by p38 inhibitor SB203580. Wortmannin (a PI3K inhibitor) also attenuated LPS-induced IKKalpha/beta phosphorylation, although to a less extent than SB203580, but failed to affect p38 phosphorylation. These observations suggested that PI3K/Akt might lie downstream of p38 MAPK to coregulate LPS-induced IKKalpha/beta phosphorylation. Taken together, miyabenol A acted via interfering with p38 MAPK-related signal pathways to down-regulate IKK/IkappaB activation and NO production.
Ku
Kuei-Ting
KT
Institute of Life Science, College of Science and Engineering, National Taitung University, Taitung.
Huang
Yu-Ling
YL
Huang
Yu-Jou
YJ
Chiou
Wen-Fei
WF
D000818:Animals; D001572:Benzofurans / Q000494:pharmacology*; D002460:Cell Line; D015870:Gene Expression / Q000187:drug effects; D051550:I-kappa B Kinase / Q000378:metabolism; D020672:I-kappa B Proteins / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D018517:Plant Roots / Q000737:chemistry; D013267:Stilbenes / Q000302:isolation & purification / Q000494:pharmacology*; D027843:Vitis / Q000737:chemistry; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D001572:Benzofurans; D020672:I-kappa B Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D013267:Stilbenes; C533788:miyabenol A; D000072000:NF-KappaB Inhibitor alpha; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D019869:Phosphatidylinositol 3-Kinases; D051550:I-kappa B Kinase; D048051:p38 Mitogen-Activated Protein Kinases