Inhibition of lipopolysaccharide-induced expression of inducible nitric oxide synthase by butein in RAW 264.7 cells.
Butein has been reported to exert anti-inflammatory effect but the possible mechanism involved is still unclear. Here, we report the inhibitory effect of butein on nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) gene expression. Butein also inhibited the induction of tumor necrosis factor-alpha and cyclooxygenase 2 by LPS. To further investigate the mechanism responsible for the inhibition of iNOS gene expression by butein, we examined the effect of butein on LPS-induced nuclear factor-kappaB (NF-kappaB) activation. The LPS-induced DNA binding activity of NF-kappaB was significantly inhibited by butein, and this effect was mediated through inhibition of the degradation of inhibitory factor-kappaB and phosphorylation of Erk1/2 MAP kinase. Furthermore, increased binding of the osteopontin alphavbeta3 integrin receptor by butein may explain its inhibitory effect on LPS-mediated NO production. Taken together, these results suggest that butein inhibits iNOS gene expression, providing possible mechanisms for its anti-inflammatory action.
Lee
Sung Hee
SH
Medicinal Resources Research Center, College of Pharmacy, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea.
Seo
Geom Seog
GS
Sohn
Dong Hwan
DH
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002599:Chalcone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D047188:Chalcones; D051546:Cyclooxygenase 2; D003600:Cytosol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D007249:Inflammation; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D008070:Lipopolysaccharides / Q000737:chemistry*; D020935:MAP Kinase Signaling System; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000378:metabolism; D053495:Osteopontin; D010766:Phosphorylation; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D012795:Sialoglycoproteins / Q000378:metabolism
D047188:Chalcones; D039302:Integrin alphaVbeta3; D007527:Isoenzymes; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009573:Nitrites; D012795:Sialoglycoproteins; C506896:Spp1 protein, mouse; D053495:Osteopontin; C040918:butein; D002599:Chalcone; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3