Inhibition of lipopolysaccharide-induced expression of inducible nitric oxide synthase and tumor necrosis factor-alpha by 2'-hydroxychalcone derivatives in RAW 264.7 cells.
In cultures of the murine macrophage cell line RAW 264.7, effects of four 2'-hydroxychalcone derivatives, 2'-hydroxy-4'-methoxychalcone (compound 1), 2',4-dihydroxy-4'-methoxychalcone (compound 2), 2',4-dihydroxy-6'-methoxychalcone (compound 3) and 2'-hydroxy-4,4'-dimethoxychalcone (compound 4), on lipopolysaccharide (LPS)-induced production of nitric oxide (NO) and tumor necrosis factor (TNF)-alpha were examined. Compounds 1, 2 and 3 at 3-30microM inhibited the production with almost the same potency. Compound 4 showed no inhibitory activity. Compounds 1, 2 and 3 at 3-30microM inhibited the LPS-induced expression of inducible nitric oxide synthase (iNOS) and TNF-alpha mRNA. To clarify the mechanism involved, effects of compounds 1, 2 and 3 on the activation of nuclear factor (NF)-kappaB and activator protein-1 (AP-1) were examined. Both the LPS-induced activation of NF-kappaB and AP-1 were blocked by compounds 1, 2 and 3 at 3-30microM. Moreover, the three compounds at such concentrations inhibited the LPS-induced IkappaB degradation and the phosphorylation of c-jun N-terminal kinase (JNK) and c-jun. These findings suggest that the inhibition of the LPS-induced production of NO and TNF-alpha by the 2'-hydroxychalcone derivatives is due to the inhibition of NF-kappaB and AP-1 activations.
Ban
Hyun Seung
HS
Laboratory of Pathophysiological Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba Aramaki, Aoba-ku, Sendai, Miyagi 980-8578, Japan.
Suzuki
Katsuya
K
Lim
Soon Sung
SS
Jung
Sang Hoon
SH
Lee
Sanghyun
S
Ji
Jun
J
Lee
Hye Seung
HS
Lee
Yeon Sil
YS
Shin
Kuk Hyun
KH
Ohuchi
Kazuo
K
D000818:Animals; D002460:Cell Line; D002599:Chalcone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D047188:Chalcones; D004347:Drug Interactions; D015870:Gene Expression / Q000187:drug effects; D020672:I-kappa B Proteins / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D009566:Nitrates / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II; D010766:Phosphorylation; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D047188:Chalcones; D020672:I-kappa B Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D009566:Nitrates; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; D002599:Chalcone; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; C013031:2'-hydroxychalcone