title: KIOM-79 inhibits LPS-induced iNOS gene expression by blocking NF-kappaB/Rel and p38 kinase activation in murine macrophages.
abstract: We demonstrate that KIOM-79, combined extracts obtained from Magnolia officinalis, Pueraria lobata, Glycyrrhiza uralensis, and Euphorbia pekinensis, inhibits LPS-induced expression of iNOS gene in RAW 264.7 cells. Treatment of RAW 264.7 cells with KIOM-79 inhibited LPS-stimulated nitric oxide production in a dose-related manner. Immunohisto-chemical staining of iNOS and RT-PCR analysis showed that the decrease of NO was due to the inhibition of iNOS gene expression. Immunostaining of p65, EMSA, and reporter gene assay showed that KIOM-79 inhibited NF-kappa/Rel nuclear translocation, DNA binding, and transcriptional activation, respectively. Western immunoblot analysis of p38 kinase showed KIOM-79 significantly inhibited the phosphoylation of p38 kinase which is important in the regulation of iNOS gene expression. Collectively, this series of experiments indicates that KIOM inhibits iNOS gene expression by blocking NF-kappa/Rel and p38 kinase signaling. Due to the critical role that NO release plays in mediating inflammatory responses, the inhibitory effects of KIOM-79 on iNOS suggest that KIOM-79 may represent a useful anti-inflammatory agent.
authors.affiliation: College of Medicine, Chosun University, 375 Susukdong, Kwangju 501-709, Republic of Korea.
authors.forename: Young Jin
authors.initials: YJ
authors.lastname: Jeon
authors.forename: Mei Hong
authors.initials: MH
authors.lastname: Li
authors.forename: Kun Yeong
authors.initials: KY
authors.lastname: Lee
authors.forename: Jin Sook
authors.initials: JS
authors.lastname: Kim
authors.forename: Ho Jin
authors.initials: HJ
authors.lastname: You
authors.forename: Seog Ki
authors.initials: SK
authors.lastname: Lee
authors.forename: Hong Moon
authors.initials: HM
authors.lastname: Sohn
authors.forename: Sang Joon
authors.initials: SJ
authors.lastname: Choi
authors.forename: Jae Woong
authors.initials: JW
authors.lastname: Koh
authors.forename: In Youb
authors.initials: IY
authors.lastname: Chang
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D002460:Cell Line; D004789:Enzyme Activation / Q000187:drug effects; D028481:Euphorbia / Q000737:chemistry; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D029882:Glycyrrhiza uralensis / Q000737:chemistry; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D031566:Magnolia / Q000737:chemistry; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics*; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D020569:Proto-Oncogene Proteins c-rel / Q000037:antagonists & inhibitors* / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: C517978:KIOM 79; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010936:Plant Extracts; D020569:Proto-Oncogene Proteins c-rel; D052247:Nitric Oxide Synthase Type II; D048051:p38 Mitogen-Activated Protein Kinases