title: Wogonin suppresses TNF-alpha-induced MMP-9 expression by blocking the NF-kappaB activation via MAPK signaling pathways in human aortic smooth muscle cells.
abstract: Matrix metalloproteinase-9 (MMP-9) plays a major role in the pathogenesis of atherosclerosis and restenosis by regulating both migration and proliferation of vascular smooth muscle cells (VSMC) after an arterial injury. In this study, we examined the inhibitory effect of three major flavonoids in Scutellariae Radix, baicalin, baicalein, and wogonin, on TNF-alpha-induced MMP-9 expression in human aortic smooth muscle cells (HASMC). Wogonin, but not baicalin and baicalein, significantly and selectively suppressed TNF-alpha-induced MMP-9 expression in HASMC. Reporter gene, electrophoretic mobility shift, and Western blotting assays showed that wogonin inhibits MMP-9 gene transcriptional activity by blocking the activation of NF-kappaB via MAPK signaling pathways. Moreover, the Matrigel migration assay showed that wogonin reduced TNF-alpha-induced HASMC migration. These results suggest that wogonin effectively suppresses TNF-alpha-induced HASMC migration through the selective inhibition of MMP-9 expression and represents a potential agent for the prevention of vascular disorders related to the migration of VSMC.
authors.affiliation: Department of Food Science and Technology and The Center for Traditional Microorganism Resources (TMR), Keimyung University, 1000 Sindang-Dong, Dalseo-Gu, Daegu 704-701, Republic of Korea.
authors.forename: Syng-Ook
authors.initials: SO
authors.lastname: Lee
authors.forename: Yun-Jeong
authors.initials: YJ
authors.lastname: Jeong
authors.forename: Mi Hee
authors.initials: MH
authors.lastname: Yu
authors.forename: Ji-Won
authors.initials: JW
authors.lastname: Lee
authors.forename: Mi Hyang
authors.initials: MH
authors.lastname: Hwangbo
authors.forename: Cheorl-Ho
authors.initials: CH
authors.lastname: Kim
authors.forename: In-Seon
authors.initials: IS
authors.lastname: Lee
mesh_terms: D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004789:Enzyme Activation / Q000187:drug effects; D044950:Flavanones / Q000008:administration & dosage*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage*
chemical_list: D004338:Drug Combinations; D044950:Flavanones; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D020780:Matrix Metalloproteinase 9; C085514:wogonin