title: Nobiletin suppresses MMP-9 expression through modulation of p38 MAPK activity in human dermal fibrobalsts.
abstract: We aimed to identify a novel flavonoid from the in-house natural products to suppress matrix metalloproteases (MMPs), which is responsible for degradation of collagen and other extracellular matrix proteins. Total eight natural products were screened for identification of a novel MMP-9 suppressor using MMP-9 reporter system, where the prompt initial screening with multiple samples is readily examined. Among the extracts used in the present study, one extract (Citrus unshiu) was found active in this assay system. Furthermore, three representative flavonoids in this active extract of Citrus unshiu peel were tested in MMP-9 reporter system. Nobiletin (NB) of the tested flavonoids suppressed MMP-9 expression without cytotoxicity, which was validated by both real-time polymerase chain reaction (PCR) and zymography analyses. Sustained p38 mitogen activated protein kinase (MAPK) activity, closely associated with induction of MMP-9 under stress condition, was markedly reduced by NB treatment, which implies that modulation of p38MAPK by nobiletin is responsible for reduction of MMP9 expression. Hence, nobiletin, identified from MMP-9 reporter system based screening, may be further applied for the purpose of delaying collagen degradation in skin fibroblasts.
authors.affiliation: Department of Life Science, College of Natural Science, Sogang University.
authors.forename: Jin-Ju
authors.initials: JJ
authors.lastname: Kim
authors.forename: Sovannarith
authors.initials: S
authors.lastname: Korm
authors.forename: Won-Seok
authors.initials: WS
authors.lastname: Kim
authors.forename: Ok-Seon
authors.initials: OS
authors.lastname: Kim
authors.forename: Ji-Seon
authors.initials: JS
authors.lastname: Lee
authors.forename: Hyung-Geun
authors.initials: HG
authors.lastname: Min
authors.forename: Young-Won
authors.initials: YW
authors.lastname: Chin
authors.forename: Hyuk-Jin
authors.initials: HJ
authors.lastname: Cha
mesh_terms: D002957:Citrus / Q000737:chemistry*; D003094:Collagen / Q000187:drug effects / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D047309:Flavones / Q000494:pharmacology*; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology*; D012867:Skin / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D047309:Flavones; D010936:Plant Extracts; D003094:Collagen; C008661:nobiletin; D048051:p38 Mitogen-Activated Protein Kinases; D020780:Matrix Metalloproteinase 9