title: Increase of collagen synthesis by obovatol through stimulation of the TGF-beta signaling and inhibition of matrix metalloproteinase in UVB-irradiated human fibroblast.
abstract: BACKGROUND
  Alterations of the extracellular matrix (ECM) is critical in the photo and age-damaged skin. Thus any compounds keep ECM can protected from photo and aged-damaged skin. ECM is predominantly composed of type I and type III collagens in the dermis. Transforming growth factor (TGF-beta)s play important roles in cellular biosynthesis of extracellular matrix. Activator protein 1 (AP-1) and Smad are significant factors that mediate TGF-beta.
  
  
  OBJECTIVE
  We have investigated increasing effects of obovatol, a biphenolic compound isolated from leaves of Magnolia obovata on the collagen synthesis through stimulation of the TGF-beta signaling and inhibition of matrix metalloproteinase, thereby protect against from UV damages via maintain of collagen in the UVB irradiated human fibroblast cells.
  
  
  METHODS
  The fibroblasts were pretreated with obovatol for 24h and then the cells were irradiated with UVB. UVB-exposed cells were further cultured for 24h. Type I procollagen, MMP-3, TGF-beta and Smad as well as phosphorylation of MAPK family expression were determined by Western blot. The activation of AP-1 was investigated using EMSA. The released type I procollagen and TGF-beta into cell culture medium were determined by Western blot after concentration of these proteins.
  
  
  RESULTS
  The results showed that obovatol stimulated type I procollagen, TGF-beta, and Smad expression and inhibited matrix metalloproteinase-3 (MMP-3) in dose-dependent manner (1-5muM) in UVB-irradiated human fibroblast cells. Obovatol also inhibited UVB-induced activation of AP-1 and MAP kinases.
  
  
  CONCLUSIONS
  These results suggest that obovatol increases collagen synthesis through stimulation of the TGF-beta signaling and inhibition of matrix metalloproteinase in UVB-irradiated human fibroblast, thus obovatol could be effective against photo-damaged skin.
authors.affiliation: College of Pharmacy, Chungbuk National University, 48, Gaesin-dong, Heungduk-gu, Cheungju, Chungbuk 361-763, South Korea.
authors.forename: Myoung Suk
authors.initials: MS
authors.lastname: Choi
authors.forename: Myung Sik
authors.initials: MS
authors.lastname: Yoo
authors.forename: Dong Ju
authors.initials: DJ
authors.lastname: Son
authors.forename: Hai Young
authors.initials: HY
authors.lastname: Jung
authors.forename: Seung Ho
authors.initials: SH
authors.lastname: Lee
authors.forename: Jae Kyung
authors.initials: JK
authors.lastname: Jung
authors.forename: Beom Cheon
authors.initials: BC
authors.lastname: Lee
authors.forename: Yeo Pyo
authors.initials: YP
authors.lastname: Yun
authors.forename: Hyeong Bae
authors.initials: HB
authors.lastname: Pyo
authors.forename: Jin Tae
authors.initials: JT
authors.lastname: Hong
mesh_terms: D001713:Biphenyl Compounds / Q000302:isolation & purification / Q000494:pharmacology*; D002478:Cells, Cultured; D024042:Collagen Type I / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D006801:Humans; D031566:Magnolia / Q000737:chemistry; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010647:Phenyl Ethers / Q000302:isolation & purification / Q000494:pharmacology*; D010766:Phosphorylation; D018515:Plant Leaves; D011837:Radiation-Protective Agents / Q000302:isolation & purification / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D012867:Skin / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D051785:Smad Proteins / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014466:Ultraviolet Rays
chemical_list: D001713:Biphenyl Compounds; D024042:Collagen Type I; D061965:Matrix Metalloproteinase Inhibitors; D010647:Phenyl Ethers; D011837:Radiation-Protective Agents; D051785:Smad Proteins; D018808:Transcription Factor AP-1; D016212:Transforming Growth Factor beta; C036795:obovatol; D020928:Mitogen-Activated Protein Kinases; D019278:Matrix Metalloproteinase 3