Increase of collagen synthesis by obovatol through stimulation of the TGF-beta signaling and inhibition of matrix metalloproteinase in UVB-irradiated human fibroblast

J Dermatol Sci. 2007 May;46(2):127-37. doi: 10.1016/j.jdermsci.2007.02.001. Epub 2007 Mar 7.

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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biphenyl Compounds / isolation & purification
  • Biphenyl Compounds / pharmacology*
  • Cells, Cultured
  • Collagen Type I / biosynthesis*
  • Dose-Response Relationship, Drug
  • Dose-Response Relationship, Radiation
  • Fibroblasts / drug effects*
  • Fibroblasts / metabolism
  • Fibroblasts / radiation effects
  • Humans
  • Magnolia / chemistry
  • Matrix Metalloproteinase 3 / metabolism
  • Matrix Metalloproteinase Inhibitors*
  • Mitogen-Activated Protein Kinases / metabolism
  • Phenyl Ethers / isolation & purification
  • Phenyl Ethers / pharmacology*
  • Phosphorylation
  • Plant Leaves
  • Radiation-Protective Agents / isolation & purification
  • Radiation-Protective Agents / pharmacology*
  • Signal Transduction / drug effects*
  • Skin / drug effects
  • Skin / metabolism
  • Skin / radiation effects
  • Smad Proteins / metabolism
  • Transcription Factor AP-1 / metabolism
  • Transforming Growth Factor beta / metabolism*
  • Ultraviolet Rays*

Substances

  • Biphenyl Compounds
  • Collagen Type I
  • Matrix Metalloproteinase Inhibitors
  • Phenyl Ethers
  • Radiation-Protective Agents
  • Smad Proteins
  • Transcription Factor AP-1
  • Transforming Growth Factor beta
  • obovatol
  • Mitogen-Activated Protein Kinases
  • Matrix Metalloproteinase 3