Increase of collagen synthesis by obovatol through stimulation of the TGF-beta signaling and inhibition of matrix metalloproteinase in UVB-irradiated human fibroblast.
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.
Choi
Myoung Suk
MS
College of Pharmacy, Chungbuk National University, 48, Gaesin-dong, Heungduk-gu, Cheungju, Chungbuk 361-763, South Korea.
Yoo
Myung Sik
MS
Son
Dong Ju
DJ
Jung
Hai Young
HY
Lee
Seung Ho
SH
Jung
Jae Kyung
JK
Lee
Beom Cheon
BC
Yun
Yeo Pyo
YP
Pyo
Hyeong Bae
HB
Hong
Jin Tae
JT
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
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