The effect of 4-hydroxypanduratin A on the mitogen-activated protein kinase-dependent activation of matrix metalloproteinase-1 expression in human skin fibroblasts.
BACKGROUND
Exposure of ultraviolet (UV) light on the skin induces photoaging associated with up-regulated matrix metalloproteinases (MMPs) activities. The MMP-1 expression due to UV irradiation can be mediated by mitogen-activated protein kinases (MAPKs) such as extracellular signal-regulated kinase (ERK), Jun-N-terminal kinase (JNK) and p38 kinase activation.


OBJECTIVE
We investigated the effects of 4-hydroxypanduratin A, isolated from Kaempferia pandurata Roxb., on the expression of MMP-1 and activation of MAPKs signal pathways in UV-irradiated human skin fibroblasts.


METHODS
The fibroblasts were treated with 4-hydroxypanduratin A for indicated times and the cells were irradiated with UVB. MMP-1 protein expression and phosphorylation of MAPKs were determined by Western blot. Activator protein-1 (AP-1) DNA binding activity was investigated using electrophoretic mobility shift assay (EMSA).


RESULTS
4-Hydroxypanduratin A in the range of 0.001-0.1microM significantly reduced the expression of MMP-1 levels and inhibited UV-induced MAPKs activation. Moreover, inhibition of MAPKs by 4-hydroxypanduratin A resulted in decreasing c-Fos expression and c-Jun phosphorylation induced by UV, which led to inhibiting AP-1 DNA binding activity.


CONCLUSIONS
The results suggest that 4-hydroxypanduratin A can be a potential candidate for the prevention and treatment of skin aging brought about by UV.
Shim
Jae-Seok
JS
Department of Biomaterials Science and Engineering, Yonsei University, Seoul, Republic of Korea.
Han
Young-Sun
YS
Hwang
Jae-Kwan
JK
D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D047188:Chalcones / Q000494:pharmacology*; D003879:Dermatologic Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D005347:Fibroblasts / Q000187:drug effects* / Q000201:enzymology / Q000528:radiation effects; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D012867:Skin / Q000187:drug effects* / Q000201:enzymology / Q000528:radiation effects; D015595:Skin Aging / Q000187:drug effects*; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014466:Ultraviolet Rays
C525185:4-hydroxypanduratin A; D047188:Chalcones; D003879:Dermatologic Agents; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; D020928:Mitogen-Activated Protein Kinases; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1