The effect of 4-hydroxypanduratin A on the mitogen-activated protein kinase-dependent activation of matrix metalloproteinase-1 expression in human skin fibroblasts

J Dermatol Sci. 2009 Feb;53(2):129-34. doi: 10.1016/j.jdermsci.2008.09.002. Epub 2008 Dec 2.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Survival / drug effects
  • Cells, Cultured
  • Chalcones / pharmacology*
  • Dermatologic Agents / pharmacology*
  • Dose-Response Relationship, Drug
  • Enzyme Activation
  • Fibroblasts / drug effects*
  • Fibroblasts / enzymology
  • Fibroblasts / radiation effects
  • Humans
  • Matrix Metalloproteinase 1 / metabolism*
  • Mitogen-Activated Protein Kinases / metabolism*
  • Phosphorylation
  • Proto-Oncogene Proteins c-fos / metabolism
  • Proto-Oncogene Proteins c-jun / metabolism
  • Signal Transduction / drug effects
  • Skin / drug effects*
  • Skin / enzymology
  • Skin / radiation effects
  • Skin Aging / drug effects*
  • Time Factors
  • Transcription Factor AP-1 / metabolism
  • Ultraviolet Rays

Substances

  • 4-hydroxypanduratin A
  • Chalcones
  • Dermatologic Agents
  • Proto-Oncogene Proteins c-fos
  • Proto-Oncogene Proteins c-jun
  • Transcription Factor AP-1
  • Mitogen-Activated Protein Kinases
  • MMP1 protein, human
  • Matrix Metalloproteinase 1