Wound-healing effect of ginsenoside Rd from leaves of Panax ginseng via cyclic AMP-dependent protein kinase pathway

Eur J Pharmacol. 2013 Feb 28;702(1-3):285-93. doi: 10.1016/j.ejphar.2013.01.048. Epub 2013 Feb 8.


Panax ginseng is considered as one of the most valuable medicinal herbs in traditional medicine, and ginsenoside Rd is one of the main active ingredients in P. ginseng leaf. Although there is significant number of evidences implicated on the beneficial effects of the ginsenosides with diverse associated mechanisms, reports on the skin regeneration by the ginsenoside Rd are not sufficient. Therefore, we examined the mitogenic and protective effects of the ginsenoside Rd in the keratinocyte progenitor cells (KPCs) and human dermal fibroblasts (HDFs). Furthermore, the signaling pathways involved in the activation of KPCs and HDFs were investigated, and wound-healing effect is evaluated in vivo through animal wound models. We found that the ginsenoside Rd significantly increased the proliferation and migration level of KPCs and HDFs in a dose-dependent manner. Additionally, the cell survival was significantly increased in H2O2 treated KPCs. Moreover, the ginsenoside Rd effectively induced collagen type 1 and down-regulated matrix metalloprotinase-1 (MMP-1) in a dose-dependent manner. All of these beneficial effects are associated with an induction of intracellular cAMP levels and phosphorylated cAMP response element-binding protein expression in nucleus, which both attenuated by adenine 9-β-d-arabinofuranoside, an adenylate cyclase inhibitor. Application of the ginsenoside Rd to an excision wound in mice showed an effective healing process. As skin regeneration is mainly associated with the activation of HDFs and KPCs, P. ginseng leaf, an alternative source of the ginsenoside Rd, can be used as a natural source for skin regeneration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Collagen / metabolism
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Female
  • Fibroblasts / drug effects*
  • Fibroblasts / metabolism
  • Ginsenosides / pharmacology*
  • Ginsenosides / therapeutic use
  • Humans
  • Keratinocytes / cytology
  • Matrix Metalloproteinase 1 / metabolism
  • Mice
  • Mice, Hairless
  • Panax
  • Phytotherapy*
  • Plant Leaves / chemistry
  • Signal Transduction
  • Skin / cytology
  • Stem Cells / drug effects*
  • Stem Cells / metabolism
  • Wound Healing / drug effects*


  • Cyclic AMP Response Element-Binding Protein
  • Ginsenosides
  • Collagen
  • Cyclic AMP-Dependent Protein Kinases
  • MMP1 protein, human
  • Matrix Metalloproteinase 1
  • ginsenoside Rd