Astragaloside IV and cycloastragenol stimulate the phosphorylation of extracellular signal-regulated protein kinase in multiple cell types

Planta Med. 2012 Jan;78(2):115-21. doi: 10.1055/s-0031-1280346. Epub 2011 Nov 14.


Two Chinese herb-derived small molecule telomerase activators, astragaloside IV (AG-IV) and cycloastragenol (CAG), have recently been shown to improve the proliferative response of CD8+ T lymphocytes from HIV-infected patients by upregulating telomerase activity. Here, we examined the signaling mechanism of AG-IV and CAG. Telomerase activity in human embryonic kidney HEK293 fibroblasts was increased upon treatment with increasing concentrations of AG-IV or CAG. Both compounds induced the phosphorylation of extracellular signal-regulated protein kinase (ERK) in a time- and dose-dependent manner in HEK293 cells and HEK-neo keratinocytes. AG-IV and CAG also stimulated ERK phosphorylation in other cell lines of lung, brain, mammary, endothelial, and hematopoietic origins. Use of selective inhibitors and dominant negative mutants revealed the involvement of c-Src, MEK (ERK kinase), and epidermal growth factor receptor in CAG-induced ERK phosphorylation. Our data indicate that AG-IV and CAG may exert their cellular effects through the activation of the Src/MEK/ERK pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Astragalus Plant / chemistry*
  • Brain / drug effects
  • Brain / metabolism
  • Breast / drug effects
  • Breast / metabolism
  • Cell Line
  • Dose-Response Relationship, Drug
  • Endothelial Cells / drug effects
  • ErbB Receptors / metabolism
  • Extracellular Signal-Regulated MAP Kinases / metabolism*
  • Fibroblasts / drug effects*
  • Humans
  • Lung / drug effects
  • Lung / metabolism
  • Phosphorylation
  • Plant Extracts / pharmacology*
  • Sapogenins / pharmacology*
  • Saponins / pharmacology*
  • Telomerase / metabolism*
  • Triterpenes / pharmacology*
  • src-Family Kinases / metabolism


  • Plant Extracts
  • Sapogenins
  • Saponins
  • Triterpenes
  • astragaloside A
  • ErbB Receptors
  • src-Family Kinases
  • Extracellular Signal-Regulated MAP Kinases
  • Telomerase
  • cycloastragenol