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Planta Med 2012; 78(2): 115-121
DOI: 10.1055/s-0031-1280346
Biological and Pharmacological Activity
Original Papers
© Georg Thieme Verlag KG Stuttgart · New York

Astragaloside IV and Cycloastragenol Stimulate the Phosphorylation of Extracellular Signal-Regulated Protein Kinase in Multiple Cell Types

Lisa Y. Yung1 , Wing See Lam1 , Maurice K. C. Ho1 , Yueqing Hu1 , Fanny C. F. Ip1 , Haihong Pang1 , Allison C. Chin2 , Calvin B. Harley2 , Nancy Y. Ip1 , 2 , Yung H. Wong1 , 2
  • 1Biotechnology Research Institute and Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China
  • 2TA Therapeutics Limited (a Geron-BRC/HKUST Joint Venture), Hong Kong, China
Further Information

Publication History

received March 18, 2011 revised October 12, 2011

accepted October 16, 2011

Publication Date:
14 November 2011 (online)

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Abstract

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.

Key words

Astragalus membranaceus - Fabaceae - cycloartane triterpenoid saponin - mitogen-activated protein kinase - telomerase activation

Supporting Information

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Prof. Yung Hou Wong

Division of Life Science
The Hong Kong University of Science and Technology

Clear Water Bay, Kowloon

Hong Kong

China

Phone: +85 2 23 58 73 28

Fax: +8 52 23 58 15 52

Email: boyung@ust.hk