Icariin stimulates angiogenesis by activating the MEK/ERK- and PI3K/Akt/eNOS-dependent signal pathways in human endothelial cells

Byung Hee Chung, Jong Dai Kim, Chun Ki Kim, Jung Whan Kim, Moo Ho Won, Han Soo Lee, Mi Sook Dong, Kwon Soo Ha, Young Geun Kwon, Young Myeong Kim

Research output: Contribution to journalArticle

126 Citations (Scopus)

Abstract

We investigated the molecular effect and signal pathway of icariin, a major flavonoid of Epimedium koreanum Nakai, on angiogenesis. Icariin stimulated in vitro endothelial cell proliferation, migration, and tubulogenesis, which are typical phenomena of angiogenesis, as well as increased in vivo angiogenesis. Icariin activated the angiogenic signal modulators, ERK, phosphatidylinositol 3-kinase (PI3K), Akt, and endothelial nitric oxide synthase (eNOS), and increased NO production, without affecting VEGF expression, indicating that icariin may directly stimulate angiogenesis. Icariin-induced ERK activation and angiogenic events were significantly inhibited by the MEK inhibitor PD98059, without affecting Akt and eNOS phosphorylation. The PI3K inhibitor Wortmannin suppressed icariin-mediated angiogenesis and Akt and eNOS activation without affecting ERK phosphorylation. Moreover, the NOS inhibitor NMA partially reduced the angiogenic activity of icariin. These results suggest that icariin stimulated angiogenesis by activating the MEK/ERK- and PI3K/Akt/eNOS-dependent signal pathways and may be a useful drug for angiogenic therapy.

Original languageEnglish
Pages (from-to)404-408
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume376
Issue number2
DOIs
Publication statusPublished - 2008 Nov 14

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Phosphatidylinositol 3-Kinase
Nitric Oxide Synthase Type III
Mitogen-Activated Protein Kinase Kinases
Endothelial cells
Signal Transduction
Endothelial Cells
Phosphorylation
Epimedium
Chemical activation
icariin
Cell proliferation
Flavonoids
Modulators
Vascular Endothelial Growth Factor A
Cell Movement
Cell Proliferation
Drug Therapy

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Chung, Byung Hee ; Kim, Jong Dai ; Kim, Chun Ki ; Kim, Jung Whan ; Won, Moo Ho ; Lee, Han Soo ; Dong, Mi Sook ; Ha, Kwon Soo ; Kwon, Young Geun ; Kim, Young Myeong. / Icariin stimulates angiogenesis by activating the MEK/ERK- and PI3K/Akt/eNOS-dependent signal pathways in human endothelial cells. In: Biochemical and Biophysical Research Communications. 2008 ; Vol. 376, No. 2. pp. 404-408.
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Icariin stimulates angiogenesis by activating the MEK/ERK- and PI3K/Akt/eNOS-dependent signal pathways in human endothelial cells. / Chung, Byung Hee; Kim, Jong Dai; Kim, Chun Ki; Kim, Jung Whan; Won, Moo Ho; Lee, Han Soo; Dong, Mi Sook; Ha, Kwon Soo; Kwon, Young Geun; Kim, Young Myeong.

In: Biochemical and Biophysical Research Communications, Vol. 376, No. 2, 14.11.2008, p. 404-408.

Research output: Contribution to journalArticle

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AU - Won, Moo Ho

AU - Lee, Han Soo

AU - Dong, Mi Sook

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AU - Kwon, Young Geun

AU - Kim, Young Myeong

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N2 - We investigated the molecular effect and signal pathway of icariin, a major flavonoid of Epimedium koreanum Nakai, on angiogenesis. Icariin stimulated in vitro endothelial cell proliferation, migration, and tubulogenesis, which are typical phenomena of angiogenesis, as well as increased in vivo angiogenesis. Icariin activated the angiogenic signal modulators, ERK, phosphatidylinositol 3-kinase (PI3K), Akt, and endothelial nitric oxide synthase (eNOS), and increased NO production, without affecting VEGF expression, indicating that icariin may directly stimulate angiogenesis. Icariin-induced ERK activation and angiogenic events were significantly inhibited by the MEK inhibitor PD98059, without affecting Akt and eNOS phosphorylation. The PI3K inhibitor Wortmannin suppressed icariin-mediated angiogenesis and Akt and eNOS activation without affecting ERK phosphorylation. Moreover, the NOS inhibitor NMA partially reduced the angiogenic activity of icariin. These results suggest that icariin stimulated angiogenesis by activating the MEK/ERK- and PI3K/Akt/eNOS-dependent signal pathways and may be a useful drug for angiogenic therapy.

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