Water extract of Korean red ginseng stimulates angiogenesis by activating the PI3K/Akt-dependent ERK1/2 and eNOS pathways in human umbilical vein endothelial cells

Young Mi Kim, Seung Namkoong, Young Gab Yun, Hee Do Hong, Young Chul Lee, Kwon Soo Ha, Hansoo Lee, Ho Jeong Kwon, Young-Guen Kwon, Young Myeong Kim

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Abstract

Angiogenesis is important for promoting cardiovascular disease, wound healing, and tissue regeneration. We investigated the effects of Korean red ginseng water extract (KRGE) on angiogenesis and its underlying signal mechanism. KRGE increased in vitro proliferation, migration, and tube formation of human umbilical vein endothelial cells, as well as stimulated in vivo angiogenesis without increasing VEGF expression. KRGE-induced angiogenesis was accompanied by phosphorylation of ERK1/2, phosphatidylinositol 3-kinase (Akt), and endothelial nitric oxide synthase (eNOS) as well as an increase in NO production. Inhibition of PI3K activity by wortmannin completely inhibited KRGE-induced angiogenesis and phosphorylation of Akt, ERK1/2, and eNOS, indicating that PI3K/Akt activation is an upstream event of the KRGE-mediated angiogenic pathway. The MEK inhibitor PD98059 blocked KRGE-induced ERK1/2 phosphorylation without affecting Akt and eNOS activation. However, the eNOS inhibitor NG-monomethyl-L-arginine effectively inhibited tube formation, but partially blocked proliferation and migration as well as ERK phosphorylation, without altering Akt and eNOS activation, revealing that the eNOS/NO pathway is partially involved in ERK1/2 activation. This study demonstrated that KRGE stimulates in vitro and in vivo angiogenesis through the activation of the PI3K/Akt-dependent ERK1/2 and eNOS signal pathways and their cross talk.

Original languageEnglish
Pages (from-to)1674-1679
Number of pages6
JournalBiological and Pharmaceutical Bulletin
Volume30
Issue number9
DOIs
Publication statusPublished - 2007 Sep 1

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Panax
Nitric Oxide Synthase Type III
Human Umbilical Vein Endothelial Cells
Phosphatidylinositol 3-Kinases
Water
Phosphorylation
Phosphatidylinositol 3-Kinase
omega-N-Methylarginine
Mitogen-Activated Protein Kinase Kinases
Wound Healing
Vascular Endothelial Growth Factor A
Regeneration
Signal Transduction
Cardiovascular Diseases

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science

Cite this

Kim, Young Mi ; Namkoong, Seung ; Yun, Young Gab ; Hong, Hee Do ; Lee, Young Chul ; Ha, Kwon Soo ; Lee, Hansoo ; Kwon, Ho Jeong ; Kwon, Young-Guen ; Kim, Young Myeong. / Water extract of Korean red ginseng stimulates angiogenesis by activating the PI3K/Akt-dependent ERK1/2 and eNOS pathways in human umbilical vein endothelial cells. In: Biological and Pharmaceutical Bulletin. 2007 ; Vol. 30, No. 9. pp. 1674-1679.
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Water extract of Korean red ginseng stimulates angiogenesis by activating the PI3K/Akt-dependent ERK1/2 and eNOS pathways in human umbilical vein endothelial cells. / Kim, Young Mi; Namkoong, Seung; Yun, Young Gab; Hong, Hee Do; Lee, Young Chul; Ha, Kwon Soo; Lee, Hansoo; Kwon, Ho Jeong; Kwon, Young-Guen; Kim, Young Myeong.

In: Biological and Pharmaceutical Bulletin, Vol. 30, No. 9, 01.09.2007, p. 1674-1679.

Research output: Contribution to journalArticle

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AU - Kim, Young Mi

AU - Namkoong, Seung

AU - Yun, Young Gab

AU - Hong, Hee Do

AU - Lee, Young Chul

AU - Ha, Kwon Soo

AU - Lee, Hansoo

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AU - Kwon, Young-Guen

AU - Kim, Young Myeong

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N2 - Angiogenesis is important for promoting cardiovascular disease, wound healing, and tissue regeneration. We investigated the effects of Korean red ginseng water extract (KRGE) on angiogenesis and its underlying signal mechanism. KRGE increased in vitro proliferation, migration, and tube formation of human umbilical vein endothelial cells, as well as stimulated in vivo angiogenesis without increasing VEGF expression. KRGE-induced angiogenesis was accompanied by phosphorylation of ERK1/2, phosphatidylinositol 3-kinase (Akt), and endothelial nitric oxide synthase (eNOS) as well as an increase in NO production. Inhibition of PI3K activity by wortmannin completely inhibited KRGE-induced angiogenesis and phosphorylation of Akt, ERK1/2, and eNOS, indicating that PI3K/Akt activation is an upstream event of the KRGE-mediated angiogenic pathway. The MEK inhibitor PD98059 blocked KRGE-induced ERK1/2 phosphorylation without affecting Akt and eNOS activation. However, the eNOS inhibitor NG-monomethyl-L-arginine effectively inhibited tube formation, but partially blocked proliferation and migration as well as ERK phosphorylation, without altering Akt and eNOS activation, revealing that the eNOS/NO pathway is partially involved in ERK1/2 activation. This study demonstrated that KRGE stimulates in vitro and in vivo angiogenesis through the activation of the PI3K/Akt-dependent ERK1/2 and eNOS signal pathways and their cross talk.

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