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

doi:10.1016/j.bbrc.2008.09.001

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

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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 language	English
Pages (from-to)	404-408
Number of pages	5
Journal	Biochemical and Biophysical Research Communications
Volume	376
Issue number	2
DOIs	https://doi.org/10.1016/j.bbrc.2008.09.001
Publication status	Published - 2008 Nov 14

Bibliographical note

Funding Information:
This work was supported by Vascular System Research Center grant from the Korea Science and Engineering Foundation (Y.M.K), the Korea Food and Drug Administration through the National Center for the Standardization of Herbal Medicine (Y.M.K), and National Research Laboratory grant ROA-2007-000-20099-0 from the Korea Science and Engineering Foundation funded by MoST (Y.G.K).

All Science Journal Classification (ASJC) codes

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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10.1016/j.bbrc.2008.09.001

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Chung, B. H., Kim, J. D., Kim, C. K., Kim, J. W., Won, M. H., Lee, H. S., Dong, M. S., Ha, K. S., Kwon, Y. G., & Kim, Y. M. (2008). Icariin stimulates angiogenesis by activating the MEK/ERK- and PI3K/Akt/eNOS-dependent signal pathways in human endothelial cells. Biochemical and Biophysical Research Communications, 376(2), 404-408. https://doi.org/10.1016/j.bbrc.2008.09.001

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

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.",

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

note = "Funding Information: This work was supported by Vascular System Research Center grant from the Korea Science and Engineering Foundation (Y.M.K), the Korea Food and Drug Administration through the National Center for the Standardization of Herbal Medicine (Y.M.K), and National Research Laboratory grant ROA-2007-000-20099-0 from the Korea Science and Engineering Foundation funded by MoST (Y.G.K). ",

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doi = "10.1016/j.bbrc.2008.09.001",

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AU - Kim, Chun Ki

AU - Kim, Jung Whan

AU - Won, Moo Ho

AU - Lee, Han Soo

AU - Dong, Mi Sook

AU - Ha, Kwon Soo

AU - Kwon, Young Geun

AU - Kim, Young Myeong

N1 - Funding Information: This work was supported by Vascular System Research Center grant from the Korea Science and Engineering Foundation (Y.M.K), the Korea Food and Drug Administration through the National Center for the Standardization of Herbal Medicine (Y.M.K), and National Research Laboratory grant ROA-2007-000-20099-0 from the Korea Science and Engineering Foundation funded by MoST (Y.G.K).

PY - 2008/11/14

Y1 - 2008/11/14

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.

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

Abstract

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