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

被引：258

作者：

Chung, Byung-Hee ^{[1
,2
,3
]}

Kim, Jong-Dai ^{[3
]}

Kim, Chun-Ki ^{[1
,2
]}

Kim, Jung Huan ^{[1
,2
]}

Won, Moo-Ho ^{[4
]}

Lee, Han-Soo ^{[1
,2
]}

Dong, Mi-Sook ^{[5
]}

Ha, Kwon-Soo ^{[1
,2
]}

Kwon, Young-Geun ^{[6
]}

Kim, Young-Myeong ^{[1
,2
]}

机构：

[1] Kangwon Natl Univ, Sch Med, Vasc Syst Res Ctr, Chunchon 200701, Kangwon Do, South Korea

[2] Kangwon Natl Univ, Sch Med, Dept Mol & Cellular Biochem, Chunchon 200701, Kangwon Do, South Korea

[3] Kangwon Natl Univ, Sch Biotechnol, Div Food Biotechnol, Chunchon 200701, Kangwon Do, South Korea

[4] Hallym Univ, Sch Med, Dept Anat, Chunchon, Kangwon Do, South Korea

[5] Korea Univ, Sch Life Sci & Biotechnol, Seoul 136701, South Korea

[6] Yonsei Univ, Coll Sci, Dept Biochem, Seoul 120749, South Korea

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2008年 / 376卷 / 02期

关键词：

Icariin; Angiogenesis; Human umbilical vein endothelial cell; Nitric oxide synthase; Signal pathway;

D O I：

10.1016/j.bbrc.2008.09.001

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 [生物化学与分子生物学]; 081704 [应用化学];

摘要：

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. (C) 2008 Published by Elsevier Inc.

引用

页码：404 / 408

页数：5

共 24 条

[1]

Molecular mechanisms of blood vessel formation [J].