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

Journal Article · Fri Nov 14 04:00:00 EST 2008 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/j.bbrc.2008.09.001· OSTI ID:21217103

Chung, Byung-Hee ^[1]; Kim, Jong-Dai ^[2]; Kim, Chun-Ki; Kim, Jung Huan ^[1]; Won, Moo-Ho ^[3]; Lee, Han-Soo ^[1]; Dong, Mi-Sook ^[4]; Ha, Kwon-Soo ^[1]; Kwon, Young-Geun ^[5]; Kim, Young-Myeong ^[1]

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1. Vascular System Research Center and Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chunchon, Kangwon-do 200-701 (Korea, Republic of)
2. Division of Food Biotechnology, School of Biotechnology, Kangwon National University, Chunchon, Kangwon-do (Korea, Republic of)
3. Department of Anatomy, School of Medicine, Hallym University, Chunchon, Kangwon-do (Korea, Republic of)
4. School of Life Sciences and Biotechnology, Korea University, 1, 5-Ka, Anam-dong, Sungbuk-ku, Seoul 136-701 (Korea, Republic of)
5. Department of Biochemistry, College of Sciences, Yonsei University, Seoul (Korea, Republic of)

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.

• OSTI ID: 21217103
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 2 Vol. 376; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CELL PROLIFERATION
DRUGS
HUMAN POPULATIONS
IN VITRO
IN VIVO
NITRIC OXIDE
PHOSPHORYLATION
THERAPY
VEINS