Icariin stimulates angiogenesis by activating the MEK/ERK- and PI3K/Akt/eNOS-dependent signal pathways in human endothelial cells |
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Authors: | Chung Byung-Hee Kim Jong-Dai Kim Chun-Ki Kim Jung Hwan Kim Jung Huan Won Moo-Ho Lee Han-Soo Dong Mi-Sook Ha Kwon-Soo Kwon Young-Geun Kim Young-Myeong |
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Affiliation: | a Vascular System Research Center and Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chunchon, Kangwon-do 200-701, Republic of Korea b Division of Food Biotechnology, School of Biotechnology, Kangwon National University, Chunchon, Kangwon-do, Republic of Korea c Department of Anatomy, School of Medicine, Hallym University, Chunchon, Kangwon-do, Republic of Korea d School of Life Sciences and Biotechnology, Korea University, 1, 5-Ka, Anam-dong, Sungbuk-ku, Seoul 136-701, Republic of Korea e Department of Biochemistry, College of Sciences, Yonsei University, Seoul, Republic of Korea |
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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. |
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Keywords: | Icariin Angiogenesis Human umbilical vein endothelial cell Nitric oxide synthase Signal pathway |
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