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Planta Med 2013; 79(12): 1009-1016
DOI: 10.1055/s-0033-1350621
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Eupatilin, a Major Flavonoid of Artemisia, Attenuates Aortic Smooth Muscle Cell Proliferation and Migration by Inhibiting PI3K, MKK3/6, and MKK4 Activities

Joe Eun Son
1   WCU Biomodulation Major, Department of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea
,
Eunjung Lee
1   WCU Biomodulation Major, Department of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea
,
Sang Gwon Seo
1   WCU Biomodulation Major, Department of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea
,
Jihoon Lee
1   WCU Biomodulation Major, Department of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea
,
Jong Eun Kim
4   The Hormel Institute, University of Minnesota, Minnesota, USA
,
Jiyoung Kim
1   WCU Biomodulation Major, Department of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea
2   Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea
3   Advanced Institutes of Convergence Technology, Seoul National University, Suwon, Republic of Korea
,
Ki Won Lee
1   WCU Biomodulation Major, Department of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea
2   Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea
3   Advanced Institutes of Convergence Technology, Seoul National University, Suwon, Republic of Korea
,
Hyong Joo Lee
1   WCU Biomodulation Major, Department of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea
2   Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea
3   Advanced Institutes of Convergence Technology, Seoul National University, Suwon, Republic of Korea
› Author Affiliations
Further Information

Publication History

received 24 March 2013
revised 19 June 2013

accepted 20 June 2013

Publication Date:
22 July 2013 (online)

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Abstract

Eupatilin, a major flavonoid of plants in the genus Artemisia, has been shown to exhibit anti-inflammatory, anti-oxidative, and anti-tumor effects. However, the potential anti-atherogenic effects of eupatilin and any underlying mechanisms have not been investigated. In the present study, we sought to determine the effects of eupatilin on phenotypes induced by the growth factor PDGF-BB in human aortic smooth muscle cells. Here we show that aortic sprouting as well as PDGF-BB-induced proliferation and migration of human aortic smooth muscle cells were significantly inhibited by eupatilin. We found that eupatilin inhibited PI3K activity, causing a direct effect on phosphorylation of the downstream kinases Akt and p70S6K. In parallel, eupatilin also inhibited the phosphorylation of MKK3/6-p38 MAPK and the MKK4-JNK pathway. Moreover we found that eupatilin exhibited stronger inhibition effects on PDGF-BB-induced proliferation and migration of human aortic smooth muscle cells than PI3K, p38 MAPK, and JNK pathway inhibitors. Taken together, our results indicate that eupatilin is a potent anti-atherogenic agent that inhibits PDGF-BB-induced proliferation and migration in HASMCs as well as aortic sprouting, which is likely mediated through the attenuation of PI3K, MKK3/6, and MKK4 activation.

Key words

eupatilin - aortic smooth muscle cells - platelet-derived growth factor - PI3K - MAPKs - atherosclerosis

Supporting Information

 

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