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; Eunjung Lee; Sang Gwon Seo; Jihoon Lee; Jong Eun Kim; Jiyoung Kim; Ki Won Lee; Hyong Joo Lee

doi:10.1055/s-0033-1350621

Planta Medica, Table of Contents

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

¹WCU Biomodulation Major, Department of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea

,

Eunjung Lee

¹WCU Biomodulation Major, Department of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea

,

Sang Gwon Seo

¹WCU Biomodulation Major, Department of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea

,

Jihoon Lee

¹WCU Biomodulation Major, Department of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea

,

Jong Eun Kim

⁴The Hormel Institute, University of Minnesota, Minnesota, USA

,

Jiyoung Kim

¹WCU Biomodulation Major, Department of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea

²Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea

³Advanced Institutes of Convergence Technology, Seoul National University, Suwon, Republic of Korea

,

Ki Won Lee

¹WCU Biomodulation Major, Department of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea

²Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea

³Advanced Institutes of Convergence Technology, Seoul National University, Suwon, Republic of Korea

,

Hyong Joo Lee

¹WCU Biomodulation Major, Department of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea

²Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea

³Advanced Institutes of Convergence Technology, Seoul National University, Suwon, Republic of Korea

› Author Affiliations

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

Full Text

References

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