title: Eupatilin, a major flavonoid of Artemisia, attenuates aortic smooth muscle cell proliferation and migration by inhibiting PI3K, MKK3/6, and MKK4 activities.
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.
authors.affiliation: WCU Biomodulation Major, Department of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea.
authors.forename: Joe Eun
authors.initials: JE
authors.lastname: Son
authors.forename: Eunjung
authors.initials: E
authors.lastname: Lee
authors.forename: Sang Gwon
authors.initials: SG
authors.lastname: Seo
authors.forename: Jihoon
authors.initials: J
authors.lastname: Lee
authors.forename: Jong Eun
authors.initials: JE
authors.lastname: Kim
authors.forename: Jiyoung
authors.initials: J
authors.lastname: Kim
authors.forename: Ki Won
authors.initials: KW
authors.lastname: Lee
authors.forename: Hyong Joo
authors.initials: HJ
authors.lastname: Lee
mesh_terms: D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D019306:Artemisia / Q000737:chemistry*; D000077214:Becaplermin; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005419:Flavonoids / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases; D010766:Phosphorylation / Q000187:drug effects; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000077214:Becaplermin; D005419:Flavonoids; D020928:Mitogen-Activated Protein Kinases; D019869:Phosphatidylinositol 3-Kinases; D010982:Platelet-Derived Growth Factor; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D020574:Proto-Oncogene Proteins c-sis; C045325:eupatilin; C041477:3-hydroxyflavone