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Eupatolide Inhibits PDGF‐induced Proliferation and Migration of Aortic Smooth Muscle Cells Through ROS‐dependent Heme Oxygenase‐1 Induction
Author(s) -
Kim Namho,
Hwangbo Cheol,
Lee Suhyun,
Lee JeongHyung
Publication year - 2013
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.4924
Subject(s) - heme oxygenase , vascular smooth muscle , ly294002 , microbiology and biotechnology , platelet derived growth factor receptor , biology , heme , growth factor , p38 mitogen activated protein kinases , pi3k/akt/mtor pathway , cell growth , platelet derived growth factor , mapk/erk pathway , signal transduction , biochemistry , endocrinology , receptor , smooth muscle , enzyme
The abnormal proliferation and migration of vascular smooth muscle cell (VSMC) contributes importantly to the pathogenesis of atherosclerosis and restenosis. Here, we investigated the effects of eupatolide (EuTL), a sesquiterpene lactone isolated from the medicinal plant Inula britannica , on platelet‐derived growth factor (PDGF)‐induced proliferation and migration of primary rat aortic smooth muscle cells (RASMCs), as well as its underlying mechanisms. EuTL remarkably inhibited PDGF‐induced proliferation and migration of RASMCs. Treatment of RASMCs with EuTL induced both protein and mRNA expression of heme oxygenase‐1 (HO‐1). SB203580 (a p38 inhibitor), SP600125 (a JNK inhibitor), U0126 (a MEK inhibitor) and LY294002 (a PI3K inhibitor) did not suppress EuTL‐induced HO‐1 expression; however, N‐acetylcysteine (NAC, an antioxidant) blocked EuTL‐induced HO‐1 expression. Moreover, treatment of RASMCs with EuTL increased reactive oxygen species (ROS) accumulation and nuclear translocation of nuclear factor‐E2‐related factor 2 (Nrf2); however, this translocation was also inhibited by NAC. NAC or inhibition of HO‐1 significantly attenuated the inhibitory effects of EuTL on PDGF‐induced proliferation and migration of RASMCs. Taken together, these findings suggest that EuTL could suppress PDGF‐induced proliferation and migration of VSMCs through HO‐1 induction via ROS‐Nrf2 pathway and may be a potential HO‐1 inducer for preventing or treating vascular diseases. Copyright © 2013 John Wiley & Sons, Ltd.