Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon, Gangwon-Do, 200-701, Republic of Korea.
Phytother Res. 2013 Nov;27(11):1700-7. doi: 10.1002/ptr.4924. Epub 2013 Jan 8.
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.
血管平滑肌细胞（VSMC）的异常增殖和迁移对动脉粥样硬化和再狭窄的发病机制有重要贡献。在这里，我们研究了从药用植物土木香中分离得到的倍半萜内酯艾蒲萜内酯（EuTL）对血小板衍生生长因子（PDGF）诱导的大鼠主动脉平滑肌细胞（RASMC）增殖和迁移的影响及其潜在机制。EuTL 显著抑制 PDGF 诱导的 RASMC 增殖和迁移。EuTL 处理 RASMC 可诱导血红素加氧酶-1（HO-1）的蛋白和 mRNA 表达。SB203580（p38 抑制剂）、SP600125（JNK 抑制剂）、U0126（MEK 抑制剂）和 LY294002（PI3K 抑制剂）均不能抑制 EuTL 诱导的 HO-1 表达；然而，N-乙酰半胱氨酸（NAC，一种抗氧化剂）阻断了 EuTL 诱导的 HO-1 表达。此外，EuTL 处理 RASMC 可增加活性氧（ROS）的积累和核因子-E2 相关因子 2（Nrf2）的核转位；然而，这种转位也被 NAC 抑制。NAC 或 HO-1 的抑制显著减弱了 EuTL 对 PDGF 诱导的 RASMC 增殖和迁移的抑制作用。综上所述，这些发现表明，EuTL 可通过 ROS-Nrf2 途径诱导 HO-1 抑制 PDGF 诱导的 VSMC 增殖和迁移，可能是预防或治疗血管疾病的潜在 HO-1 诱导剂。
