Yang Haitao, Yan Lijie, Qian Peng, Duan Hongyan, Wu Jintao, Li Bing, Wang Shanling
Department of Cardiology, Henan Provincial People's Hospital, Zhengzhou, 450003, China.
J Cell Biochem. 2015 Apr;116(4):580-8. doi: 10.1002/jcb.25009.
Icariin is an important pharmacologically active flavonol diglycoside that can inhibit inflammation in lipopolysaccharide (LPS)-stimulated macrophages. However, little is known about the molecular mechanisms underlying the inhibitory effect of Icariin in the formation of foam cells. In this study, macrophages were cultured with LPS and oxidized low-density lipoprotein (oxLDL) in the presence or absence of Icariin. RT-PCR and western blot were used to detect the levels of mRNA and protein expression of CD36, scavenger receptor class B type I (SR-BI) and the phosphorylation of p38MAPK. It was demonstrated that 4 µM or 20 µM Icariin treatment significantly inhibited the cholesterol ester (CE)/total cholesterol (TC) and oxLDL-mediated foam cell formation (P < 0.05). The binding of oxLDL to LPS-activated macrophages was also significantly hindered by Icariin (P < 0.05). Furthermore, Icariin down-regulated the expression of CD36 in LPS-activated macrophages in a dose-dependent manner and CD36 over-expression restored the inhibitory effect of Icariin on foam cell formation. The phosphorylation of p38MAPK was reduced by Icariin, indicating that Icariin reduced the expression of CD36 through the p38MAPK pathway. In addition, Icariin up-regulated SR-BI protein expression in a dose-dependent manner, and SR-BI gene silencing restored the inhibitory effect of Icariin on foam cell formation. These data demonstrate that Icariin inhibited foam cell formation by down-regulating the expression of CD36 and up-regulating the expression of SR-BI. Therefore, our findings provide a new explanation as to why Icariin could inhibit atherosclerosis.
淫羊藿苷是一种重要的具有药理活性的黄酮醇二糖苷，能够抑制脂多糖（LPS）刺激的巨噬细胞中的炎症反应。然而，关于淫羊藿苷抑制泡沫细胞形成的分子机制知之甚少。在本研究中，在有或没有淫羊藿苷存在的情况下，用LPS和氧化低密度脂蛋白（oxLDL）培养巨噬细胞。采用逆转录聚合酶链反应（RT-PCR）和蛋白质免疫印迹法检测CD36、I类清道夫受体（SR-BI）的mRNA和蛋白表达水平以及p38丝裂原活化蛋白激酶（p38MAPK）的磷酸化水平。结果表明，4 μM或20 μM淫羊藿苷处理可显著抑制胆固醇酯（CE）/总胆固醇（TC）以及oxLDL介导的泡沫细胞形成（P<0.05）。淫羊藿苷也显著阻碍了oxLDL与LPS激活的巨噬细胞的结合（P<0.05）。此外，淫羊藿苷以剂量依赖的方式下调LPS激活的巨噬细胞中CD36的表达，并且CD36过表达恢复了淫羊藿苷对泡沫细胞形成的抑制作用。淫羊藿苷降低了p38MAPK的磷酸化水平，表明淫羊藿苷通过p38MAPK途径降低了CD36的表达。此外，淫羊藿苷以剂量依赖的方式上调SR-BI蛋白表达，并且SR-BI基因沉默恢复了淫羊藿苷对泡沫细胞形成的抑制作用。这些数据表明，淫羊藿苷通过下调CD36的表达和上调SR-BI的表达来抑制泡沫细胞形成。因此，我们的研究结果为淫羊藿苷为何能够抑制动脉粥样硬化提供了新的解释。
