Cardiac Surgical Intensive Care Unit, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing 100029, China.
Pharmacology and Toxicology Research Center, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100094, China.
Molecules. 2014 Jun 6;19(6):7516-27. doi: 10.3390/molecules19067516.
Foam cells formation as a result of the uncontrolled cytophagy of modified cholesterol by macrophages plays a key role in the occurrence and development of atherosclerosis. Sesamin is an active constituent of Sesamum indicum which has been shown to possess multiple pharmacological activities. In this work, we investigated the effects of sesamin on foam cell formation and cholesterol efflux in RAW264.7 macrophages. Sesamin dose-dependently inhibited the enhanced cholesterol accumulation elicited by oxidized low-density lipoprotein cholesterol (oxLDL) in RAW264.7 cells. Treatment with sesamin (10 μM) significantly enhanced cholesterol efflux mediated by high-density lipoprotein (HDL). Realtime quantitative PCR and luciferase assays showed that sesamin significantly increased the mRNA levels of PPARγ, LXRα, and ABCG1, and increased the transcriptional activity of PPARγ. The stimulating effect of sesamin on cholesterol efflux was substantially inhibited by the co-treatment with GW9662, a potent inhibitor of PPARγ. These results suggest that sesamin is a new inhibitor of foam cell formation that may stimulate cholesterol efflux through upregulation of the PPARγ-LXRα-ABCG1 pathway.
泡沫细胞的形成是由于巨噬细胞对修饰胆固醇的失控胞噬作用所致，在动脉粥样硬化的发生和发展中起着关键作用。芝麻素是芝麻中的一种活性成分，已被证明具有多种药理活性。在这项工作中，我们研究了芝麻素对 RAW264.7 巨噬细胞中泡沫细胞形成和胆固醇外排的影响。芝麻素呈剂量依赖性地抑制氧化型低密度脂蛋白胆固醇（oxLDL）诱导的 RAW264.7 细胞中胆固醇蓄积的增强。用芝麻素（10 μM）处理可显著增强由高密度脂蛋白（HDL）介导的胆固醇外排。实时定量 PCR 和荧光素酶检测显示，芝麻素显著增加了 PPARγ、LXRα 和 ABCG1 的 mRNA 水平，并增加了 PPARγ 的转录活性。用 PPARγ 的强效抑制剂 GW9662 共同处理可显著抑制芝麻素对胆固醇外排的刺激作用。这些结果表明，芝麻素是一种新的泡沫细胞形成抑制剂，可通过上调 PPARγ-LXRα-ABCG1 通路刺激胆固醇外排。
