Lin Chih-Pei, Chen Yung-Hsiang, Chen Jaw-Wen, Leu Hsin-Bang, Liu Tsan-Zon, Liu Po-Len, Huang Song-Lih
Institute of Public Health, National Yang-Ming University, No. 155, Sec. 2, Linong St., Peitou, Taipei , 112, Taiwan.
J Biomed Sci. 2008 Mar;15(2):183-96. doi: 10.1007/s11373-007-9212-0. Epub 2007 Sep 30.
Hyperhomocysteinemia is associated with dysfunction and an independent risk factor of cardiovascular diseases. Cholestin (Monascus purpureus-fermented rice), contains a naturally-occurring statin, which has lipid-modulating and anti-inflammatory effects. We investigated the effects of Cholestin extract on the expression of vascular cell adhesion molecule-1 (VCAM-1) by homocysteine (HCY)-treated human aortic endothelial cells (HAECs). Supplement of HAECs with Cholestin extract significantly suppressed cellular binding between the human monocytic cells U937 and HCY-stimulated HAECs. Quantitative PCR and immunoblot analysis showed that Cholestin extract significantly attenuated HCY-induced expression of VCAM-1 mRNA and protein, respectively. Gel shift assays showed that Cholestin treatment reduced HCY-activated transcription factor nuclear factor-kappaB (NF-kappaB). Furthermore, Cholestin also attenuated reactive oxygen species (ROS) generation in vitro and in HCY-treated HAECs. Supplement with statins including simvastatin and parastatin gave similar results as compared with Cholestin. In conclusion, Cholestin reduces HCY-stimulated endothelial adhesiveness as well as downregulating intracellular ROS formation, NF-kappaB activation, and VCAM-1 expression in HAECs, supporting the notion that the natural compound Cholestin may have potential implications in clinical atherosclerosis disease.
高同型半胱氨酸血症与功能障碍相关,是心血管疾病的独立危险因素。红曲米(紫红曲霉发酵大米)含有一种天然存在的他汀类药物,具有调节血脂和抗炎作用。我们研究了红曲米提取物对同型半胱氨酸(HCY)处理的人主动脉内皮细胞(HAECs)中血管细胞黏附分子-1(VCAM-1)表达的影响。用红曲米提取物处理HAECs可显著抑制人单核细胞U937与HCY刺激的HAECs之间的细胞结合。定量PCR和免疫印迹分析表明,红曲米提取物分别显著减弱了HCY诱导的VCAM-1 mRNA和蛋白的表达。凝胶迁移试验表明,红曲米处理降低了HCY激活的转录因子核因子-κB(NF-κB)。此外,红曲米在体外和HCY处理的HAECs中也减弱了活性氧(ROS)的生成。与红曲米相比,补充包括辛伐他汀和帕伐他汀在内的他汀类药物也得到了类似的结果。总之,红曲米降低了HCY刺激的内皮黏附性,并下调了HAECs中细胞内ROS的形成、NF-κB的激活和VCAM-1的表达,支持了天然化合物红曲米可能对临床动脉粥样硬化疾病有潜在影响的观点。