title: Cholestin (Monascus purpureus rice) inhibits homocysteine-induced reactive oxygen species generation, nuclear factor-kappaB activation, and vascular cell adhesion molecule-1 expression in human aortic endothelial cells.
abstract: 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.
authors: Institute of Public Health, National Yang-Ming University, No. 155, Sec. 2, Linong St., Peitou, Taipei , 112, Taiwan.
authors: Chih-Pei
authors: CP
authors: Lin
authors: Yung-Hsiang
authors: YH
authors: Chen
authors: Jaw-Wen
authors: JW
authors: Chen
authors: Hsin-Bang
authors: HB
authors: Leu
authors: Tsan-Zon
authors: TZ
authors: Liu
authors: Po-Len
authors: PL
authors: Liu
authors: Song-Lih
authors: SL
authors: Huang
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001011:Aorta; D050197:Atherosclerosis / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D001688:Biological Products / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D053379:Chromogranin A / Q000494:pharmacology; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects*; D006710:Homocysteine / Q000494:pharmacology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D006937:Hypercholesterolemia / Q000150:complications / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012307:Risk Factors; D019821:Simvastatin / Q000494:pharmacology; D020298:U937 Cells; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis*
chemical_list: D000893:Anti-Inflammatory Agents; D001688:Biological Products; D053379:Chromogranin A; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D016328:NF-kappa B; D010446:Peptide Fragments; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D019010:Vascular Cell Adhesion Molecule-1; C082443:parastatin; C117343:red yeast rice; D006710:Homocysteine; D019821:Simvastatin