title: Nobiletin inhibits oxidized-LDL mediated expression of Tissue Factor in human endothelial cells through inhibition of NF-κB.
abstract: BACKGROUND
  Flavonoids are nutrients usually included in human diet with several significant biological activities. Nobiletin is a flavonoid that, besides having anti-inflammatory and anti-tumoral activity, seems to exert protective effects on cardiovascular system. Several studies investigated nobiletin as a natural drug to antagonize the atherosclerotic disease. On the contrary, literature about its potential role in modulating the main acute complication of atherosclerosis, thrombosis, is still scanty. Several studies have indicated that Tissue Factor (TF) plays a pivotal role in the pathophysiology of cardiovascular thrombotic events by triggering the formation of intracoronary thrombi. Oxidized-LDL have an important role in promoting athero-thrombotic events. This study investigates whether nobiletin might exert protective cardiovascular effects by preventing the oxidized-LDL mediated expression of TF in human endothelial cells in vitro. Moreover, we have studied whether the nobiletin effects might be modulated by the inhibition of the NF-κB pathway.
  
  
  RESULTS
  In HUVEC, ox-LDL induced TF-mRNA transcription as demonstrated by real time PCR and expression of functionally active TF as demonstrated by Western-blot, FACS analysis and pro-coagulant activity assay. Nobiletin prevented these ox-LDL-mediated effects by exerting antioxidant effects, finally leading to inhibition of the transcription factor NF-κB.
  
  
  CONCLUSIONS
  These data suggest that nobiletin might be a potential antithrombotic agent of dietary origin. This flavonoid, through its antioxidant proprieties, might potentially exert an antithrombotic activity by inhibiting TF expression/activity in a cell population never investigated before in this context and that is normally represented in vessel wall such as endothelial cells.
authors.affiliation: Department of Advanced Biomedical Sciences, Division of Cardiology, University of Naples, "Federico II", Naples, Italy. Electronic address: pcirillo@unina.it.
authors.forename: Plinio
authors.initials: P
authors.lastname: Cirillo
authors.affiliation: Department of Cardiothoracic and Respiratory Sciences, Division of Cardiology, Second University of Naples, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Conte
authors.affiliation: Department of Cardiothoracic and Respiratory Sciences, Division of Cardiology, Second University of Naples, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Cimmino
authors.affiliation: Department of Advanced Biomedical Sciences, Division of Cardiology, University of Naples, "Federico II", Naples, Italy.
authors.forename: Grazia
authors.initials: G
authors.lastname: Pellegrino
authors.affiliation: Department of Advanced Biomedical Sciences, Division of Cardiology, University of Naples, "Federico II", Naples, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Ziviello
authors.affiliation: Department of Internal and Experimental Medicine, Second University of Naples, Italy.
authors.forename: Giusi
authors.initials: G
authors.lastname: Barra
authors.affiliation: Department of Internal and Experimental Medicine, Second University of Naples, Italy.
authors.forename: Ferdinando Carlo
authors.initials: FC
authors.lastname: Sasso
authors.affiliation: Department of Advanced Biomedical Sciences, Division of Cardiology, University of Naples, "Federico II", Naples, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Borgia
authors.affiliation: Department of Internal and Experimental Medicine, Second University of Naples, Italy; IBP-CNR, Naples, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: De Palma
authors.affiliation: Department of Advanced Biomedical Sciences, Division of Cardiology, University of Naples, "Federico II", Naples, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Trimarco
mesh_terms: D002317:Cardiovascular Agents / Q000494:pharmacology*; D047309:Flavones / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000378:metabolism; D013925:Thromboplastin / Q000235:genetics / Q000378:metabolism*
chemical_list: D002317:Cardiovascular Agents; D047309:Flavones; D008077:Lipoproteins, LDL; D016328:NF-kappa B; D012333:RNA, Messenger; C099252:oxidized low density lipoprotein; D013925:Thromboplastin; C008661:nobiletin
keywords: Flavonoids; Nobiletin; Thrombosis; Tissue Factor