Cirillo Plinio, Conte Stefano, Cimmino Giovanni, Pellegrino Grazia, Ziviello Francesca, Barra Giusi, Sasso Ferdinando Carlo, Borgia Francesco, De Palma Raffaele, Trimarco Bruno
Department of Advanced Biomedical Sciences, Division of Cardiology, University of Naples, "Federico II", Naples, Italy.
Department of Cardiothoracic and Respiratory Sciences, Division of Cardiology, Second University of Naples, Italy.
Biochem Pharmacol. 2017 Mar 15;128:26-33. doi: 10.1016/j.bcp.2016.12.016. Epub 2016 Dec 23.
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.
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.
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.
黄酮类化合物是人类饮食中常见的营养素，具有多种重要的生物学活性。川陈皮素是一种黄酮类化合物，除了具有抗炎和抗肿瘤活性外，似乎还对心血管系统具有保护作用。多项研究将川陈皮素作为一种天然药物来对抗动脉粥样硬化疾病。相反，关于其在调节动脉粥样硬化的主要急性并发症——血栓形成方面的潜在作用的文献仍然很少。多项研究表明，组织因子（TF）通过触发冠状动脉内血栓的形成，在心血管血栓事件的病理生理学中起关键作用。氧化型低密度脂蛋白（Oxidized-LDL）在促进动脉粥样硬化血栓形成事件中起重要作用。本研究调查了川陈皮素是否可能通过在体外预防人内皮细胞中氧化型低密度脂蛋白介导的组织因子表达而发挥心血管保护作用。此外，我们还研究了川陈皮素的作用是否可能通过抑制核因子κB（NF-κB）途径来调节。
在人脐静脉内皮细胞（HUVEC）中，实时聚合酶链反应（PCR）证明氧化型低密度脂蛋白诱导组织因子mRNA转录，蛋白质免疫印迹法、荧光激活细胞分选术（FACS）分析和促凝血活性测定证明功能活性组织因子表达。川陈皮素通过发挥抗氧化作用预防了这些氧化型低密度脂蛋白介导的作用，最终导致转录因子核因子κB的抑制。
这些数据表明川陈皮素可能是一种潜在的膳食来源抗血栓药物。这种黄酮类化合物通过其抗氧化特性，可能通过抑制在以前从未在此背景下研究过且通常存在于血管壁中的细胞群体（如内皮细胞）中的组织因子表达/活性来发挥抗血栓活性。
