PDF(Pubmed)
Abstract：
The accumulation of oxidized low-density lipoprotein (oxLDL) and its toxicity in the arterial wall have been implicated in atherosclerosis. This study aimed to investigate the mechanisms underlying the atheroprotective effect of bixin, a carotenoid obtained from the seeds of the tropical plant Bixa orellana, on Cu2+-induced LDL oxidation and oxLDL-mediated effects in J774A.1 macrophage cells. Bixin\'s effects were compared to those of lycopene, a carotenoid widely studied for its cardiovascular protective effects. LDL was isolated from human plasma, incubated with bixin or lycopene (positive control), and subjected to oxidation with CuSO4. Afterward, bixin or lycopene was incubated with J774A.1 macrophage cells and exposed to oxLDL. The levels of ROS, RNS, GSH, nitrite, mitochondrial function, and foam cell formation, as well as the expression of proteins related to the antioxidant and inflammatory status, were evaluated. The effect of bixin in inhibiting in vitro human-isolated LDL oxidation was more potent (5-6-fold) than that of lycopene. Bixin pretreatment reduced the atherogenic signaling triggered by oxLDL in the macrophages, namely the generation of reactive species, disturbance of nitric oxide homeostasis, mitochondrial dysfunction, and foam cell formation. The cytoprotective effects of bixin were accompanied by the upregulation of Nrf2 and the downregulation of the NF-kB pathways. Lycopene showed the same protective effect as bixin, except that it did not prevent mitochondrial dysfunction. The efficient performance of bixin makes it an ideal candidate for further trials as a new nutraceutical compound for the prevention of atherosclerosis.
摘要：
动脉粥样硬化与氧化低密度脂蛋白（oxLDL）的积累及其在动脉壁中的毒性有关。本研究旨在探讨Bixin的动脉粥样硬化保护作用的潜在机制，从热带植物Bixaorellana的种子中获得的类胡萝卜素，在J774A.1巨噬细胞中Cu2诱导的LDL氧化和oxLDL介导的作用。将Bixin的作用与番茄红素的作用进行了比较，一种因心血管保护作用而被广泛研究的类胡萝卜素。LDL从人血浆中分离，与Bixin或番茄红素（阳性对照）一起孵育，并用CuSO4进行氧化。之后,将Bixin或番茄红素与J774A.1巨噬细胞一起孵育并暴露于oxLDL。ROS的水平，RNS,GSH,亚硝酸盐,线粒体功能，和泡沫细胞的形成，以及与抗氧化和炎症状态相关的蛋白质的表达，进行了评估。Bixin抑制体外人分离的LDL氧化的作用比番茄红素更有效（5-6倍）。Bixin预处理减少了巨噬细胞中oxLDL引发的动脉粥样硬化信号，即反应性物种的产生，一氧化氮稳态紊乱，线粒体功能障碍，和泡沫细胞的形成。Bixin的细胞保护作用伴随着Nrf2的上调和NF-kB途径的下调。番茄红素表现出与Bixin相同的保护作用，除了它不能预防线粒体功能障碍。Bixin的有效性能使其成为进一步试验的理想候选者，作为预防动脉粥样硬化的新营养化合物。
