Corosolic Acid Ameliorates Atherosclerosis in Apolipoprotein E-Deficient Mice by Regulating the Nuclear Factor-κB Signaling Pathway and Inhibiting Monocyte Chemoattractant Protein-1 Expression
Corosolic Acid Ameliorates Atherosclerosis in Apolipoprotein E-Deficient Mice by Regulating the Nuclear Factor-κB Signaling Pathway and Inhibiting Monocyte Chemoattractant Protein-1 Expression
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DOI：
10.1253/circj.cj-11-0344
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发表时间：
2012-04-01
影响因子：
3.3
通讯作者：
Wang, Qiang
中科院分区：
文献类型：
--
作者：
Chen, Hong;Yang, Jie;Wang, Qiang
背景资料：科罗索酸（Corosolic acid，CRA）是一种五环三萜酸，添加到低密度脂蛋白缺乏小鼠的饮食中具有抗动脉粥样硬化作用，但其作用机制尚不清楚。本研究的目的是探讨CRA改善动脉粥样硬化的分子机制。方法和结果：CRA的抗动脉粥样硬化作用的载脂蛋白E-缺陷小鼠喂养西式饮食进行了评估，动脉粥样硬化病变面积，血清配置文件，基因表达和组织学病变。在体外，CRA的抗炎作用的机制进行了研究的脂多糖诱导的炎症模型。该模型还被用来详细研究CRA对基因表达和核因子（NF）-κ B活化的影响。与对照组相比，CRA治疗组显示动脉粥样硬化病变面积以及单核细胞趋化蛋白-1（MCP-1）和CCR 2的表达显著减少。体外研究表明，CRA治疗下调MCP-1的mRNA水平，并抑制单核细胞粘附和迁移，连同抑制NF-κ B信号pathway.Conclusions：CRA是能够改善载脂蛋白E缺陷小鼠动脉粥样硬化的，至少部分，抑制NF-κ B活性沿着降低MCP-1的表达。(Circ J 2012; 76：995-1003）
Background: Corosolic acid (CRA) is a pentacyclic triterpene acid that has been shown to exhibit an anti-atherosclerotic effect when added to diets of low-density lipoprotein-deficient mice, but the mechanisms are unclear. The purpose of the present study was to investigate the molecular mechanisms by which CRA ameliorates atherosclerosis.Methods and Results: The anti-atherosclerosis effect of CRA in apolipoprotein E-deficient mice fed a Western-type diet was evaluated using atherosclerosis lesion area, serum profiles, gene expression and histological lesions. In vitro, the mechanisms responsible for the anti-inflammatory effect of CRA were investigated on a lipopolysaccharide-induced inflammation model. This model was also used to investigate in detail the effects of CRA on gene expression and nuclear factor (NF)-kappa B activation. Compared with the control group, the CRA-treated group exhibited a significant decrease in atherosclerotic lesion area, as well as expression of monocyte chemoattractant protein-1 (MCP-1) and CCR2. In vitro studies showed that CRA treatment downregulated the mRNA levels of MCP-1, and inhibited monocyte adhesion and migration, together with suppression of NF-kappa B signaling pathway.Conclusions: CRA is capable of ameliorating atherosclerosis in apolipoprotein E-deficient mice by, partly at least, inhibition of NF-kappa B activity along with decreased MCP-1 expression. (Circ J 2012; 76: 995-1003)