State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.
Circ J. 2012;76(4):995-1003. doi: 10.1253/circj.cj-11-0344. Epub 2012 Jan 28.
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.
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)-κB 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-κB signaling pathway.
CRA is capable of ameliorating atherosclerosis in apolipoprotein E-deficient mice by, partly at least, inhibition of NF-κB activity along with decreased MCP-1 expression.
熊果酸（CRA）是一种五环三萜酸，已被证明在添加到低密度脂蛋白缺乏的小鼠饮食中时具有抗动脉粥样硬化作用，但作用机制尚不清楚。本研究的目的是探讨 CRA 改善动脉粥样硬化的分子机制。
采用载脂蛋白 E 缺陷小鼠的 Western 饮食模型评估 CRA 对动脉粥样硬化的抑制作用，通过动脉粥样硬化病变面积、血清谱、基因表达和组织学病变进行评价。体外，在脂多糖诱导的炎症模型上研究 CRA 抗炎作用的机制。该模型还用于详细研究 CRA 对基因表达和核因子（NF）-κB 激活的影响。与对照组相比，CRA 处理组的动脉粥样硬化病变面积明显减少，单核细胞趋化蛋白 1（MCP-1）和 CCR2 的表达也减少。体外研究表明，CRA 处理可下调 MCP-1 的 mRNA 水平，并抑制单核细胞黏附和迁移，同时抑制 NF-κB 信号通路。
CRA 通过抑制 NF-κB 活性和降低 MCP-1 的表达，至少部分缓解载脂蛋白 E 缺陷小鼠的动脉粥样硬化。
