Department of Pharmaceutical, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, 510080, China; Department of Clinical Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510080, China.
School of Traditional Chinese Medicine, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou, 510515, China.
Biomed Pharmacother. 2018 Jan;97:1694-1700. doi: 10.1016/j.biopha.2017.11.151. Epub 2017 Dec 8.
Atherosclerosis, the leading cause of cardiovascular diseases in the world, is a chronic inflammatory disorder characterized by the dysfunction of arteries. Oleanolic acid (OA) is a bioactive nature product which exists in various plants and herbs. Previous studies have demonstrated that OA was involved in numerous of biological processes, including atherosclerosis. However, the exact mechanisms of the anti-atherosclerosis effects of OA remain unknown. Here, in our study, we analyzed the effects and possible underlying mechanisms of OA in atherosclerosis depending a cell model and an animal model of atherosclerosis. Human umbilical vein endothelial cells (HUVECs) were treated with oxidized low-density lipoprotein (ox-LDL, 100 μg/mL) for 24 h to establish an atherosclerotic cell model. New Zealand white (NZW) rabbits were fed with high-fat (HF) diets for three months to establish an atherosclerotic animal model. Then, cell viability and expression of cytokines (ANG, NO, eNOS, IL-1β, TNF-α, and IL-6) were measured with CCK-8 assay and ELISA kits, cell apoptosis and cell cycle distribution were analyzed by flow cytometry in the atherosclerotic cell model. Results showed that ox-LDL induced effects of anti-proliferation, cytokines alterations, and cell apoptosis were abolished by the application of OA or Ang (1-7). Further study indicated that OA increased the expression of ANG by upregulating the FXR expression in the ox-LDL induced HUVECs arthrosclerosis model. And the in vivo experiment in the HF diet induced animal model suggested that OA may inhibit the development of atherosclerosis. The atherosclerosis of aortas was assessed by Hematoxylin Eosin (HE), Oil Red O and Picrosirius Red staining; the expression levels of total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C), and high density lipoprotein cholesterol (HDL-C) were determined by the fully automatic biochemical analyzer, in the atherosclerotic animal model. All the results showed that OA treatment improved the cell viability in the cell model, inhibited the atherosclerosis development in the animal model. OA play as an anti-atherosclerosis agent in both the cell model and animal model by upregulating the production of Angiotensin (Ang)-(1-7) through FXR.
动脉粥样硬化是世界范围内心血管疾病的主要病因，是一种以动脉功能障碍为特征的慢性炎症性疾病。齐墩果酸（OA）是一种存在于多种植物和草药中的生物活性天然产物。先前的研究表明，OA 参与了许多生物学过程，包括动脉粥样硬化。然而，OA 抗动脉粥样硬化作用的确切机制尚不清楚。在本研究中，我们通过细胞模型和动脉粥样硬化动物模型分析了 OA 在动脉粥样硬化中的作用及其可能的潜在机制。用氧化型低密度脂蛋白（ox-LDL，100μg/mL）处理人脐静脉内皮细胞（HUVECs）24 h 建立动脉粥样硬化细胞模型。用高脂（HF）饮食喂养新西兰白兔 3 个月建立动脉粥样硬化动物模型。然后，用 CCK-8 法和 ELISA 试剂盒测定细胞活力和细胞因子（ANG、NO、eNOS、IL-1β、TNF-α和 IL-6）的表达，用流式细胞术分析细胞凋亡和细胞周期分布在动脉粥样硬化细胞模型中。结果表明，ox-LDL 诱导的抗增殖作用、细胞因子改变和细胞凋亡作用被 OA 或 Ang（1-7）的应用所消除。进一步的研究表明，OA 通过上调 ox-LDL 诱导的 HUVECs 动脉粥样硬化模型中 FXR 的表达，增加 ANG 的表达。HF 饮食诱导的动物模型中的体内实验表明，OA 可能抑制动脉粥样硬化的发展。通过苏木精和伊红（HE）、油红 O 和苦味酸天狼猩红染色评估主动脉粥样硬化；用全自动生化分析仪测定总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）和高密度脂蛋白胆固醇（HDL-C）的表达水平，在动脉粥样硬化动物模型中。所有结果表明，OA 处理改善了细胞模型中的细胞活力，抑制了动物模型中的动脉粥样硬化发展。OA 通过 FXR 上调血管紧张素（Ang）-（1-7）的产生，在细胞模型和动物模型中发挥抗动脉粥样硬化作用。
