Liu Chao, Guo Qianqian, Lu Mengchen, Li Yunman
State Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Nanjing 210009, PR China.
State Key Laboratory of Natural Medicines, Department of Pharmacochemistry, China Pharmaceutical University, Nanjing 210009, PR China.
Eur J Pharmacol. 2015 Aug 15;761:362-74. doi: 10.1016/j.ejphar.2015.04.015. Epub 2015 May 12.
Prevention or amelioration the prevalence of atherosclerosis has been an effective strategy in the management of cardiovascular diseases. The aim of the study was to scrutinize the effect of Clematichinenoside (AR) on dyslipidemia-induced atherosclerosis and explore its capability on expression of Peroxisome proliferator-activated receptor-α (PPAR-alpha), apolipoprotein A-I (APOA1) and A-II (APOA2), and suppression of apolipoprotein C-III (APOC3) genes and proteins. In the present study, we investigated atherosclerosis effect of AR using a combination of high-fat diet and balloon injury model in rabbits. The levels of biochemical indicators were evaluated in plasma, liver and HepG2 cells using immunoassay technology. In order to expose the underlying mechanism, we evaluated the regulation of PPAR-alpha, APOA1, APOA2 and APOC3 expressions by AR, and we further evaluated the interactions between them after transfection with shRNA (shPPAR-alpha) and, the action of PPAR-alpha in HepG2 cells. We could find that AR markedly promoted the PPAR-alpha transfer from cytoplasm to nucleus which resulted in the alteration of APOA1, APOA2 and APOC3 expressions in HepG2 cells. Moreover, AR significantly reduced total cholesterol, triglycerides and low-density lipoprotein cholesterol (LDL-C) levels, and elevated high-density lipoprotein cholesterol (HDL-C) level, which play an important role in dyslipidemia-induced atherosclerosis. In conclusion, AR ameliorated atherosclerosis via the regulation of hepatic lipid metabolism, and AR also contributed to the activation of PPAR-alpha, APOA1, APOA2 and APOC3. Therefore, AR could be a potential therapeutic agent in the treatment of atherosclerosis.
预防或改善动脉粥样硬化的患病率一直是心血管疾病管理中的有效策略。本研究的目的是仔细研究铁线莲苷（AR）对血脂异常诱导的动脉粥样硬化的影响，并探讨其对过氧化物酶体增殖物激活受体-α（PPAR-α）、载脂蛋白A-I（APOA1）和A-II（APOA2）表达的作用，以及对载脂蛋白C-III（APOC3）基因和蛋白的抑制作用。在本研究中，我们使用高脂饮食和球囊损伤模型联合的方法在兔中研究AR对动脉粥样硬化的影响。使用免疫测定技术评估血浆、肝脏和HepG2细胞中的生化指标水平。为了揭示潜在机制，我们评估了AR对PPAR-α、APOA1、APOA2和APOC3表达的调节作用，并在转染shRNA（shPPAR-α）后进一步评估它们之间的相互作用，以及PPAR-α在HepG2细胞中的作用。我们发现AR显著促进PPAR-α从细胞质转移到细胞核，这导致HepG2细胞中APOA1、APOA2和APOC3表达的改变。此外，AR显著降低总胆固醇、甘油三酯和低密度脂蛋白胆固醇（LDL-C）水平，并提高高密度脂蛋白胆固醇（HDL-C）水平，这些在血脂异常诱导的动脉粥样硬化中起重要作用。总之，AR通过调节肝脏脂质代谢改善动脉粥样硬化，并且AR还促进了PPAR-α、APOA1、APOA2和APOC3的激活。因此，AR可能是治疗动脉粥样硬化的潜在治疗药物。
