Liu Ya-Xian, Liu Xi-Wang, Yang Ya-Jun, Li Shi-Hong, Bai Li-Xia, Ge Wen-Bo, Xu Xiao, Li Cun, Li Jian-Yong, Qin Zhe
Key Lab of New Animal Drug Project of Gansu Province, Key Lab of Veterinary Pharmaceutical Development of Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou 730050, China; Tianjin Key Laboratory of Agricultural Animal Breeding and Healthy Husbandry, College of Animal Science and Veterinary Medicine, Tianjin Agricultural University, Tianjin 300384, China.
Key Lab of New Animal Drug Project of Gansu Province, Key Lab of Veterinary Pharmaceutical Development of Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou 730050, China.
Biomed Pharmacother. 2023 Nov;167:115486. doi: 10.1016/j.biopha.2023.115486. Epub 2023 Sep 15.
Atherosclerosis is a chronic immune inflammatory disease. Aspirin eugenol ester (AEE) is a novel safe and non-toxic compound with many pharmacological effects such as anti-inflammatory, anti-hyperlipidemic and anti-thrombotic action. In order to investigate the effect of AEE on the inhibition of aortic lipid plaque formation and macrophage-derived foam cell formation induced by oxidized low density lipoprotein (ox-LDL), in vivo atherosclerosis model by feeding ApoE mice with a high-fat diet and foam cells formation in vitro model by ox-LDL-induced RAW264.7 macrophages were established. It was found that AEE decreased the levels of TC and LDL-C in serum, and the plaque formation area and lipid accumulation in the aortic intima of ApoE mice. In vitro studies showed that AEE could prevent the uptake of ox-LDL and reduce the contents of TC and FC in cells. AEE enhanced the cholesterol efflux by increasing the expression of ABCA1, ABCG1 and PPARγ, which effectively alleviated excess cholesterol accumulated in the cells. Meanwhile, AEE also reduced the secretion and expression of inflammatory factors in the cells. In addition, AEE could reverse the action of PPARγ inhibitor T0070907 and/or ox-LDL. Therefore, AEE may become an effective candidate drug for the prevention of atherosclerosis.
动脉粥样硬化是一种慢性免疫炎症性疾病。阿司匹林丁香酚酯（AEE）是一种新型的安全无毒化合物，具有多种药理作用，如抗炎、抗高血脂和抗血栓形成作用。为了研究AEE对抑制氧化低密度脂蛋白（ox-LDL）诱导的主动脉脂质斑块形成和巨噬细胞源性泡沫细胞形成的影响，建立了通过给载脂蛋白E（ApoE）小鼠喂食高脂饮食的体内动脉粥样硬化模型以及通过ox-LDL诱导RAW264.7巨噬细胞的体外泡沫细胞形成模型。结果发现，AEE降低了血清中总胆固醇（TC）和低密度脂蛋白胆固醇（LDL-C）的水平，以及ApoE小鼠主动脉内膜的斑块形成面积和脂质蓄积。体外研究表明AEE可阻止ox-LDL的摄取并降低细胞内TC和游离胆固醇（FC）的含量。AEE通过增加ATP结合盒转运体A1（ABCA1）、ATP结合盒转运体G1（ABCG1）和过氧化物酶体增殖物激活受体γ（PPARγ）的表达来增强胆固醇外流，从而有效减轻细胞内过量蓄积的胆固醇。同时，AEE还降低了细胞内炎症因子的分泌和表达。此外，AEE可逆转PPARγ抑制剂T0070907和/或ox-LDL的作用。因此，AEE可能成为预防动脉粥样硬化的有效候选药物。
