AEE alleviates ox-LDL-induced lipid accumulation and inflammation in macrophages

Ya-Xian Liu; Xi-Wang Liu; Ya-Jun Yang; Shi-Hong Li; Li-Xia Bai; Wen-Bo Ge; Xiao Xu; Cun Li; Jian-Yong Li; Zhe Qin

doi:10.1016/j.biopha.2023.115486

AEE alleviates ox-LDL-induced lipid accumulation and inflammation in macrophages

Biomed Pharmacother. 2023 Nov:167:115486. doi: 10.1016/j.biopha.2023.115486. Epub 2023 Sep 15.

Authors

Ya-Xian Liu¹, Xi-Wang Liu², Ya-Jun Yang², Shi-Hong Li², Li-Xia Bai², Wen-Bo Ge², Xiao Xu², Cun Li³, Jian-Yong Li⁴, Zhe Qin⁵

Affiliations

¹ 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.
² 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.
³ Tianjin Key Laboratory of Agricultural Animal Breeding and Healthy Husbandry, College of Animal Science and Veterinary Medicine, Tianjin Agricultural University, Tianjin 300384, China.
⁴ 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. Electronic address: lijy1971@163.com.
⁵ 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. Electronic address: qinzhe@caas.cn.

PMID: 37708693
DOI: 10.1016/j.biopha.2023.115486

Abstract

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.

Keywords: Aspirin eugenol ester (AEE); Atherosclerosis; Foam cell; NF-κB; PPARγ.