{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T18:54:15Z","timestamp":1768762455321,"version":"3.49.0"},"reference-count":102,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T00:00:00Z","timestamp":1768435200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National natural science foundation","doi-asserted-by":"crossref","award":["32273069"],"award-info":[{"award-number":["32273069"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Vascular endothelial injury is a key pathological characteristic of multiple diseases, such as atherosclerosis, stroke, and mastitis. Aspirin eugenol ester (AEE) has been confirmed to exert a significant protective effect on vascular endothelial injury. However, the universal action patterns and underlying mechanisms of AEE across different pathological scenarios have not been systematically elucidated. This study aimed to investigate the effect and mechanism of AEE in alleviating multiple vascular endothelial injury models. Nine vascular endothelial injury models were established by treating bovine aortic endothelial cells (BAECs), mouse aortic endothelial cells (MAECs), and human umbilical vein endothelial cells (Huvecs) with ethanol (EtOH), hydrogen peroxide (H2O2), and copper sulfate (CuSO4), respectively. The protective effects of AEE were systematically evaluated via morphological observation, detection of inflammatory responses, and oxidative stress markers. Furthermore, metabolomics was employed to identify and analyze differentially expressed metabolites between the nine model groups and AEE groups. AEE exerted protective effects on all nine vascular endothelial injury models, inhibiting inflammation and oxidative stress induced by all inducers. Metabolomic analysis revealed that the differentially expressed metabolites modulated by AEE in most models were primarily enriched in lipid metabolism, amino acid metabolism, coenzyme biosynthesis, and other related pathways. AEE could improve vascular endothelial injury by upregulating antioxidant substance which included eicosapentaenoic acid (EPA), choline, coenzyme A (CoA), glutathione (GSH), catalase (CAT) and superoxide dismutase (SOD), as well as downregulating substances that cause endothelial oxidative damage, including phytosphingosine (PS), palmitic acid (PA), and arachidonic acid (AA).<\/jats:p>","DOI":"10.3390\/ijms27020877","type":"journal-article","created":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T12:31:41Z","timestamp":1768480301000},"page":"877","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multicellular Model Reveals the Mechanism of AEE Alleviating Vascular Endothelial Cell Injury via Anti-Inflammatory and Antioxidant Effects"],"prefix":"10.3390","volume":"27","author":[{"given":"Ji","family":"Feng","sequence":"first","affiliation":[{"name":"Key Lab of New Animal Drug 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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Tao","sequence":"additional","affiliation":[{"name":"Key Lab of New Animal Drug 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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meng-Zhen","family":"Li","sequence":"additional","affiliation":[{"name":"Key Lab of New Animal Drug 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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhi-Jie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Lab of New Animal Drug 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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qin-Fang","family":"Yu","sequence":"additional","affiliation":[{"name":"Key Lab of New Animal Drug 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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3317-0666","authenticated-orcid":false,"given":"Jian-Yong","family":"Li","sequence":"additional","affiliation":[{"name":"Key Lab of New Animal Drug 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"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Asatiani, N., Sapojnikova, N., Kartvelishvili, T., Asanishvili, L., Sichinava, N., and Chikovani, Z. 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