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Alpha\u2010mangostin has been reported to have anti\u2010diabetic capacity in recent years. Here, we investigated the protective function of alpha\u2010mangostin on endothelium in vitro and in vivo experiments. We also observed that alpha\u2010mangostin improved impaired endothelium\u2010dependent vasodilation (EDV) of diabetic animals while it limited the aSMase\/ceramide pathway and up\u2010regulated eNOS\/NO pathway in aortas from diabetic mice. Meanwhile, alpha\u2010mangostin inhibited elevated aSMase\/ceramide pathway and reversed impaired EDV induced by high glucose in isolated mouse aortas. In addition, alpha\u2010mangostin increased phosphorylation of eNOS and NO production in high glucose\u2010treated aortas. Alpha\u2010mangostin normalized high glucose\u2010induced activation of aSMase\/ceramide pathway and improved eNOS\/NO pathway in endothelial cells with high glucose. In conclusion, alpha\u2010mangostin regulates eNOS\/NO pathway and improves EDV in aortas of diabetic mice through inhibiting aSMase activity and endogenous ceramide accumulation.<\/jats:p>","DOI":"10.1111\/jcmm.16456","type":"journal-article","created":{"date-parts":[[2021,3,14]],"date-time":"2021-03-14T22:05:36Z","timestamp":1615759536000},"page":"3601-3609","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Alpha\u2010mangostin improves endothelial dysfunction in\n                    <i>db\/db<\/i>\n                    mice through inhibition of aSMase\/ceramide pathway"],"prefix":"10.1111","volume":"25","author":[{"given":"Meng","family":"Jiang","sequence":"first","affiliation":[{"name":"Xiangya Hospital of Central South University Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanya","family":"Huang","sequence":"additional","affiliation":[{"name":"Xiangya Hospital of Central 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