{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T10:04:20Z","timestamp":1790417060323,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2016,4,15]],"date-time":"2016-04-15T00:00:00Z","timestamp":1460678400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81472030"],"award-info":[{"award-number":["81472030"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81472454"],"award-info":[{"award-number":["81472454"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31100930"],"award-info":[{"award-number":["31100930"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81572082"],"award-info":[{"award-number":["81572082"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Diabetes Invest"],"published-print":{"date-parts":[[2016,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims\/Introduction<\/jats:title><jats:p>An elevated level of plasma homocysteine has long been suspected as a metabolic risk factor for the development of atherosclerotic vascular diseases in diabetes. Berberine (<jats:styled-content style=\"fixed-case\">BBR<\/jats:styled-content>) has several preventive effects on cardiovascular diseases. The effects of <jats:styled-content style=\"fixed-case\">BBR<\/jats:styled-content> on atherosclerotic plaque stability increased by homocysteine thiolactone (<jats:styled-content style=\"fixed-case\">HTL<\/jats:styled-content>) remain unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>The model of atherosclerotic vulnerable plaque was induced by placing a collar around the carotid artery in <jats:italic>Apoe<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice. Endothelium\u2010dependent relaxation was assayed by organ chamber.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Homocysteine thiolactone (50 mg\/kg\/day, 8 weeks) reduced the atherosclerotic plaque stability in the carotid artery of <jats:italic>Apoe<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice, which was reversed by <jats:styled-content style=\"fixed-case\">BBR<\/jats:styled-content> administration (1.0 g\/kg\/day). <jats:italic>In vivo<\/jats:italic> and <jats:italic>ex vivo<\/jats:italic> experiments showed that <jats:styled-content style=\"fixed-case\">HTL<\/jats:styled-content> dramatically reduced acetylcholine\u2010induced endothelium\u2010dependent relaxation and superoxide dismutase activity, and increased malondialdehyde content, which were inhibited by <jats:styled-content style=\"fixed-case\">BBR<\/jats:styled-content>. Importantly, all effects induced by <jats:styled-content style=\"fixed-case\">BBR<\/jats:styled-content> were abolished by <jats:styled-content style=\"fixed-case\">GW<\/jats:styled-content>9662, an antagonist of peroxisome proliferator\u2010activated receptor\u2010\u03b3. Incubation of cultured endothelial cells with <jats:styled-content style=\"fixed-case\">HTL<\/jats:styled-content> significantly reduced cell viabilities and enhanced production of reactive oxygen species. Pretreatment of cells with <jats:styled-content style=\"fixed-case\">BBR<\/jats:styled-content> dose\u2010dependently reversed <jats:styled-content style=\"fixed-case\">HTL<\/jats:styled-content>\u2010induced detrimental effects, which were <jats:styled-content style=\"fixed-case\">GW<\/jats:styled-content>9662\u2010reversible.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Berberine increases atherosclerotic plaque stability in hyperhomocysteinemia mice, which is related to the activation of peroxisome proliferator\u2010activated receptor\u2010\u03b3 and subsequent suppression of oxidative stress in endothelial cells.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jdi.12516","type":"journal-article","created":{"date-parts":[[2016,3,7]],"date-time":"2016-03-07T09:50:53Z","timestamp":1457344253000},"page":"824-832","source":"Crossref","is-referenced-by-count":43,"title":["Berberine activates peroxisome proliferator\u2010activated receptor gamma to increase atherosclerotic plaque stability in <i>Apoe<\/i><sup><i>\u2212\/\u2212<\/i><\/sup> mice with hyperhomocysteinemia"],"prefix":"10.1111","volume":"7","author":[{"given":"Hongjun","family":"Li","sequence":"first","affiliation":[{"name":"China\u2010Japan Union Hospital Jilin University Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengyan","family":"He","sequence":"additional","affiliation":[{"name":"China\u2010Japan Union Hospital Jilin University Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingying","family":"Wang","sequence":"additional","affiliation":[{"name":"China\u2010Japan Union Hospital Jilin University Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoou","family":"Li","sequence":"additional","affiliation":[{"name":"Tumor Hospital of Jilin Province The Second Hospital of Jilin University Changchun 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