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Here, we found that high glucose (<jats:styled-content style=\"fixed-case\">HG<\/jats:styled-content>) induced myocardial damage by activating the <jats:styled-content style=\"fixed-case\">NLRP<\/jats:styled-content>3 inflammasome and then promoting <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101\u03b2 and <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201018 secretion in H9C2 cells and <jats:styled-content style=\"fixed-case\">NRVM<\/jats:styled-content>s. Meanwhile, <jats:styled-content style=\"fixed-case\">HG<\/jats:styled-content> elevated the production of <jats:styled-content style=\"fixed-case\">ROS<\/jats:styled-content>, which was vital to <jats:styled-content style=\"fixed-case\">NLRP<\/jats:styled-content>3 inflammasome activation. Moreover, the <jats:styled-content style=\"fixed-case\">ROS<\/jats:styled-content> activated the <jats:styled-content style=\"fixed-case\">NLRP<\/jats:styled-content>3 inflammasome mainly by cytochrome <jats:italic>c<\/jats:italic> influx into the cytoplasm and binding to <jats:styled-content style=\"fixed-case\">NLRP<\/jats:styled-content>3. Inhibition of <jats:styled-content style=\"fixed-case\">ROS<\/jats:styled-content> and cytochrome <jats:italic>c<\/jats:italic> dramatically down\u2010regulated <jats:styled-content style=\"fixed-case\">NLRP<\/jats:styled-content>3 inflammasome activation and improved the cardiomyocyte damage induced by <jats:styled-content style=\"fixed-case\">HG<\/jats:styled-content>, which was also detected in cells treated by <jats:italic>Gps<\/jats:italic>. Furthermore, <jats:italic>Gps<\/jats:italic> also reduced the levels of the C\u2010reactive proteins (<jats:styled-content style=\"fixed-case\">CRP<\/jats:styled-content>s), <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101\u03b2 and <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201018, inhibited <jats:styled-content style=\"fixed-case\">NLRP<\/jats:styled-content>3 inflammasome activation and consequently improved myocardial damage in\u00a0vivo. These findings provide a mechanism that <jats:styled-content style=\"fixed-case\">ROS<\/jats:styled-content> induced by <jats:styled-content style=\"fixed-case\">HG<\/jats:styled-content> activates the <jats:styled-content style=\"fixed-case\">NLRP<\/jats:styled-content>3 inflammasome by cytochrome <jats:italic>c<\/jats:italic> binding to <jats:styled-content style=\"fixed-case\">NLRP<\/jats:styled-content>3 and that <jats:italic>Gps<\/jats:italic> may be potential and effective drugs for <jats:styled-content style=\"fixed-case\">DCM<\/jats:styled-content> via the inhibition of <jats:styled-content style=\"fixed-case\">ROS<\/jats:styled-content>\u2010mediated <jats:styled-content style=\"fixed-case\">NLRP<\/jats:styled-content>3 inflammasome activation.<\/jats:p>","DOI":"10.1111\/jcmm.13743","type":"journal-article","created":{"date-parts":[[2018,7,11]],"date-time":"2018-07-11T10:52:51Z","timestamp":1531306371000},"page":"4437-4448","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":138,"title":["Gypenosides improve diabetic cardiomyopathy by inhibiting <scp>ROS<\/scp>\u2010mediated <scp>NLRP<\/scp>3 inflammasome activation"],"prefix":"10.1111","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3316-4290","authenticated-orcid":false,"given":"Hailong","family":"Zhang","sequence":"first","affiliation":[{"name":"Joint National Laboratory for Antibody Drug Engineering Key Laboratory of Cellular and Molecular Immunology of Henan Province School of Basic Medicine Henan University Kaifeng China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of General Pathology 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