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Targeting key proteins in inflammatory signaling may provide new therapy for DCM. In this study, the authors explore the pharmacological effects and mechanisms of Schisandrin B (Sch\u00a0B), a natural compound with anti\u2010inflammatory activity against DCM. It is shown that Sch\u00a0B prevents high\u2010level glucose (HG)\u2010induced hypertrophic and fibrotic responses in cultured cardiomyocytes. RNA sequencing and inflammatory qPCR microarray show that Sch\u00a0B mainly affects myeloid differentiation primary response 88 (MyD88)\u2010dependent inflammatory gene expression in HG\u2010challenged cardiomyocytes. Further studies indicate that Sch\u00a0B directly binds to and inhibits MyD88 activation, but does not alter MyD88\u2010independent Toll\u2010like receptor signaling in\u00a0vivo and in\u00a0vitro. Inhibiting or silencing MyD88 is associated with reduced levels of HG\u2010induced inflammatory cytokines and myocardial injuries in\u00a0vitro. Treatment of type\u00a01 and type\u00a02 diabetic mice with Sch\u00a0B protects heart function, reduces myocardial injuries, and decreases secretion of inflammatory cytokines. Cardiomyocyte\u2010specific MyD88 knockout also protects mice against cardiac inflammation and injury in type\u00a01 diabetic mice. In conclusion, these studies show that cardiomyocyte MyD88 plays an apathogenetic role in DCM and Sch\u00a0B specifically targets MyD88 to reduce inflammatory DCM.<\/jats:p>","DOI":"10.1002\/advs.202202590","type":"journal-article","created":{"date-parts":[[2022,9,30]],"date-time":"2022-09-30T22:52:19Z","timestamp":1664578339000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":64,"title":["Schisandrin B Attenuates Diabetic Cardiomyopathy by Targeting MyD88 and Inhibiting MyD88\u2010Dependent Inflammation"],"prefix":"10.1002","volume":"9","author":[{"given":"Wu","family":"Luo","sequence":"first","affiliation":[{"name":"Chemical Biology Research Center School of Pharmaceutical Sciences Wenzhou Medical University  Wenzhou Zhejiang 325035 China"},{"name":"School of Pharmaceutical Sciences Hangzhou Medical College  Hangzhou Zhejiang 311399 China"},{"name":"Department of Cardiology and Medical Research Center the First Affiliated 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