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It exerts both anti\u2010inflammatory and antioxidant pharmacological properties. However, little is known about the effect of SYR on modulating diabetic cardiomyopathy. The present study aimed to investigate the pharmacodynamic effect of SYR on diabetic cardiomyopathy and the underlying molecular mechanism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and Results<\/jats:title><jats:p>In STZ\u2010induced type 1 diabetic mice, orally administration with SYR in every other day for 8 weeks significantly improves cardiac dysfunction and preventes cardiac hypertrophy and fibrosis. The macrophage infiltration and oxidative stress biomarkers are also suppressed by SYR without affecting hyperglycemia and body weight. In neonatal cardiomyocytes, high glucose\u2010induced cell apoptosis and fibrosis are potently decreased by SYR, and the inflammatory response and oxidant stress are also alleviated by SYR incubation. Mechanistically, SYR may exert protective effects by restoring suppression of antioxidant kelch\u2010like ECH\u2010associated protein 1 (Keap1)\/nuclear factor\u2010E2\u2010related factor 2 (Nrf2) system and abnormal activation of transforming growth factor\u2010\u03b2 (TGF\u2010\u03b2)\/mothers against decapentaplegic homolog (Smad) signaling pathway in vitro and in vivo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The results indicated that SYR could be a potential therapeutic agent for the treatment of diabetic cardiomyopathy by inhibiting inflammation, fibrosis, and oxidative stress. The signaling pathway of Keap1\/Nrf2 and TGF\u2010\u03b2\/Smad could be used as therapeutic targets for diabetic complications.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mnfr.202000231","type":"journal-article","created":{"date-parts":[[2020,7,30]],"date-time":"2020-07-30T13:37:53Z","timestamp":1596116273000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Syringaresinol Protects against Type 1 Diabetic Cardiomyopathy by Alleviating Inflammation Responses, Cardiac Fibrosis, and Oxidative Stress"],"prefix":"10.1002","volume":"64","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8242-6977","authenticated-orcid":false,"given":"Guangru","family":"Li","sequence":"first","affiliation":[{"name":"Department of Pharmacology, School of Medicine Nankai University  Tianjin 300071 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Yang","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair, Institute of Acute Abdominal Diseases Tianjin Nankai Hospital  Tianjin 300100 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lifeng","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine Nankai University  Tianjin 300071 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiu","family":"Yang","sequence":"additional","affiliation":[{"name":"Clinical laboratory First Teaching Hospital of Tianjin University of Traditional Chinese Medicine  Tianjin 300197 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yafei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine Nankai University  Tianjin 300071 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiale","family":"An","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine Nankai University  Tianjin 300071 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dihua","family":"Li","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair, Institute of Acute Abdominal Diseases Tianjin Nankai Hospital  Tianjin 300100 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine Nankai University  Tianjin 300071 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine Nankai University  Tianjin 300071 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine Nankai University  Tianjin 300071 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine Nankai University  Tianjin 300071 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine Nankai University  Tianjin 300071 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Qi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine Nankai University  Tianjin 300071 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,8,9]]},"reference":[{"key":"e_1_2_7_1_1","first-page":"151","volume":"6","author":"Chavali V.","year":"2013","journal-title":"Diabetes, Metab. 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