Schisandrin B Attenuates Diabetic Cardiomyopathy by Targeting MyD88 and Inhibiting MyD88‐Dependent Inflammation
Abstract Diabetes manifests as chronic inflammation and leads to the development diabetic cardiomyopathy (DCM). 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 B), a...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-11-01
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| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202202590 |
| _version_ | 1797990324854849536 |
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| author | Wu Luo Ke Lin Junyi Hua Jibo Han Qiuyan Zhang Lingfeng Chen Zia A. Khan Gaojun Wu Yi Wang Guang Liang |
| author_facet | Wu Luo Ke Lin Junyi Hua Jibo Han Qiuyan Zhang Lingfeng Chen Zia A. Khan Gaojun Wu Yi Wang Guang Liang |
| author_sort | Wu Luo |
| collection | DOAJ |
| description | Abstract Diabetes manifests as chronic inflammation and leads to the development diabetic cardiomyopathy (DCM). 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 B), a natural compound with anti‐inflammatory activity against DCM. It is shown that Sch B prevents high‐level glucose (HG)‐induced hypertrophic and fibrotic responses in cultured cardiomyocytes. RNA sequencing and inflammatory qPCR microarray show that Sch B mainly affects myeloid differentiation primary response 88 (MyD88)‐dependent inflammatory gene expression in HG‐challenged cardiomyocytes. Further studies indicate that Sch B directly binds to and inhibits MyD88 activation, but does not alter MyD88‐independent Toll‐like receptor signaling in vivo and in vitro. Inhibiting or silencing MyD88 is associated with reduced levels of HG‐induced inflammatory cytokines and myocardial injuries in vitro. Treatment of type 1 and type 2 diabetic mice with Sch B protects heart function, reduces myocardial injuries, and decreases secretion of inflammatory cytokines. Cardiomyocyte‐specific MyD88 knockout also protects mice against cardiac inflammation and injury in type 1 diabetic mice. In conclusion, these studies show that cardiomyocyte MyD88 plays an apathogenetic role in DCM and Sch B specifically targets MyD88 to reduce inflammatory DCM. |
| first_indexed | 2024-04-11T08:33:39Z |
| format | Article |
| id | doaj.art-c1c7750e56114b77a9290ad9d1c5ba39 |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-04-11T08:33:39Z |
| publishDate | 2022-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-c1c7750e56114b77a9290ad9d1c5ba392022-12-22T04:34:24ZengWileyAdvanced Science2198-38442022-11-01931n/an/a10.1002/advs.202202590Schisandrin B Attenuates Diabetic Cardiomyopathy by Targeting MyD88 and Inhibiting MyD88‐Dependent InflammationWu Luo0Ke Lin1Junyi Hua2Jibo Han3Qiuyan Zhang4Lingfeng Chen5Zia A. Khan6Gaojun Wu7Yi Wang8Guang Liang9Chemical Biology Research Center School of Pharmaceutical Sciences Wenzhou Medical University Wenzhou Zhejiang 325035 ChinaChemical Biology Research Center School of Pharmaceutical Sciences Wenzhou Medical University Wenzhou Zhejiang 325035 ChinaDepartment of Cardiovascular Medicine the Second Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine Hangzhou Zhejiang 310009 ChinaChemical Biology Research Center School of Pharmaceutical Sciences Wenzhou Medical University Wenzhou Zhejiang 325035 ChinaChemical Biology Research Center School of Pharmaceutical Sciences Wenzhou Medical University Wenzhou Zhejiang 325035 ChinaSchool of Pharmaceutical Sciences Hangzhou Medical College Hangzhou Zhejiang 311399 ChinaDepartment of Pathology and Laboratory Medicine University of Western Ontario London Ontario N6A 5C1 CanadaDepartment of Cardiology and Medical Research Center the First Affiliated Hospital Wenzhou Medical University Wenzhou Zhejiang 325035 ChinaChemical Biology Research Center School of Pharmaceutical Sciences Wenzhou Medical University Wenzhou Zhejiang 325035 ChinaChemical Biology Research Center School of Pharmaceutical Sciences Wenzhou Medical University Wenzhou Zhejiang 325035 ChinaAbstract Diabetes manifests as chronic inflammation and leads to the development diabetic cardiomyopathy (DCM). 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 B), a natural compound with anti‐inflammatory activity against DCM. It is shown that Sch B prevents high‐level glucose (HG)‐induced hypertrophic and fibrotic responses in cultured cardiomyocytes. RNA sequencing and inflammatory qPCR microarray show that Sch B mainly affects myeloid differentiation primary response 88 (MyD88)‐dependent inflammatory gene expression in HG‐challenged cardiomyocytes. Further studies indicate that Sch B directly binds to and inhibits MyD88 activation, but does not alter MyD88‐independent Toll‐like receptor signaling in vivo and in vitro. Inhibiting or silencing MyD88 is associated with reduced levels of HG‐induced inflammatory cytokines and myocardial injuries in vitro. Treatment of type 1 and type 2 diabetic mice with Sch B protects heart function, reduces myocardial injuries, and decreases secretion of inflammatory cytokines. Cardiomyocyte‐specific MyD88 knockout also protects mice against cardiac inflammation and injury in type 1 diabetic mice. In conclusion, these studies show that cardiomyocyte MyD88 plays an apathogenetic role in DCM and Sch B specifically targets MyD88 to reduce inflammatory DCM.https://doi.org/10.1002/advs.202202590cardiomyocytesdiabetic cardiomyopathyinflammationMyD88Schisandrin B |
| spellingShingle | Wu Luo Ke Lin Junyi Hua Jibo Han Qiuyan Zhang Lingfeng Chen Zia A. Khan Gaojun Wu Yi Wang Guang Liang Schisandrin B Attenuates Diabetic Cardiomyopathy by Targeting MyD88 and Inhibiting MyD88‐Dependent Inflammation Advanced Science cardiomyocytes diabetic cardiomyopathy inflammation MyD88 Schisandrin B |
| title | Schisandrin B Attenuates Diabetic Cardiomyopathy by Targeting MyD88 and Inhibiting MyD88‐Dependent Inflammation |
| title_full | Schisandrin B Attenuates Diabetic Cardiomyopathy by Targeting MyD88 and Inhibiting MyD88‐Dependent Inflammation |
| title_fullStr | Schisandrin B Attenuates Diabetic Cardiomyopathy by Targeting MyD88 and Inhibiting MyD88‐Dependent Inflammation |
| title_full_unstemmed | Schisandrin B Attenuates Diabetic Cardiomyopathy by Targeting MyD88 and Inhibiting MyD88‐Dependent Inflammation |
| title_short | Schisandrin B Attenuates Diabetic Cardiomyopathy by Targeting MyD88 and Inhibiting MyD88‐Dependent Inflammation |
| title_sort | schisandrin b attenuates diabetic cardiomyopathy by targeting myd88 and inhibiting myd88 dependent inflammation |
| topic | cardiomyocytes diabetic cardiomyopathy inflammation MyD88 Schisandrin B |
| url | https://doi.org/10.1002/advs.202202590 |
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