Dual Activity of Ginsenoside Rb1 in Hypertrophic Cardiomyocytes and Activated Macrophages: Implications for the Therapeutic Intervention of Cardiac Hypertrophy
Shihua Wang,1 Yimeng Cui,1 Minqi Xiong,1,2 Mei Li,1 Peiwei Wang,1,2 Jingang Cui,1,2 Xiaoye Du,1,2 Yu Chen,1– 3 Teng Zhang1,2 1Yueyang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Clinical Research Institute of Integrative M...
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Dove Medical Press
2021
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oai:doaj.org-article:5722a4daec65464ea7017676c8e7fa742021-12-02T15:33:24ZDual Activity of Ginsenoside Rb1 in Hypertrophic Cardiomyocytes and Activated Macrophages: Implications for the Therapeutic Intervention of Cardiac Hypertrophy1178-7031https://doaj.org/article/5722a4daec65464ea7017676c8e7fa742021-05-01T00:00:00Zhttps://www.dovepress.com/dual-activity-of-ginsenoside-rb1-in-hypertrophic-cardiomyocytes-and-ac-peer-reviewed-fulltext-article-JIRhttps://doaj.org/toc/1178-7031Shihua Wang,1 Yimeng Cui,1 Minqi Xiong,1,2 Mei Li,1 Peiwei Wang,1,2 Jingang Cui,1,2 Xiaoye Du,1,2 Yu Chen,1– 3 Teng Zhang1,2 1Yueyang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Clinical Research Institute of Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3Laboratory of Clinical and Molecular Pharmacology, Yueyang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Teng Zhang; Yu ChenShanghai University of Traditional Chinese Medicine, 110 Ganhe Rd, Shanghai, 200437, ChinaTel +86-21-55982301; +86-21-55982302Email zhangteng2089@shutcm.edu.cn; chenyu@shutcm.edu.cnPurpose: Owing to the important mechanistic implications in the pathogenesis of cardiac hypertrophy and heart failure, inflammation has been proposed as a druggable target for the treatment of cardiac hypertrophy and heart failure. Ginseng is a widely used medicinal herb for the treatment of cardiovascular disorders. As one of the major chemical components of ginseng, ginsenoside Rb1 (Rb1) contributes to the cardiovascular effects of ginseng. Meanwhile, anti-inflammatory activity of Rb1 has also been documented. The current work aims to further delineate the pharmacological implications of Rb1 in the treatment of cardiac hypertrophy.Methods: Angiotensin II (Ang II) infusion mouse model was adopted to investigate the effects of Rb1 on cardiac hypertrophic remodeling and associated inflammation in vivo. Furthermore, the mechanisms of actions of Rb1 in modulating the hypertrophic and inflammatory responses were investigated in cardiomyocytes and macrophages, respectively.Results: Rb1 mitigates Ang II–induced cardiac hypertrophy, cardiac inflammation and systemic inflammation in vivo. In cardiomyocytes, Rb1 directly counteracts the pro-hypertrophic effects of Ang II and phenylephrine and maintains the mitochondrial function. In lipopolysaccharide (LPS)-stimulated macrophages, Rb1 decreases the phosphorylation of mitogen-activated protein kinases (MAPKs) and mitogen-activated protein kinase kinase 1/2 (MEK1/2) and reduces the production of inflammation mediators such as interleukin (IL)-1 beta, IL-6 and tumor necrosis factor (TNF). Rb1 also suppresses the expression of pro-hypertrophic microRNA-155 (miR-155) in LPS- or Ang II-stimulated macrophages. Furthermore, in activated macrophages, miR-155 is in part accountable for the suppressive effect of Rb1 on the production of IL-6, an inflammation mediator with pro-hypertrophic functions in the heart.Conclusion: The work here provides novel experimental evidence supporting the notion that Rb1 protects against cardiac hypertrophy in part through suppressing the inflammatory mechanisms that promotes the pathological remodeling of the heart.Keywords: angiotensin II, inflammation, interleukin 6Wang SCui YXiong MLi MWang PCui JDu XChen YZhang TDove Medical Pressarticleangiotensin iiinflammationinterleukin 6PathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 14, Pp 1789-1806 (2021) |
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angiotensin ii inflammation interleukin 6 Pathology RB1-214 Therapeutics. Pharmacology RM1-950 |
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angiotensin ii inflammation interleukin 6 Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Wang S Cui Y Xiong M Li M Wang P Cui J Du X Chen Y Zhang T Dual Activity of Ginsenoside Rb1 in Hypertrophic Cardiomyocytes and Activated Macrophages: Implications for the Therapeutic Intervention of Cardiac Hypertrophy |
| description |
Shihua Wang,1 Yimeng Cui,1 Minqi Xiong,1,2 Mei Li,1 Peiwei Wang,1,2 Jingang Cui,1,2 Xiaoye Du,1,2 Yu Chen,1– 3 Teng Zhang1,2 1Yueyang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Clinical Research Institute of Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3Laboratory of Clinical and Molecular Pharmacology, Yueyang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Teng Zhang; Yu ChenShanghai University of Traditional Chinese Medicine, 110 Ganhe Rd, Shanghai, 200437, ChinaTel +86-21-55982301; +86-21-55982302Email zhangteng2089@shutcm.edu.cn; chenyu@shutcm.edu.cnPurpose: Owing to the important mechanistic implications in the pathogenesis of cardiac hypertrophy and heart failure, inflammation has been proposed as a druggable target for the treatment of cardiac hypertrophy and heart failure. Ginseng is a widely used medicinal herb for the treatment of cardiovascular disorders. As one of the major chemical components of ginseng, ginsenoside Rb1 (Rb1) contributes to the cardiovascular effects of ginseng. Meanwhile, anti-inflammatory activity of Rb1 has also been documented. The current work aims to further delineate the pharmacological implications of Rb1 in the treatment of cardiac hypertrophy.Methods: Angiotensin II (Ang II) infusion mouse model was adopted to investigate the effects of Rb1 on cardiac hypertrophic remodeling and associated inflammation in vivo. Furthermore, the mechanisms of actions of Rb1 in modulating the hypertrophic and inflammatory responses were investigated in cardiomyocytes and macrophages, respectively.Results: Rb1 mitigates Ang II–induced cardiac hypertrophy, cardiac inflammation and systemic inflammation in vivo. In cardiomyocytes, Rb1 directly counteracts the pro-hypertrophic effects of Ang II and phenylephrine and maintains the mitochondrial function. In lipopolysaccharide (LPS)-stimulated macrophages, Rb1 decreases the phosphorylation of mitogen-activated protein kinases (MAPKs) and mitogen-activated protein kinase kinase 1/2 (MEK1/2) and reduces the production of inflammation mediators such as interleukin (IL)-1 beta, IL-6 and tumor necrosis factor (TNF). Rb1 also suppresses the expression of pro-hypertrophic microRNA-155 (miR-155) in LPS- or Ang II-stimulated macrophages. Furthermore, in activated macrophages, miR-155 is in part accountable for the suppressive effect of Rb1 on the production of IL-6, an inflammation mediator with pro-hypertrophic functions in the heart.Conclusion: The work here provides novel experimental evidence supporting the notion that Rb1 protects against cardiac hypertrophy in part through suppressing the inflammatory mechanisms that promotes the pathological remodeling of the heart.Keywords: angiotensin II, inflammation, interleukin 6 |
| format |
article |
| author |
Wang S Cui Y Xiong M Li M Wang P Cui J Du X Chen Y Zhang T |
| author_facet |
Wang S Cui Y Xiong M Li M Wang P Cui J Du X Chen Y Zhang T |
| author_sort |
Wang S |
| title |
Dual Activity of Ginsenoside Rb1 in Hypertrophic Cardiomyocytes and Activated Macrophages: Implications for the Therapeutic Intervention of Cardiac Hypertrophy |
| title_short |
Dual Activity of Ginsenoside Rb1 in Hypertrophic Cardiomyocytes and Activated Macrophages: Implications for the Therapeutic Intervention of Cardiac Hypertrophy |
| title_full |
Dual Activity of Ginsenoside Rb1 in Hypertrophic Cardiomyocytes and Activated Macrophages: Implications for the Therapeutic Intervention of Cardiac Hypertrophy |
| title_fullStr |
Dual Activity of Ginsenoside Rb1 in Hypertrophic Cardiomyocytes and Activated Macrophages: Implications for the Therapeutic Intervention of Cardiac Hypertrophy |
| title_full_unstemmed |
Dual Activity of Ginsenoside Rb1 in Hypertrophic Cardiomyocytes and Activated Macrophages: Implications for the Therapeutic Intervention of Cardiac Hypertrophy |
| title_sort |
dual activity of ginsenoside rb1 in hypertrophic cardiomyocytes and activated macrophages: implications for the therapeutic intervention of cardiac hypertrophy |
| publisher |
Dove Medical Press |
| publishDate |
2021 |
| url |
https://doaj.org/article/5722a4daec65464ea7017676c8e7fa74 |
| work_keys_str_mv |
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