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         headline:Rhodiola crenulata reduces ventricular arrhythmia through mitigating the activation of IL-17 and inhibiting the MAPK signaling pathway
         description:Ventricular arrhythmia (VA) is related to inflammatory activity. Rhodiola crenulate (RC) and its main active component, salidroside, have been reported as anti-inflammatory agents. The aim of this study was to demonstrate the effect of RC and salidroside in preventing VA via the inhibition of IL-17 in an ischemic heart failure (HF) model. Rabbit HF models were established by coronary artery ligation for 4 weeks. These rabbits were treated with RC (125, 250, 500 mg/kg) and salidroside (9.5 mg/kg) once every 2 days for 4 weeks. WBC, serum biochemistry, ECG, and the expression of CD4+ T cells were measured every 2 weeks. The mRNA and protein expressions of IL-17 were measured by real time-PCR, ELISA, and Western blotting after RC and salidroside treatment for 4 weeks. Open-chest epicardial catheter stimulation was performed for VA provocation. After RC and salidroside treatment in HF left ventricle, (1) the levels of WBC and CD4+ T cells decreased, (2) the expression of IL-17 and its downstream target genes, IL-6, TNF-α, IL-1β, IL-8, and CCL20, reduced, (3) the level of NLRP3 inflammasome was decreased, (4) fibrosis and collagen production were significantly downregulated, (5) p38 MAPK and ERK1/2 phosphorylation were attenuated, (6) the inducibility of VA was decreased, and (7) the levels of Kir2.1, Nav1.5, NCX, PLB, SERCA2a and RyR were up-regulated. RC inhibited the expression of IL-17 and its downstream target genes that were mediated by activation of several MAPKs, which decreased the levels of fibrosis and apoptosis and suppressed VA.
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            name:Taipei Veterans General Hospital
            address:
               name:Heart Rhythm Center and Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
               type:PostalAddress
            type:Organization
            name:National Yang-Ming University School of Medicine
            address:
               name:Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
               type:PostalAddress
            type:Organization
      name:Li-Wei Lo
      affiliation:
            name:Taipei Veterans General Hospital
            address:
               name:Heart Rhythm Center and Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
               type:PostalAddress
            type:Organization
            name:National Yang-Ming University School of Medicine
            address:
               name:Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
               type:PostalAddress
            type:Organization
      name:Yu-Feng Hu
      affiliation:
            name:Taipei Veterans General Hospital
            address:
               name:Heart Rhythm Center and Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
               type:PostalAddress
            type:Organization
            name:National Yang-Ming University School of Medicine
            address:
               name:Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
               type:PostalAddress
            type:Organization
      name:Fa-Po Chung
      affiliation:
            name:Taipei Veterans General Hospital
            address:
               name:Heart Rhythm Center and Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
               type:PostalAddress
            type:Organization
            name:National Yang-Ming University School of Medicine
            address:
               name:Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
               type:PostalAddress
            type:Organization
      name:Shien-Fong Lin
      affiliation:
            name:National Chiao Tung University
            address:
               name:Institute of Biomedical Engineering, National Chiao Tung University, Hsinchu, Taiwan
               type:PostalAddress
            type:Organization
      name:Shih-Lin Chang
      url:http://orcid.org/0000-0001-7030-8471
      affiliation:
            name:Taipei Veterans General Hospital
            address:
               name:Heart Rhythm Center and Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
               type:PostalAddress
            type:Organization
            name:National Yang-Ming University School of Medicine
            address:
               name:Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Satoshi Higa
      affiliation:
            name:Makiminato Central Hospital
            address:
               name:Cardiac Electrophysiology and Pacing Laboratory, Division of Cardiovascular Medicine, Makiminato Central Hospital, Okinawa, Japan
               type:PostalAddress
            type:Organization
      name:Shih-Ann Chen
      affiliation:
            name:Taipei Veterans General Hospital
            address:
               name:Heart Rhythm Center and Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
               type:PostalAddress
            type:Organization
            name:National Yang-Ming University School of Medicine
            address:
               name:Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
               type:PostalAddress
            type:Organization
PostalAddress:
      name:Heart Rhythm Center and Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
      name:Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan
      name:Heart Rhythm Center and Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
      name:Shuang-Ho Hospital, Taipei Medical University, Taipei, Taiwan
      name:Heart Rhythm Center and Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
      name:Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
      name:Heart Rhythm Center and Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
      name:Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
      name:Heart Rhythm Center and Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
      name:Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
      name:Heart Rhythm Center and Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
      name:Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
      name:Institute of Biomedical Engineering, National Chiao Tung University, Hsinchu, Taiwan
      name:Heart Rhythm Center and Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
      name:Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
      name:Cardiac Electrophysiology and Pacing Laboratory, Division of Cardiovascular Medicine, Makiminato Central Hospital, Okinawa, Japan
      name:Heart Rhythm Center and Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
      name:Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
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