title: Rhodiola Inhibits Atrial Arrhythmogenesis in a Heart Failure Model.
abstract: Rhodiola, a popular plant in Tibet, has been proven to decrease arrhythmia. The aim of this study was to elucidate the molecular mechanism and electrophysiological properties of rhodiola in the suppression of atrial fibrillation.
  
  
  
  This study consisted of 3 groups as follows: Group 1: normal control rabbits (n = 5); Group 2: rabbits with heart failure (HF) created by coronary ligation and who received 2 weeks of water orally as a placebo (n = 5); and Group 3: rabbits with HF who received 2 weeks of a rhodiola 270 mg/kg/day treatment orally (n = 5). The monophasic action potential, histology, and real-time polymerase chain reaction (RT-PCR) analysis of ionic channels and PI3K/AKT/eNOS were examined.
  
  
  
  Compared with the HF group, attenuated atrial fibrosis (35.4 ± 17.4% vs. 16.9 ± 8.4%, P = 0.05) and improved left ventricular (LV) ejection fraction (51.6 ± 3.4% vs. 68.0 ± 0.5%, P = 0.001) were observed in the rhodiola group. The rhodiola group had a shorter ERP (85.3 ± 6.8 vs. 94.3 ± 1.2, P = 0.002), APD90 (89.3 ± 1.5 vs. 112.7 ± 0.7, P < 0.001) in the left atrium (LA), and decreased AF inducibility (0.90 ± 0.04 vs. 0.42 ± 0.04, P < 0.001) compared with the HF group. The mRNA expressions of Kv1.4, Kv1.5, Kv4.3, KvLQT1, Cav1.2, and SERCA2a in the HF LA were up-regulated after rhodiola treatment. The rhodiola-treated HF LA demonstrated higher mRNA expression of PI3K-AKT compared with the HF group.
  
  
  
  Rhodiola reversed LA electrical remodeling, attenuated atrial fibrosis and suppressed AF in rabbits with HF. The beneficial electrophysiological effect of rhodiola may be related to upregulation of Kv1.4, Kv1.5, Kv4.3, KvLQT1, Cav1.2, SERCA2a, and activation of PI3K/AKT signaling.
authors.affiliation: Division of Cardiology, Department of Medicine, Shuang-Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.
authors.forename: Shuen-Hsin
authors.initials: SH
authors.lastname: Liu
authors.affiliation: Division of Cardiology, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Ya-Wen
authors.initials: YW
authors.lastname: Hsiao
authors.affiliation: Division of Cardiology, Department of Medicine, Alexandra Hospital, Jurong Health, Singapore.
authors.forename: Eric
authors.initials: E
authors.lastname: Chong
authors.affiliation: Department of Electrophysiology and Cardiac Pacing, Heart and General Hospital, India.
authors.forename: Rahul
authors.initials: R
authors.lastname: Singhal
authors.affiliation: Division of Cardiovascular Medicine, Cheng Hsin General Hospital, Taipei, Taiwan.
authors.forename: Man-Cai
authors.initials: MC
authors.lastname: Fong
authors.affiliation: Division of Cardiology, Taipei Veterans General Hospital, Taipei, Taiwan.|Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.
authors.forename: Yung-Nan
authors.initials: YN
authors.lastname: Tsai
authors.affiliation: Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.|Division of Cardiovascular Surgery, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Chiao-Po
authors.initials: CP
authors.lastname: Hsu
authors.affiliation: Department of Biomedical Engineering, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Yao-Chang
authors.initials: YC
authors.lastname: Chen
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.|Division of Cardiovascular Medicine, Department of Internal Medicine, Wan-Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yi-Jen
authors.initials: YJ
authors.lastname: Chen
authors.affiliation: Division of Cardiology, Taipei Veterans General Hospital, Taipei, Taiwan.|Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.
authors.forename: Chuen-Wang
authors.initials: CW
authors.lastname: Chiou
authors.affiliation: Division of Cardiology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Shuo-Ju
authors.initials: SJ
authors.lastname: Chiang
authors.affiliation: Division of Cardiology, Taipei Veterans General Hospital, Taipei, Taiwan. ep.slchang@msa.hinet.net.|Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan. ep.slchang@msa.hinet.net.
authors.forename: Shih-Lin
authors.initials: SL
authors.lastname: Chang
authors.affiliation: Division of Cardiology, Taipei Veterans General Hospital, Taipei, Taiwan.|Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.
authors.forename: Shih-Ann
authors.initials: SA
authors.lastname: Chen
mesh_terms: D000200:Action Potentials; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000302:isolation & purification / Q000494:pharmacology*; D001281:Atrial Fibrillation / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D016279:Atrial Function, Left / Q000187:drug effects; D064752:Atrial Remodeling / Q000187:drug effects; D020746:Calcium Channels, L-Type / Q000235:genetics / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D005355:Fibrosis; D006325:Heart Atria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006333:Heart Failure / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects*; D058539:Phosphatidylinositol 3-Kinase / Q000235:genetics / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D029771:Rhodiola / Q000737:chemistry; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000889:Anti-Arrhythmia Agents; D020746:Calcium Channels, L-Type; C419385:L-type calcium channel alpha(1C); D010936:Plant Extracts; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger; D003094:Collagen; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases
keywords: PI3K/AKT; atrial fibrillation; heart failure; rhodiola