Rhodiola Inhibits Atrial Arrhythmogenesis in a Heart Failure Model

J Cardiovasc Electrophysiol. 2016 Sep;27(9):1093-101. doi: 10.1111/jce.13026. Epub 2016 Jul 7.

Abstract

Introduction: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: PI3K/AKT; atrial fibrillation; heart failure; rhodiola.

MeSH terms

  • Action Potentials
  • Animals
  • Anti-Arrhythmia Agents / isolation & purification
  • Anti-Arrhythmia Agents / pharmacology*
  • Atrial Fibrillation / etiology
  • Atrial Fibrillation / metabolism
  • Atrial Fibrillation / physiopathology
  • Atrial Fibrillation / prevention & control*
  • Atrial Function, Left / drug effects
  • Atrial Remodeling / drug effects
  • Calcium Channels, L-Type / genetics
  • Calcium Channels, L-Type / metabolism
  • Collagen / metabolism
  • Disease Models, Animal
  • Fibrosis
  • Heart Atria / drug effects*
  • Heart Atria / metabolism
  • Heart Atria / pathology
  • Heart Atria / physiopathology
  • Heart Failure / complications
  • Heart Failure / drug therapy*
  • Heart Failure / metabolism
  • Heart Failure / physiopathology
  • Heart Rate / drug effects*
  • Phosphatidylinositol 3-Kinase / genetics
  • Phosphatidylinositol 3-Kinase / metabolism
  • Phytotherapy
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Plants, Medicinal
  • Potassium Channels, Voltage-Gated / genetics
  • Potassium Channels, Voltage-Gated / metabolism
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rabbits
  • Rhodiola* / chemistry
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases / genetics
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases / metabolism
  • Signal Transduction / drug effects

Substances

  • Anti-Arrhythmia Agents
  • Calcium Channels, L-Type
  • L-type calcium channel alpha(1C)
  • Plant Extracts
  • Potassium Channels, Voltage-Gated
  • RNA, Messenger
  • Collagen
  • Phosphatidylinositol 3-Kinase
  • Proto-Oncogene Proteins c-akt
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases