The Effects of Puerarin on Rat Ventricular Myocytes and the Potential Mechanism

Hao Xu, Manxi Zhao, Shenghui Liang, Quanshu Huang, Yunchuan Xiao, Liang Ye, Qinyi Wang, Longmei He, Lanxiang Ma, Hua Zhang, Li Zhang, Hui Jiang, Xiao Ke, Yuchun Gu

Research output: Contribution to journalArticle

Abstract

Puerarin, a known isoflavone, is commonly found as a Chinese herb medicine. It is widely used in China to treat cardiac diseases such as angina, cardiac infarction and arrhythmia. However, its cardioprotective mechanism remains unclear. In this study, puerarin significantly prolonged ventricular action potential duration (APD) with a dosage dependent manner in the micromolar range on isolated rat ventricular myocytes. However, submicromolar puerarin had no effect on resting membrane potential (RMP), action potential amplitude (APA) and maximal velocity of depolarization (Vmax) of action potential. Only above the concentration of 10 mM, puerarin exhibited more aggressive effect on action potential, and shifted RMP to the positive direction. Millimolar concentrations of puerarin significantly inhibited inward rectified K+ channels in a dosage dependent manner, and exhibited bigger effects upon Kir2.1 vs Kir2.3 in transfected HEK293 cells. As low as micromolar range concentrations of puerarin significantly inhibited Kv7.1 and IKs. These inhibitory effects may due to the direct inhibition of puerarin upon channels not via the PKA-dependent pathway. These results provided direct preclinical evidence that puerarin prolonged APD via its inhibitory effect upon Kv7.1 and IKs, contributing to a better understanding the mechanism of puerarin cardioprotection in the treatment of cardiovascular diseases.
Original languageEnglish
Article number35475
JournalScientific Reports
Volume6
Issue number4
Early online date20 Oct 2016
DOIs
Publication statusPublished - 20 Oct 2016

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Muscle Cells
Action Potentials
Membrane Potentials
puerarin
Isoflavones
HEK293 Cells
Infarction
Cardiac Arrhythmias
Heart Diseases
China
Cardiovascular Diseases
Medicine

Bibliographical note

© The Author(s) 2016. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

Funding: 973 Project No. 2013 CB531206, 973 Project No. 2012 CB517803 and No. 81170236, No. 31127001 and No. 31221002.

Keywords

  • Ventricular tachycardia

Cite this

Xu, Hao ; Zhao, Manxi ; Liang, Shenghui ; Huang, Quanshu ; Xiao, Yunchuan ; Ye, Liang ; Wang, Qinyi ; He, Longmei ; Ma, Lanxiang ; Zhang, Hua ; Zhang, Li ; Jiang, Hui ; Ke, Xiao ; Gu, Yuchun. / The Effects of Puerarin on Rat Ventricular Myocytes and the Potential Mechanism. In: Scientific Reports. 2016 ; Vol. 6, No. 4.
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Xu, H, Zhao, M, Liang, S, Huang, Q, Xiao, Y, Ye, L, Wang, Q, He, L, Ma, L, Zhang, H, Zhang, L, Jiang, H, Ke, X & Gu, Y 2016, 'The Effects of Puerarin on Rat Ventricular Myocytes and the Potential Mechanism', Scientific Reports, vol. 6, no. 4, 35475 . https://doi.org/10.1038/srep35475

The Effects of Puerarin on Rat Ventricular Myocytes and the Potential Mechanism. / Xu, Hao; Zhao, Manxi; Liang, Shenghui; Huang, Quanshu; Xiao, Yunchuan; Ye, Liang; Wang, Qinyi; He, Longmei; Ma, Lanxiang; Zhang, Hua; Zhang, Li; Jiang, Hui; Ke, Xiao; Gu, Yuchun.

In: Scientific Reports, Vol. 6, No. 4, 35475 , 20.10.2016.

Research output: Contribution to journalArticle

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AU - Xu, Hao

AU - Zhao, Manxi

AU - Liang, Shenghui

AU - Huang, Quanshu

AU - Xiao, Yunchuan

AU - Ye, Liang

AU - Wang, Qinyi

AU - He, Longmei

AU - Ma, Lanxiang

AU - Zhang, Hua

AU - Zhang, Li

AU - Jiang, Hui

AU - Ke, Xiao

AU - Gu, Yuchun

N1 - © The Author(s) 2016. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. Funding: 973 Project No. 2013 CB531206, 973 Project No. 2012 CB517803 and No. 81170236, No. 31127001 and No. 31221002.

PY - 2016/10/20

Y1 - 2016/10/20

N2 - Puerarin, a known isoflavone, is commonly found as a Chinese herb medicine. It is widely used in China to treat cardiac diseases such as angina, cardiac infarction and arrhythmia. However, its cardioprotective mechanism remains unclear. In this study, puerarin significantly prolonged ventricular action potential duration (APD) with a dosage dependent manner in the micromolar range on isolated rat ventricular myocytes. However, submicromolar puerarin had no effect on resting membrane potential (RMP), action potential amplitude (APA) and maximal velocity of depolarization (Vmax) of action potential. Only above the concentration of 10 mM, puerarin exhibited more aggressive effect on action potential, and shifted RMP to the positive direction. Millimolar concentrations of puerarin significantly inhibited inward rectified K+ channels in a dosage dependent manner, and exhibited bigger effects upon Kir2.1 vs Kir2.3 in transfected HEK293 cells. As low as micromolar range concentrations of puerarin significantly inhibited Kv7.1 and IKs. These inhibitory effects may due to the direct inhibition of puerarin upon channels not via the PKA-dependent pathway. These results provided direct preclinical evidence that puerarin prolonged APD via its inhibitory effect upon Kv7.1 and IKs, contributing to a better understanding the mechanism of puerarin cardioprotection in the treatment of cardiovascular diseases.

AB - Puerarin, a known isoflavone, is commonly found as a Chinese herb medicine. It is widely used in China to treat cardiac diseases such as angina, cardiac infarction and arrhythmia. However, its cardioprotective mechanism remains unclear. In this study, puerarin significantly prolonged ventricular action potential duration (APD) with a dosage dependent manner in the micromolar range on isolated rat ventricular myocytes. However, submicromolar puerarin had no effect on resting membrane potential (RMP), action potential amplitude (APA) and maximal velocity of depolarization (Vmax) of action potential. Only above the concentration of 10 mM, puerarin exhibited more aggressive effect on action potential, and shifted RMP to the positive direction. Millimolar concentrations of puerarin significantly inhibited inward rectified K+ channels in a dosage dependent manner, and exhibited bigger effects upon Kir2.1 vs Kir2.3 in transfected HEK293 cells. As low as micromolar range concentrations of puerarin significantly inhibited Kv7.1 and IKs. These inhibitory effects may due to the direct inhibition of puerarin upon channels not via the PKA-dependent pathway. These results provided direct preclinical evidence that puerarin prolonged APD via its inhibitory effect upon Kv7.1 and IKs, contributing to a better understanding the mechanism of puerarin cardioprotection in the treatment of cardiovascular diseases.

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