title: The Effects of Puerarin on Rat Ventricular Myocytes and the Potential Mechanism.
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.
authors.affiliation: Laboratory of Molecular Pharmacology, IMM, Peking University, Beijing, 100871, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Xu
authors.affiliation: Laboratory of Innovative Drug Development and Translational Medicine Research of Traditional Chinese Medicine, Chengdu Kanghong Pharmaceutical Limited Company, Chengdu, 610036, China.
authors.forename: Manxi
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Laboratory of Molecular Pharmacology, IMM, Peking University, Beijing, 100871, China.
authors.forename: Shenghui
authors.initials: S
authors.lastname: Liang
authors.affiliation: Laboratory of Innovative Drug Development and Translational Medicine Research of Traditional Chinese Medicine, Chengdu Kanghong Pharmaceutical Limited Company, Chengdu, 610036, China.
authors.forename: Quanshu
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Laboratory of Innovative Drug Development and Translational Medicine Research of Traditional Chinese Medicine, Chengdu Kanghong Pharmaceutical Limited Company, Chengdu, 610036, China.
authors.forename: Yunchuan
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Laboratory of Innovative Drug Development and Translational Medicine Research of Traditional Chinese Medicine, Chengdu Kanghong Pharmaceutical Limited Company, Chengdu, 610036, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Ye
authors.affiliation: Laboratory of Molecular Pharmacology, IMM, Peking University, Beijing, 100871, China.
authors.forename: Qinyi
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Clinical Laboratory, Shaanxi Provincial Hospital of Traditional Chinese Medicine, Xi'an, 710003, China.
authors.forename: Longmei
authors.initials: L
authors.lastname: He
authors.affiliation: Department of Cardiology, Shaanxi Provincial Corps Hospital of Chinese People's Armed Police Forces, Xi'an, 710054, China.
authors.forename: Lanxiang
authors.initials: L
authors.lastname: Ma
authors.affiliation: Department of Cardiology, Shaanxi Provincial Corps Hospital of Chinese People's Armed Police Forces, Xi'an, 710054, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.affiliation: First Department of Surgery, Shaanxi Provincial Corps Hospital of Chinese People's Armed Police Forces, Xi'an, 710054, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: 3rd affiliated hospital of Beijing University, Beijing, 100191, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Laboratory of Innovative Drug Development and Translational Medicine Research of Traditional Chinese Medicine, Chengdu Kanghong Pharmaceutical Limited Company, Chengdu, 610036, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Ke
authors.affiliation: Laboratory of Molecular Pharmacology, IMM, Peking University, Beijing, 100871, China.
authors.forename: Yuchun
authors.initials: Y
authors.lastname: Gu
mesh_terms: D000200:Action Potentials / Q000187:drug effects*; D000244:Adenosine Diphosphate / Q000378:metabolism; D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006352:Heart Ventricles / Q000166:cytology* / Q000187:drug effects*; D007529:Isoflavones / Q000494:pharmacology*; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*; D016276:Ventricular Function / Q000187:drug effects*
chemical_list: D007529:Isoflavones; C490968:Kcnj4 protein, rat; C489461:Kir2.1 channel; D024661:Potassium Channels, Inwardly Rectifying; D014665:Vasodilator Agents; D000244:Adenosine Diphosphate; D017868:Cyclic AMP-Dependent Protein Kinases; C033607:puerarin