PMID- 23196428
OWN - NLM
STAT- MEDLINE
DCOM- 20130805
LR  - 20190720
IS  - 1347-5215 (Electronic)
IS  - 0918-6158 (Linking)
VI  - 36
IP  - 2
DP  - 2013
TI  - Potential antiarrhythmic effect of methyl 3,4,5-trimethoxycinnamate, a bioactive 
      substance from roots of polygalae radix: suppression of triggered activities in 
      rabbit myocytes.
PG  - 238-44
AB  - 3,4,5-Trimethoxycinnamic acid (TMCA), methyl 3,4,5-trimethoxycinnamate (M-TMCA) 
      and p-methoxycinnamic acid (PMCA) have been identified as the major bioactive 
      components in the serum collected from rats treated with oral administration of 
      Polygalae Radix ("YuanZhi," the roots of Polygala tenuifolia WILLD.), a 
      traditional Chinese medicine used to relieve insomnia, anxiety and heart 
      palpitation. The present study was designed to investigate its direct 
      electrophysiological effects on isolated ventricular myocytes from rabbits. 
      Whole-cell configuration of the patch-clamp technique was used to measure action 
      potential (AP) and membrane currents in single ventricular myocytes enzymatically 
      isolated from adult rabbit hearts. Ca(2+) transients were recorded in myocytes 
      loaded with the Ca(2+) indicator Fluo-4AM. Among three bioactive substances of 
      Polygala metabolites, only M-TMCA (15-30 microM) significantly shortened action 
      potential duration at 50% and 90% repolarization (APD(50) and APD(90)) in 
      cardiomyocytes in a concentration-dependent and a reversible manner. M-TMCA also 
      inhibited L-type calcium current (I(Ca,L)), but showed effect on neither 
      transient outward potassium current (I(to)) nor steady-state potassium current 
      (I(K,SS)). Furthermore, M-TMCA abolished isoprenaline plus BayK8644-induced early 
      afterdepolarizations (EADs) and suppressed delayed afterdepolarizations (DADs) 
      and triggered activities (TAs). This potential anti-arrhythmic effects were 
      likely attributed by the inhibition of I(Ca,L) and the suppression of 
      intracellular Ca(2+) transients, which consequently suppress the generation of 
      transient inward current (I(ti)). These findings suggest that M-TMCA may protect 
      the heart from arrhythmias via its inhibitory effect on calcium channel.
FAU - Zhao, Zhenghang
AU  - Zhao Z
AD  - Department of Pharmacology, School of Medicine, Xi'an Jiaotong University, Xi'an 
      710061, China. zzh@mail.xjtu.edu.cn
FAU - Fang, Minfeng
AU  - Fang M
FAU - Xiao, Dandan
AU  - Xiao D
FAU - Liu, Mei
AU  - Liu M
FAU - Fefelova, Nadezhda
AU  - Fefelova N
FAU - Huang, Chen
AU  - Huang C
FAU - Zang, Wei-Jin
AU  - Zang WJ
FAU - Xie, Lai-Hua
AU  - Xie LH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121129
PL  - Japan
TA  - Biol Pharm Bull
JT  - Biological & pharmaceutical bulletin
JID - 9311984
RN  - 0 (Anti-Arrhythmia Agents)
RN  - 0 (Cinnamates)
RN  - 0 (Drugs, Chinese Herbal)
RN  - C9096D920O (3,4,5-trimethoxycinnamic acid)
SB  - IM
MH  - Animals
MH  - Anti-Arrhythmia Agents/*pharmacology
MH  - Cinnamates/*pharmacology
MH  - Drugs, Chinese Herbal/pharmacology
MH  - Male
MH  - Myocytes, Cardiac/*drug effects/physiology
MH  - Plant Roots
MH  - *Polygala
MH  - Rabbits
EDAT- 2012/12/01 06:00
MHDA- 2013/08/06 06:00
CRDT- 2012/12/01 06:00
PHST- 2012/12/01 06:00 [entrez]
PHST- 2012/12/01 06:00 [pubmed]
PHST- 2013/08/06 06:00 [medline]
AID - DN/JST.JSTAGE/bpb/b12-00654 [pii]
AID - 10.1248/bpb.b12-00654 [doi]
PST - ppublish
SO  - Biol Pharm Bull. 2013;36(2):238-44. doi: 10.1248/bpb.b12-00654. Epub 2012 Nov 29.