Effects of Mixed Herbal Extracts from Parched Puerariae Radix, Gingered Magnoliae Cortex, Glycyrrhizae Radix and Euphorbiae Radix (KIOM-79) on Cardiac Ion Channels and Action Potentials.
10.3346/jkms.2009.24.3.403
- Author:
Su Jung PARK
1
;
Kwan Seok CHOI
;
Dong Hoon SHIN
;
Jin Sook KIM
;
Dae Sik JANG
;
Jae Beom YOUM
;
Han CHOE
;
Yung E EARM
;
Sung Joon KIM
Author Information
1. Department of Physiology, Seoul National University College of Medicine, Seoul, Korea. sjoonkim@snu.ac.kr
- Publication Type:Original Article
- Keywords:
Heart;
Action Potentials;
Long-QT Syndrome;
Herbal Extract;
Ion Channels;
hERG
- MeSH:
Action Potentials/*drug effects;
Animals;
Cell Line;
Computer Simulation;
Female;
Ginger/chemistry;
Humans;
Ion Channels/*physiology;
Long QT Syndrome/diagnosis;
Male;
Membrane Potentials/drug effects/physiology;
Myocytes, Cardiac/*drug effects/physiology;
Patch-Clamp Techniques;
Plant Extracts/*pharmacology;
Pueraria/chemistry;
Purkinje Fibers/drug effects/physiology;
Rabbits;
Rats;
Rats, Sprague-Dawley
- From:Journal of Korean Medical Science
2009;24(3):403-412
- CountryRepublic of Korea
- Language:English
-
Abstract:
KIOM-79, a mixture of ethanol extracts from four herbs (parched Puerariae radix, gingered Magnoliae cortex, Glycyrrhizae radix and Euphorbiae radix), has been developed for the potential therapeutic application to diabetic symptoms. Because screening of unexpected cardiac arrhythmia is compulsory for the new drug development, we investigated the effects of KIOM-79 on the action potential (AP) and various ion channel currents in cardiac myocytes. KIOM-79 decreased the upstroke velocity (Vmax) and plateau potential while slightly increased the duration of action potential (APD). Consistent with the decreased Vmax and plateau potential, the peak amplitude of Na+ current (INa) and Ca2+ current (ICa,L) were decreased by KIOM-79. KIOM-79 showed dual effects on hERG K+ current; increase of depolarization phase current (Idepol) and decreased tail current at repolarization phase (Itail). The increase of APD was suspected due to the decreased Itail. In computer simulation, the change of cardiac action potential could be well simulated based on the effects of KIOM-79 on various membrane currents. As a whole, the influence of KIOM-79 on cardiac ion channels are minor at concentrations effective for the diabetic models (0.1-10 microg/mL). The results suggest safety in terms of the risk of cardiac arrhythmia. Also, our study demonstrates the usefulness of the cardiac computer simulation in screening drug-induced long-QT syndrome.
