title: 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.
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 (V(max)) and plateau potential while slightly increased the duration of action potential (APD). Consistent with the decreased V(max) and plateau potential, the peak amplitude of Na+ current (I(Na)) and Ca2+ current (I(Ca,L)) were decreased by KIOM-79. KIOM-79 showed dual effects on hERG K+ current; increase of depolarization phase current (I(depol)) and decreased tail current at repolarization phase (I(tail)). The increase of APD was suspected due to the decreased I(tail). 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.
authors: Department of Physiology, Seoul National University College of Medicine, Seoul, Korea.
authors: Su Jung
authors: SJ
authors: Park
authors: Kwan Seok
authors: KS
authors: Choi
authors: Dong Hoon
authors: DH
authors: Shin
authors: Jin Sook
authors: JS
authors: Kim
authors: Dae Sik
authors: DS
authors: Jang
authors: Jae Beom
authors: JB
authors: Youm
authors: Han
authors: H
authors: Choe
authors: Yung E
authors: YE
authors: Earm
authors: Sung Joon
authors: SJ
authors: Kim
mesh_terms: D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D002460:Cell Line; D003198:Computer Simulation; D005260:Female; D020939:Zingiber officinale / Q000737:chemistry; D006801:Humans; D007473:Ion Channels / Q000502:physiology*; D008133:Long QT Syndrome / Q000175:diagnosis; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D010936:Plant Extracts / Q000494:pharmacology*; D029908:Pueraria / Q000737:chemistry; D011690:Purkinje Fibers / Q000187:drug effects / Q000502:physiology; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D007473:Ion Channels; C517978:KIOM 79; D010936:Plant Extracts