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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.

Park SJ, Choi KS, Shin DH, Kim JS, Jang DS, Youm JB, Choe H, Earm YE, Kim SJ - J. Korean Med. Sci. (2009)

Bottom Line: 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).

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Seoul National University College of Medicine, Seoul, Korea.

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.

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Related in: MedlinePlus

Effect of KIOM-79 on the APs in rabbit cardiac purkinje fibers. (A) Representative recording of triggered APs in control and in the presence of 10 µg/mL KIOM-79 (red trace). (B) Bar graphs showing shortened total amplitude (TA) and rate of maximum depolarization at phase 0 (Vmax) in the presence of 10 µg/mL KIOM-79 (upper panel). APD90 was increased by KIOM-79 (10 µg/mL) while APD50 was not affected (lower panels). *P value <0.05.
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Figure 1: Effect of KIOM-79 on the APs in rabbit cardiac purkinje fibers. (A) Representative recording of triggered APs in control and in the presence of 10 µg/mL KIOM-79 (red trace). (B) Bar graphs showing shortened total amplitude (TA) and rate of maximum depolarization at phase 0 (Vmax) in the presence of 10 µg/mL KIOM-79 (upper panel). APD90 was increased by KIOM-79 (10 µg/mL) while APD50 was not affected (lower panels). *P value <0.05.

Mentions: The representative trace of membrane potential showed that an application of 10 µg/mL of KIOM-79 increased the action potential duration (APD) and slightly decreased the amplitude of AP (Fig. 1A). The effects of KIOM-79 on APD were quantified in terms of APD90 and APD50. Also, we measured the Vmax and TA (see Materials and methods). The summarized results from three rabbits showed that TA and Vmax were decreased by 10 µg/mL of KIOM-79. The APD90 was increased by KIOM-79 while APD50 was not affected (Fig. 1B). The resting membrane potential (RMP) was not significantly changed by KIOM-79.


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.

Park SJ, Choi KS, Shin DH, Kim JS, Jang DS, Youm JB, Choe H, Earm YE, Kim SJ - J. Korean Med. Sci. (2009)

Effect of KIOM-79 on the APs in rabbit cardiac purkinje fibers. (A) Representative recording of triggered APs in control and in the presence of 10 µg/mL KIOM-79 (red trace). (B) Bar graphs showing shortened total amplitude (TA) and rate of maximum depolarization at phase 0 (Vmax) in the presence of 10 µg/mL KIOM-79 (upper panel). APD90 was increased by KIOM-79 (10 µg/mL) while APD50 was not affected (lower panels). *P value <0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2698184&req=5

Figure 1: Effect of KIOM-79 on the APs in rabbit cardiac purkinje fibers. (A) Representative recording of triggered APs in control and in the presence of 10 µg/mL KIOM-79 (red trace). (B) Bar graphs showing shortened total amplitude (TA) and rate of maximum depolarization at phase 0 (Vmax) in the presence of 10 µg/mL KIOM-79 (upper panel). APD90 was increased by KIOM-79 (10 µg/mL) while APD50 was not affected (lower panels). *P value <0.05.
Mentions: The representative trace of membrane potential showed that an application of 10 µg/mL of KIOM-79 increased the action potential duration (APD) and slightly decreased the amplitude of AP (Fig. 1A). The effects of KIOM-79 on APD were quantified in terms of APD90 and APD50. Also, we measured the Vmax and TA (see Materials and methods). The summarized results from three rabbits showed that TA and Vmax were decreased by 10 µg/mL of KIOM-79. The APD90 was increased by KIOM-79 while APD50 was not affected (Fig. 1B). The resting membrane potential (RMP) was not significantly changed by KIOM-79.

Bottom Line: 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).

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Seoul National University College of Medicine, Seoul, Korea.

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.

Show MeSH
Related in: MedlinePlus