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FASEB J. 2018 Mar;32(3):1440-1451. doi: 10.1096/fj.201700494RR. Epub 2018 Jan 3.

Effects of hawthorn ( Crataegus pentagyna) leaf extract on electrophysiologic properties of cardiomyocytes derived from human cardiac arrhythmia-specific induced pluripotent stem cells.

Author information

1
Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, Academic Center for Education, Culture, and Research, Tehran, Iran.
2
Department of Horticultural Science, Tarbiat Modares University (TMU), Tehran, Iran.
3
Department of Horticultural Sciences, Faculty of Agriculture, Urmia University, Urmia, Iran.
4
Center for Physiology and Pathophysiology, Institute for Neurophysiology, Medical Faculty, University of Cologne, Cologne, Germany.
5
Department of Developmental Biology, University of Science and Culture, Tehran, Iran.

Abstract

Cardiac arrhythmias are major life-threatening conditions. The landmark discovery of induced pluripotent stem cells has provided a promising in vitro system for modeling hereditary cardiac arrhythmias as well as drug development and toxicity testing. Nowadays, nutraceuticals are frequently used as supplements for cardiovascular therapy. Here we studied the cardiac effects of hawthorn ( Crataegus pentagyna) leaf extract using cardiomyocytes (CMs) differentiated from healthy human embryonic stem cells, long QT syndrome type 2 (LQTS2), and catecholaminergic polymorphic ventricular tachycardia type 1 (CPVT1) patient-specific induced pluripotent stem cells. The hydroalcoholic extract resulted in a dose-dependent negative chronotropic effect in all CM preparations leading to a significant reduction at 1000 µg/ml. This was accompanied by prolongation of field potential durations, although with different magnitudes in CMs from different human embryonic stem cell and iPSC lines. Hawthorn further prolonged field potential durations in LQTS2 CMs but reduced the beating frequencies and occurrence of immature field potentials triggered by β1-adrenergic stimulation in CPVT1 CMs at 300 and 1000 µg/ml. Furthermore, isoquercetin and vitexin flavonoids significantly slowed down isoproterenol (5 µM)-induced beating frequencies at 3 and 10 µg/ml. Therefore, C. pentagyna leaf extract and its isoquercetin and vitexin flavonoids may be introduced as a novel nutraceutical with antiarrhythmic potential for CPVT1 patients.-Pahlavan, S., Tousi, M. S., Ayyari, M., Alirezalu, A., Ansari, H., Saric, T., Baharvand, H. Effects of hawthorn ( Crataegus pentagyna) leaf extract on electrophysiologic properties of cardiomyocytes derived from human cardiac arrhythmia-specific induced pluripotent stem cells.

KEYWORDS:

CPVT1; LQTS2; in vitro drug testing; nutraceuticals

PMID:
29133340
DOI:
10.1096/fj.201700494RR
[Indexed for MEDLINE]

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