Planta Med 2018; 84(08): 507-518
DOI: 10.1055/s-0043-122501
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Cardioprotective Effect of Hydroxysafflor Yellow A via the Cardiac Permeability Transition Pore

Gavin A. Huber
Department of Physiology, Kirksville College of Osteopathic Medicine, A. T. Still University of Health Sciences, Kirksville, MO, USA
,
Sydney M. Priest
Department of Physiology, Kirksville College of Osteopathic Medicine, A. T. Still University of Health Sciences, Kirksville, MO, USA
,
Timothy P. Geisbuhler
Department of Physiology, Kirksville College of Osteopathic Medicine, A. T. Still University of Health Sciences, Kirksville, MO, USA
› Author Affiliations
Further Information

Publication History

received 06 June 2017
revised 26 October 2017

accepted 02 November 2017

Publication Date:
17 November 2017 (eFirst)

Abstract

Myocardial ischemia damages cardiac myocytes in part via opening of the mitochondrial permeability transition pore. Preventing this poreʼs opening is therefore a useful therapeutic goal in treating cardiovascular disease. Hydroxysafflor yellow A has been proposed as a nontoxic alternative to other agents that modulate mitochondrial permeability transition pore opening. In this study, we proposed that hydroxysafflor yellow A prevents mitochondrial permeability transition pore formation in anoxic cardiac myocytes, and thus protects the cell from damage seen during reoxygenation of the cardiac myocytes. Experiments with hydroxysafflor yellow A transport in aerobic myocytes show that roughly 50% of the extracellular dye concentration crosses the cell membrane in a 2-h incubation. In our anoxia/reoxygenation protocol, hydroxysafflor yellow A modulated both the reduction of viability and the loss of rod-shaped cells that attend anoxia and reoxygenation. Hydroxysafflor yellow Aʼs protective effect was similar to that of cyclosporin A, an agent known to inhibit mitochondrial permeability transition pore opening. In additional experiments, plated myocytes were loaded with calcein/MitoTracker Red, then examined for intracellular dye distribution/morphology after anoxia/reoxygenation. Hydroxysafflor yellow A-containing cells showed a cardioprotective pattern similar to that of cyclosporin A (an agent known to close the mitochondrial permeability transition pore). We conclude that hydroxysafflor yellow A can enter the cardiac myocyte and is able to modulate anoxia/reoxygenation-induced damage by interacting with the mitochondrial permeability transition pore.