Hydroxysafflor Yellow A Protects Cardiac Myocytes During Anoxia and Reoxygenation

Abstract

Coronary heart disease is a leading cause of death worldwide, causing a reduction in blood flow that leads to damage of heart tissue. Much of this damage occurs via opening of the mitochondrial permeability transition pore (MPTP). Preventing this pore's opening is therefore a useful therapeutic goal in treating cardiovascular disease. Hydroxysafflor yellow A (HSYA, a yellow principle from the safflower, Carthamus tinctorius) has been proposed as a nontoxic alternative to other agents which reduce MPTP opening. In this study, we proposed that HSYA prevents MPTP formation/opening in anoxic cardiac myocytes, and thus should protect the cells from morphologic changes seen during reoxygenation. We used isolated cardiac myocytes in an established anoxia/reoxygenation protocol to examine the cardioprotective potential of both HSYA and cyclosporine A (CsA, an agent known to inhibit MPTP formation). HSYA moderated both the reduction of viability and the loss of rods which attend anoxia and reoxygenation. The pattern of HSYA's protective effect was similar to that of CsA. The appearance of rigor forms (dependent on ATP/ADP, not calcium or MPTP opening) was unaffected by either agent. Experiments with HSYA transport indicate that roughly 50% of extracellular HSYA crosses the cell membrane in a 2-hour incubation (i.e., enough to have an effect). We conclude that HSYA can successfully enter the cardiac myocyte, and is able to moderate anoxia/reoxygenation- induced damage by interacting with the MPTP.