At the crossroads from bench to bedside: luteolin is a promising pharmacological agent against myocardial ischemia reperfusion injury

Abstract

The study by Bian et al. (1) found that luteolin (Lut) inhibited myocardial ischemia/reperfusion injury (IRI) by decreasing miR-208b-3p and increasing Ets1 expression levels in rats. Cokkinos (2) has written an editorial commentary for this study and considered it to be elegant. However, he also raised several interesting questions about the study. As the members of the investigate team, we would like to discuss these issues with counterparts.The first question is how relevant to the clinical situation are results on IRI alleviation in the experimental setting. In the commentary, Cokkinos (2) cited the position paper of the Working Group of Cellular Biology of the Heart of the European Society of Cardiology (3) which published in Cardiovasc Res, 2013. According to the position paper, the experts concluded that there was no effective proven therapy against IRI. It is widely recognized that it is not always possible to translate animal experiments into clinical therapy.First of all, we reviewed the relative literatures about cardioprotection including the position paper. As now wellknown, coronary heart disease (CHD) is the leading cause of death worldwide. The main therapeutic strategy in CHD is reperfusion that could be succeeded either medicine or operation (4,5). However, its major pathophysiological manifestation is myocardial IRI. Despite all of optimal therapies, the morbidity and mortality of CHD remain significant. As such, to find more effective cardioprotective strategies has never been so pressing, novel therapeutic strategies are required to protect the heart from the detrimental effects of IRI, in order to reduce myocardial injury, preserve cardiac function and improve clinical outcomes in patients with CHD (6,7).Over the last few decades, understanding of the pathophysiology of IRI and concepts of cardioprotection has been revolutionised. Newer strategies such as ischemic preconditioning (IPC), ischemic postconditioning, and remote IPC have been shown to condition the myocardium to IRI and thus reduce the final myocardial infarct size (7). The elucidation of underlying mechanisms in different forms of ischemic conditioning has identified novel targets for cardioprotection amenable to pharmacological manipulation, so called pharmacological conditioning (8).The study for a pharmacological strategy to protect the heart against IRI preceded the discovery of IPC by many years. Over the past 3 decades, a number of pharmacological cardioprotection strategies were discovered in experimental studies (9). Researches involved conditioning mechanisms have revealed multiple receptors, pathways and end effectors, all of which can be pharmacologically stimulated, such as agents acting on cardiomyocyte receptors (adenosine, bradykinin, opioids, glucagon-like peptide 1, atrial natriuretic peptide, erythropoeitin, insulin), agents acting on intracellular signal transduction pathways (phosphodiesterase-5 inhibitors, glyceryl trinitrate or

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“…Luteolin is a widely distributed flavonoid compound that can be found in a variety of plants. A large number of studies have found that luteolin is a potential cardioprotective agent, and it also has many evidences of cardioprotection in epidemiology [24]. β-sitosterol can also be found in a variety of plants.…”