Direct Cardiotonic Action of Quercetin, a Plant Flavonoid, through Mechanism Independent of its Anti-Oxidative Action

Abstract

Quercetin (3, 3′, 4′, 5, 7-pentahydroxyflavone, QCT) is a major flavonoid of plants, known to exhibit anti-oxidative, anti-inflammatory, and anti-cancer effects. QCT has been demonstrated to have a cardioprotective effect through its antioxidant activity. In the present study, we found that QCT markedly enhanced the contractility of a single cardiomyocyte isolated from mouse hearts in a dynamic fashion even under conditions with no apparent oxidative stress. Simultaneous measurement of Ca2+ transient in a Fura-2 loaded single cardiomyocyte revealed that QCT markedly increased the cytoplasmic Ca2+ both at diastole and systole under regular electrical stimulation. Echocardiography revealed that intravenous administration of QCT also increased the left ventricular systolic function of the heart evaluated by ejection fraction in mice with reduced cardiac function due to a mutation causing genetic dilated cardiomyopathy (delK210 mutation in cardiac troponin T). QCT did not change the maximum force-generating capability and Ca2+ sensitivity of force generation in skinned (membrane-permeabilized) cardiac muscle fibers prepared from mouse hearts, indicating that QCT has no direct effects on the contractile machinery in cardiomyocytes. These findings indicates that QCT has a direct cardiotonic effect through enhancing the Ca2+ transient in cardiomyocytes independently of its anti-oxidative action. Studies on the molecular mechanisms underlying these phenomena are in progress.