Cardiotonic actions of quercetin and its metabolite tamarixetin through a digitalis-like enhancement of Ca2+ transients

Abstract

The plant-derived flavonoid, quercetin (QCT), has many biological actions, including cardioprotective actions, resulting from its antioxidant and anti-inflammatory effects. In this study, effects of QCT and its metabolites on the contraction and Ca transients (CaT) of mouse single cardiomyocytes were simultaneously measured and compared with those of isoproterenol and digoxin. Furthermore, cardiac function and plasma concentrations were analyzed after bolus intravenous administration of QCT in mice. QCT and its metabolite, tamarixetin, as well as isoproterenol and digoxin, enhanced the contraction and CaT of cardiomyocytes. The inotropic action of isoproterenol was accompanied by an increase in the velocities of sarcomere shortening and relengthening and CaT decay through activation of cAMP-dependent protein kinase; however, no such lusitropic effects accompanied the inotropic action of QCT, tamarixetin or digoxin. Intravenous administration of QCT to mice resulted in a sustained increase in cardiac systolic function; QCT was rapidly metabolized to tamarixetin and its plasma concentration was maintained at high levels over a similar time frame as the enhancement of cardiac systolic function. These results suggest that QCT exerts a cardiotonic action in vivo at least, in part, through digitalis-like enhancement of CaT by itself and its metabolite tamarixetin.

Scabiosa Genus: A Rich Source of Bioactive Metabolites

“…Tamarixetin, the aglycone of compound 17 , may be the less known one and consequently less studied. Nevertheless, its in vitro ability to inhibit the proliferation of leukemia cells [56] and enhancement of the Ca 2+ transients, both in vitro and in vivo [57], have been demonstrated. Moreover, the 3- O -β- d -glucopyranoside derivative reveals ability to, in vivo, inhibit the matrix metalloproteinase-9, that can be regarded as potential drug to treat gastric ulceration [58].…”

Differential effects of the formin inhibitor SMIFH2 on contractility and Ca2+ handling in frog and mouse cardiomyocytes

“…Cardiomyocytes were isolated from the left ventricles of the wild‐type mouse hearts and from the ventricles of the bullfrog hearts as previously described (Du et al., 2007) (Hayamizu et al., 2018) with minor modifications. Briefly, the heart was perfused at 37℃ in Langendorff mode with oxygenated Krebs–Henseleit solution (118 mM NaCl, 1.0 mM KCl, 1.2 mM MgSO 4 , 1.2 mM KH 2 PO 4 , 25 mM NaHCO 3 , 0.5 mM EDTA, 5.5 mM glucose, 10 mM HEPES, pH 7.4) containing 50 mM BDM and 50 μM CaCl 2 for 10 min, and treated with oxygenated Krebs–Henseleit solution (without EDTA) containing 50 mM BDM, 50 μM CaCl 2, and collagenase type 2 (Worthington Biochemical Corp., USA) at the concentration of 65 U/ml for 30 min in the case of mouse and 500 U/ml for 60 min in the case of bullfrog's hearts.…”

Quercetin: A Bioactive Compound Imparting Cardiovascular and Neuroprotective Benefits: Scope for Exploring Fresh Produce, Their Wastes, and By-Products

“…The systolic cardiac function was enhanced in mice administrated with quercetin. The rapid metabolization of quercetin to tamarixetin was maintained at a higher concentration for enhancement of systolic cardiac function, as reported by Hayamizu et al [32]. Quercetin can exert cardiotonic action via digitalis-like enhancement of Ca 2+ transients by itself and its metabolite, tamarixetin.…”