Role of quercetin and its in vivo metabolites in protecting H9c2 cells against oxidative stress

Angeloni, C., Spencer, J.P.E. ORCID: https://orcid.org/0000-0003-2931-7274, Leoncini, E., Biagi, P.L. and Hrelia, S. (2007) Role of quercetin and its in vivo metabolites in protecting H9c2 cells against oxidative stress. Biochimie, 89 (1). pp. 73-82. ISSN 0300-9084 doi: 10.1016/j.biochi.2006.09.006

Abstract/Summary

The aim of this study was to investigate the potential of quercetin and two of its "in vivo" metabolites, 3'-O-methyl quercetin and 4'-O-methyl quercetin, to protect H9c2 cardiomyoblasts against H2O2-induced oxidative stress. As limited data are available regarding the potential uptake and cellular effects of quercetin and its metabolites in cardiac cells, we have evaluated the cellular association/uptake of the three compounds and their involvement in the modulation of two pro-survival signalling pathways: ERK1/2 signalling cascade and PI3K/Akt pathway. The three flavonols associated with cells to differing extents. Quercetin and its two O-methylated metabolites were able to reduce intracellular ROS production but only quercetin was able to counteract H2O2 cell damage, as measured by MTT reduction assay, caspase-3 activity and DNA fragmentation assays. Furthermore, only quercetin was observed to modulate pro-survival signalling through ERK1/2 and PI3K/Akt pathway. In conclusion we have demonstrated that quercetin, but not its O-methylated metabolites, exerts protective effects against H2O2 cardiotoxicity and that the mechanism of its action involves the modulation of PI3K/Akt and ERK1/2 signalling pathways. (c) 2006 Elsevier Masson SAS. All rights reserved.