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

机译:槲皮素及其体内代谢产物在保护H9c2细胞抗氧化应激中的作用

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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 H_2O_2-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 H_2O_2 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 H_2O_2 cardiotoxicity and that the mechanism of its action involves the modulation of PI3K/Akt and ERK1/2 signalling pathways.
机译:这项研究的目的是研究槲皮素及其两个“体内”代谢产物3'-O-甲基槲皮素和4'-O-甲基槲皮素保护H9c2心肌母细胞免受H_2O_2诱导的氧化应激的潜力。由于关于槲皮素及其代谢产物在心脏细胞中的潜在摄取和细胞作用的可用数据有限,因此我们评估了这三种化合物的细胞缔合/摄取及其在调节两种促存活信号途径中的作用:ERK1 / 2信号级联和PI3K / Akt途径。三种黄酮醇与细胞的结合程度不同。槲皮素及其两个O-甲基化代谢产物能够减少细胞内ROS的产生,但是只有槲皮素才能抵消H_2O_2细胞的损伤,这通过MTT还原测定,caspase-3活性和DNA片段化测定来测量。此外,仅观察到槲皮素通过ERK1 / 2和PI3K / Akt途径调节促生存信号。总之,我们证明了槲皮素而不是其O-甲基化的代谢物具有抗H_2O_2心脏毒性的作用,并且其作用机理涉及PI3K / Akt和ERK1 / 2信号通路的调节。

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