Department of Food Technology, Safety and Health, Faculty of Bioscience Engineering, Ghent University, Ghent 9000, Belgium; Department of Plants and Crops, Faculty of Bioscience Engineering, Ghent University, Ghent 9000, Belgium.
Department of Plants and Crops, Faculty of Bioscience Engineering, Ghent University, Ghent 9000, Belgium.
Food Res Int. 2021 Jul;145:110430. doi: 10.1016/j.foodres.2021.110430. Epub 2021 May 20.
Flavonoid bioavailability and bioactivity is associated with interindividual variability, which is partially due to differences in health status. Previously, it was demonstrated that cellular stress, especially mitochondrial stress, increases intracellular quercetin uptake and this is associated with beneficial health effects. Here, the impact of quercetin on mitochondrial dysfunction, induced by stressors targeting different sites of the electron transport chain, is investigated. The influence of the mitochondrial stress on quercetin uptake and subcellular location is studied and the accumulated quercetin metabolites in intestinal Caco-2 cells and mitochondria are characterized.
It was observed that quercetin counteracted (i) the carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP)-induced decrease in maximum oxygen consumption, (ii) the valinomycin-, oligomycin- and FCCP-induced reactive oxygen species production and (iii) the valinomycin-induced disruption of mitochondrial membrane potential. Using confocal microscopy, it was found that upon mitochondrial stress, the intracellular quercetin accumulation increased and was partially located in the mitochondria. Finally, it was demonstrated that quercetin was present as O-methyl, O-methylglucuronide and O-methylsulfate conjugates in the cell lysate and mitochondria-enriched fraction.
This study shows that quercetin can partially restore, especially FCCP-induced, mitochondrial dysfunction and this protective effect was linked with an intracellular quercetin accumulation in the mitochondria of intestinal cells.
类黄酮的生物利用度和生物活性与个体间的差异有关，部分原因是健康状况的不同。此前已经证明，细胞应激，特别是线粒体应激，会增加细胞内槲皮素的摄取，这与有益的健康效应有关。在这里，研究了应激源靶向电子传递链不同部位引起的线粒体功能障碍对槲皮素的影响。研究了线粒体应激对槲皮素摄取和亚细胞定位的影响，并对肠道 Caco-2 细胞和线粒体中积累的槲皮素代谢物进行了表征。
观察到槲皮素可以（i）抵消羰基氰化物 4-（三氟甲氧基）苯腙（FCCP）诱导的最大耗氧量下降，（ii）缬氨霉素、寡霉素和 FCCP 诱导的活性氧产生，以及（iii）缬氨霉素诱导的线粒体膜电位破坏。通过共聚焦显微镜发现，在线粒体应激下，细胞内槲皮素积累增加，部分位于线粒体中。最后，证明了细胞裂解物和富含线粒体的级分中存在槲皮素的 O-甲基、O-甲基葡萄糖醛酸和 O-甲基硫酸酯缀合物。
本研究表明，槲皮素可以部分恢复，特别是 FCCP 诱导的线粒体功能障碍，这种保护作用与肠道细胞线粒体中细胞内槲皮素的积累有关。
