共查询到5条相似文献,搜索用时 0 毫秒
1.
2.
van der Woude H Boersma MG Alink GM Vervoort J Rietjens IM 《Chemico-biological interactions》2006,160(3):193-203
This study investigates the pro-oxidant activity of 3′- and 4′-O-methylquercetin, two relevant phase II metabolites of quercetin without a functional catechol moiety, which is generally thought to be important for the pro-oxidant activity of quercetin. Oxidation of 3′- and 4′-O-methylquercetin with horseradish peroxidase in the presence of glutathione yielded two major metabolites for each compound, identified as the 6- and 8-glutathionyl conjugates of 3′- and 4′-O-methylquercetin. Thus, catechol-O-methylation of quercetin does not eliminate its pro-oxidant chemistry. Furthermore, the formation of these A-ring glutathione conjugates of 3′- and 4′-O-methylquercetin indicates that quercetin o-quinone may not be an intermediate in the formation of covalent quercetin adducts with glutathione, protein and/or DNA. In additional studies, it was demonstrated that covalent DNA adduct formation by a mixture of [4-14C]-3′- and 4′-O-methylquercetin in HepG2 cells amounted to only 42% of the level of covalent adducts formed by a similar amount of [4-14C]-quercetin. Altogether, these results reveal the effect of methylation of the catechol moiety of quercetin on its pro-oxidant behavior. Methylation of quercetin does not eliminate but considerably attenuates the cellular implications of the pro-oxidant activity of quercetin, which might add to the mechanisms underlying the apparent lack of in vivo carcinogenicity of this genotoxic compound. The paper also presents a new mechanism for the pro-oxidant chemistry of quercetin, eliminating the requirement for formation of an o-quinone, and explaining why methylation of the catechol moiety does not fully abolish formation of reactive DNA binding metabolites. 相似文献
3.
Antioxidative flavonoid quercetin: implication of its intestinal absorption and metabolism 总被引:9,自引:0,他引:9
Quercetin is a typical flavonoid ubiquitously present in fruits and vegetables, and its antioxidant effect is implied to be helpful for human health. The bioavailability of quercetin glycosides should be clarified, because dietary quercetin is mostly present as its glycoside form. Although quercetin glycosides are subject to deglycosidation by enterobacteria for the absorption at large intestine, small intestine acts as an effective absorption site for glucose-bound glycosides (quercertin glucosides). This is because small intestinal cells possess a glucoside-hydrolyzing activity and their glucose transport system is capable of participating in the glucoside absorption. A study using a cultured cell model for intestinal absorption explains that the hydrolysis of the glucosides accelerates their absorption in the small intestine. Small intestine is also recognized as the site for metabolic conversion of quercetin and other flavonoids as it possesses enzymatic activity of glucuronidation and sulfation. Modulation of the intestinal absorption and metabolism may be beneficial for regulating the biological effects of dietary quercetin. 相似文献
4.
Quercetin (QT) was formulated into a novel self-emulsifying drug delivery system (SEDDS) to improve its oral bioavailability and antioxidant potential compared to free drug. Capmul MCM was selected as the oily phase on the basis of optimum solubility of QT in oil. Tween 20 and ethanol were selected as surfactant and cosurfactant from a large pool of excipients, depending upon their spontaneous self-emulsifying ability with the selected oily phase. Pseudoternary-phase diagrams were constructed to identify the efficient self-emulsification regions in various dilution media, viz., water, pH 1.2, and pH 6.8. The ratio of 40:40:20 w/w, Capmul MCM:QT (19:1)/Tween 20/ethanol was optimized based on its ability to form a spontaneous submicrometer emulsion in simulated gastrointestinal fluids. DPPH scavenging assay showed comparable antioxidant activity of QT-SEDDS to free QT. QT-SEDDS was robust in terms of stability against short-term excursion of freeze/thaw cycles and accelerated stability for 6 months as per International Conference on Harmonisation guidelines. A fluorescent dye-loaded SEDDS formulation showed rapid internalization within 1 h of incubation with Caco-2 cells as evident by confocal laser scanning microscopy. QT-SEDDS showed a significant increase in cellular uptake by 23.75-fold in comparison with free QT cultured with Caco-2 cells. The SEDDS demonstrated ~5-fold enhancement in oral bioavailability compared to free QT suspension. The in vitro–in vivo relation between in vitro Caco-2 cell uptake and in vivo pharmacokinetics of QT-SEDDS showed a correlation coefficient of ~0.9961, as evident from a Levy plot. Finally, QT-SEDDS showed a significantly higher in vivo antioxidant potential compared to free QT when evaluated as a function of ability to combat doxorubicin- and cyclosporin A-induced cardiotoxicity and nephrotoxicity, respectively. 相似文献
5.
Adama Gansane Issa Nebie Ouedraogo Noelie Bere Henry Issiaka Soulama Esperance Ouedraogo Jean-Baptiste Yaro Amidou Diarra Sombie Benjamin Amadou Tidiani Konate Alfred Tiono Sodiomon Bienvenu Sirima 《Memórias do Instituto Oswaldo Cruz》2013,108(5):644-650
During the season of high malaria transmission, most children are
infected by Plasmodium, which targets red blood cells (RBCs),
affecting haematological parameters. To describe these variations, we examined
the haematological profiles of two groups of children living in a
malaria-endemic area. A cross-sectional survey was conducted at the peak of the
malaria transmission season in a rural area of Burkina Faso. After informed
consent and clinical examination, blood samples were obtained from the
participants for malaria diagnosis and a full blood count. Of the 414 children
included in the analysis, 192 were not infected with
Plasmodium, whereas 222 were asymptomatic carriers of
Plasmodium infection. The mean age of the infected children
was 41.8 months (range of 26.4-57.2) compared to 38.8 months (range of
22.4-55.2) for the control group (p = 0.06). The asymptomatic infected children
tended to have a significantly lower mean haemoglobin level (10.8 g/dL vs. 10.4
g/dL; p < 0.001), mean lymphocyte count (4592/µL vs. 5141/µL; p = 0.004),
mean platelet count (266 x 103/µL vs. 385 x 103/µL; p < 0.001) and mean RBC
count (4.388 x 106/µL vs. 4.158 x 106/µL; p < 0.001) and a higher mean
monocyte count (1403/µL vs. 1192/µL; p < 0.001) compared to the control
group. Special attention should be applied when interpreting haematological
parameters and evaluating immune responses in asymptomatic infected children
living in malaria-endemic areas and enrolled in vaccine trials. 相似文献