Quercetin in Food: Possible Mechanisms of Its Effect on Memory

Quercetin (3,3′,4′,5,7‐pentahydroxyflavone) is found in vegetables and fruits. It is one of the major flavonoids that is part of human diets. Quercetin has several pharmacological effects in the nervous system as a neuroprotective agent. In this review, we summarize the research on quercetin and its role in memory in both animals and humans. Articles were chosen from the Scopus, PubMed, and Web of Science databases. In this review, we describe and summarize the importance of quercetin's presence in the body, particularly in the brain; its kinetics, including its absorption, metabolism, distribution, and excretion; its behavioral effects; and some of the possible mechanisms of action of quercetin on memory in different animal models. Several important pathways that may be involved in the processes of learning and memory, long‐term potentiation, and cognition may be impaired during neurological diseases or other medical conditions. As dietary quercetin is important, provision of its best formulation for delivery to the brain as a nutraceutical and in clinical translational research for the prevention or treatment of Alzheimer's disease and other types of dementia is necessary.     

The Alternate Consumption of Quercetin and Alliin in the Traditional Asian Diet Reshaped Microbiota and Altered Gene Expression of Colonic Epithelial Cells in Rats

The diet of traditional Asian is similar to the Mediterranean that was considered as a healthy dietary pattern. The report was scarce on whether different plant‐derived components with similar anti‐oxidative and anti‐inflammatory function such as quercetin and alliin in traditional Asian diet consumed in an alternate style cooperatively affect health including the growth of host and the status of the gut microbiota and colonic epithelial immunity. In the present study, the effects of alternate consumption of quercetin and alliin on host health judging by the profile of gut microbiota and gene expression of colonic epithelial cells were investigated with the Illumina MiSeq sequencing (16S rRNA genes) and Illumina HiSeq (RNA‐seq) technique, respectively. The results showed that the alternate consumption significantly increased the rat body weight and reshaped the gut microbiota composition. At the phylum level, it significantly increased the relative abundance of fecal Firmicutes and Cyanobacteria but decreased that of Bacteroidetes (P < 0.05) and increased the relative abundance of Candidatus Arthromitus, Lactococcus, Geobacillus, and Ruminococcus at the genus level that benefits the host's health. The alternate consumption of quercetin and alliin also altered 13 genes expression involved in the KEGG pathways of complement and coagulation cascades and hematopoietic cell lineage to improve the gut immunity. Therefore, the alternate consumption of quercetin and alliin in traditional Asian diet can contribute beneficial metabolic effects by optimizing gut microbiota and altering the immunologic function of colonic epithelial cells, resulting in its potential to improve the sub‐health status.     

高糖胁迫下槲皮素对酿酒酵母胞内损伤的保护作用与机制

以酿酒酵母S288c为模型,分析高糖胁迫下槲皮素对其胞内损伤的保护作用及机制。结果表明:与对照相比,高糖胁迫不影响酵母胞内活性氧(reactive oxygen species,ROS)水平,但显著降低了胞内酶比活力(P0.05);槲皮素处理后,与对照组和高糖组相比,酿酒酵母胞内ROS水平、超氧化物歧化酶和过氧化氢酶活力均显著下降(P0.05),而过氧化物酶(peroxidase,POD)比活力极显著升高(P0.01),说明POD比活力对高糖耐受性反应更为灵敏,可作为衡量高糖胁迫应激机制的重要生理指标,槲皮素可通过调节胞内POD比活力来提高机体的抗氧化能力。另外,实时荧光定量聚合酶链式反应结果表明高质量浓度葡萄糖显著抑制了酵母中GPD2和SUC2的表达水平(P0.05),并极显著提高了HXT1的表达水平(P0.01),而对GUT1的表达影响不显著;槲皮素处理后,高糖胁迫下酵母中GPD2、SUC2和HXT1的表达水平显著提高(P0.05),而GUT1无显著变化,说明槲皮素可能通过高渗透甘油途径、菊糖水解途径和己糖转运途径等来促进葡萄糖的分解代谢,从而达到保护机体细胞免受伤害的作用。结果表明槲皮素对高糖诱导的酿酒酵母胞内损伤具有保护作用,其作用机制可能与自身的抗氧化作用以及利用调节机体内高渗透甘油途径与糖的分解和转运途径存在一定的关联性。     

Bioavailability of Quercetin in Humans with a Focus on Interindividual Variation

After consumption of plant‐derived foods or beverages, dietary polyphenols such as quercetin are absorbed in the small intestine and metabolized by the body, or they are subject to catabolism by the gut microbiota followed by absorption of the resulting products by the colon. The resulting compounds are bioavailable, circulate in the blood as conjugates with glucuronide, methyl, or sulfate groups attached, and they are eventually excreted in the urine. In this review, the various conjugates from different intervention studies are summarized and discussed. In addition, the substantial variation between different individuals in the measured quercetin bioavailability parameters is assessed in detail by examining published human intervention studies where sources of quercetin have been consumed in the form of food, beverages, or supplements. It is apparent that most reported studies have examined quercetin and/or metabolites in urine and plasma from a relatively small number of volunteers. Despite this limitation, it is evident that there is less interindividual variation in metabolites which are derived from absorption in the small intestine compared to catabolites derived from the action of microbiota in the colon. There is also some evidence that a high absorber of intact quercetin conjugates could be a low absorber of microbiota‐catalyzed phenolics, and vice versa. From the studies reported so far, the reasons or causes of the interindividual differences are not clear, but, based on the known metabolic pathways, it is predicted that dietary history, genetic polymorphisms, and variations in gut microbiota metabolism would play significant roles. In conclusion, quercetin bioavailability is subject to substantial variation between individuals, and further work is required to establish if this contributes to interindividual differences in biological responses.     

Cranberry extract and quercetin modulate the expression of cyclooxygenase‐2 (COX‐2) and IκBα in human colon cancer cells

BACKGROUND: Cranberry (Vaccinium marcocarpon) fruit and quercetin, a major flavonoid found in cranberries, are likely contributors to chemoprevention, and their anti‐inflammatory activities may play a potential role in colon cancer prevention. The aim of this study was to examine the effect of cranberry extract and quercetin on basal expression of cyclooxygenase‐2 (COX‐2) and IκBα as well as the effect on phorbol 12‐myristate 13‐acetate (PMA)‐induced COX‐2 expression in colon cancer cells. RESULTS: HT‐29 human colon adenocarcinoma cells were treated with various concentrations of cranberry extract or quercetin and/or PMA, and the protein expression of COX‐2 and IκBα was determined. The results indicated that cranberry extract and quercetin decreased COX‐2 expression and suppressed degradation of IκBα in unstimulated cells. In PMA‐stimulated cells, cranberry extract was also able to decrease COX‐2 expression and suppress degradation of IκBα. CONCLUSION: The results suggest that a possible mechanism involved in the anti‐cancer activity of cranberry and quercetin is partly mediated through its anti‐inflammatory action. These findings indicate that cranberry and quercetin may reduce the risk of colon cancer possibly by suppressing inflammatory responses. Copyright © 2008 Society of Chemical Industry     

Pathway and single gene analyses of inhibited Caco-2 differentiation by ascorbate-stabilized quercetin suggest enhancement of cellular processes associated with development of colon cancer

The aim was to investigate mechanisms contributing to quercetin's previously described effects on cell-proliferation and -differentiation, which contradicted its proposed anticarcinogenic potency. In a 10-day experiment, 40 microM quercetin stabilized by 1 mM ascorbate reduced Caco-2 differentiation up to 50% (p < 0.001). Caco-2 RNA from days 5 and 10, hybridized on HG-U133A2.0 Affymetrix GeneChips(R), showed 1,743 affected genes on both days (p < 0.01). All 14 Caco-2 differentiation-associated genes showed decreased expression (p < 0.01), including intestinal alkaline phosphatase, that was confirmed technically (qRT-PCR) and functionally (enzyme-activity). The 1,743 genes contributed to 27 pathways (p < 0.05) categorized under six gene ontology (GO) processes, including apoptosis and cell-cycle. Genes within these GO-processes showed fold changes that suggest increased cell-survival and -proliferation. Furthermore, quercetin down-regulated expression of genes involved in tumor-suppression and phase II metabolism, and up-regulated oncogenes. Gene expression changes mediated by ascorbate-stabilized quercetin were concordant with those occurring in human colorectal carcinogenesis ( approximately 80-90%), but were opposite to those previously described for Caco-2 cells exposed to quercetin without ascorbate ( approximately 75-90%). In conclusion, gene expression among Caco-2 cells exposed to ascorbate-stabilized quercetin showed mechanisms contrary to what is expected for a cancer-preventive agent. Whether this unexpected in vitro effect is relevant in vivo, remains to be elucidated.     

n-3多不饱和脂肪酸对小鼠血液外泌体中miRNA的调节和抑制肥胖作用

目的：研究体内n-3多不饱和脂肪酸（n-3 polyunsaturated fatty acids,n-3 PUFAs）含量的增加对小鼠体质量和血液中外泌体miRNAs表达的影响,探讨n-3 PUFAs通过外泌体抑制肥胖的作用机制。方法：利用能自发生成n-3 PUFAs的fat-1转基因小鼠和同窝野生型小鼠（对照）,通过高脂饮食（high-fat diet,HFD）建立肥胖动物实验模型,测定小鼠体质量。提取小鼠血浆中的外泌体并鉴定;分离外泌体内的RNA,构建文库并进行miRNA高通量测序。根据测序结果通过生物信息学方法分析找到其调控的靶基因和相关联的通路,发现miRNA-靶基因互作关系。验证miRNA与肥胖的关联度以及在肥胖中所发挥的作用。结果：fat-1转基因小鼠体质量明显低于野生型;外泌体提取鉴定成功;miRNA高通量测序结果显示,不同小鼠组间进行对比时,差异表达显著（P＜0.05且差异倍数（fold change,FC）≠1）的miRNA有46 个;生物信息学分析发现6 个重要miRNA（mmu-miR-665-3p、mmu-miR-122-5p、mmu-miR-122-3p、mmu-miR-194-5p、mmu-miR-34c-5p、mmu-miR-223-3p）落在脂肪酸代谢通路以及内吞通路关键位置,功能与脂质代谢和肥胖相关,所对应的靶基因分别为Fads1、Elovl2、Elov6、Hadha、Scad1、Scad2、Hsd17b12、Acot2、Acot4和Arf6、H2-T-ps、Arrb1、Ist1、H2-T10、Wwp1、Snx4、IL2rb、Mvb12b、Rab11、fip3、Kif5a、Nedd4l。结论：n-3 PUFAs含量的增加能够有效降低小鼠的体质量,抑制肥胖。n-3 PUFAs能够调节血液中外泌体内miRNA的表达,其中具有显著差异性的miRNA与肥胖有关,其相关的靶基因集中在脂质代谢相关的分子通路中,提示可能是n-3 PUFAs降低体质量抑制肥胖机制之一。     

槲皮素抑制黄曲霉毒素产生的机制初探

研究发现茶叶中的茶多酚单体普遍具有抑制黄曲霉毒素B1(AFB1)产生的活性,而槲皮素的抑毒活性要高于等浓度下儿茶素类茶多酚。为了解槲皮素抑制黄曲霉毒素产生的分子机制,对黄曲霉菌的抗氧化系统、毒素产生的相关基因进行了分析。试验结果显示槲皮素处理能后降低黄曲霉菌内的ROS水平,降低MDA含量。RT-PCR结果证实槲皮素能够激活抗氧化系统转录因子Yap1,导致黄曲霉体内的抗氧化酶系统活性的增加,POD、CAT、SOD都得到了显著的提高,这很可能是槲皮素抑制AFB1产生的关键因素;槲皮素能同时下调AflR与AflS的表达,而AflS能够通过结合AflR调控产毒基因的表达,这很可能是槲皮素抑制AFB1产生的核心分子机制,这种机制也与其激活抗氧化系统缓解菌体内氧化胁迫的作用相对应。以上结果表明槲皮素作为一种高效的黄曲霉毒素合成抑制剂,将对提高食品安全保障具有较高的应用价值。     

Biochanin A: A phytoestrogen with therapeutic potential

BackgroundBiochanin A, a bioactive constituent obtained from Trifolium pratense (red clover) and many other legumes, has drawn considerable attention of researchers in recent years owing to its wide spectrum of pharmacological activities. It exhibits multifaceted biological activities viz. neuroprotective, anticancer, anti-oxidant, anti-inflammatory, osteogenic, anti-hyperglycemic and protective effect on endothelial cell integrity and function. The therapeutic potential of this isoflavone has been explored in various in vitro, in vivo and ex vivo models. However, in vivo evidences are limited due to its low bioavailability.Scope and approachThis review highlights the therapeutic potential of biochanin A along with the methods of its extraction, isolation and identification, and supplemented further with approaches to enhance its bioavailability. The various molecular targets through which it displays different biological roles have also been spotlighted.Key findings and conclusionBiochanin A, a potent molecule exhibits its molecular actions by targeting different phases of cell cycle; various signal transduction pathways involved in cell proliferation, cell differentiation, apoptosis, nuclear factor kappa B (NF-κB), and peroxisome proliferator-activated receptor gamma (PPAR γ). In cancer cells, biochanin A suppresses the activation of Akt and mitogen activated protein kinases (MAPKs) and also increases the expression of estrogen receptors (ERs) in other cellular models. Despite its huge potential, the clinical use of this isoflavone is limited due to its low bioavailability. Various strategies developed to enhance the bioavailability of biochanin A have led to foresee the potential of this promising molecule to increase the health benefits in future.     

Dietary Flavonoid Quercetin and Associated Health Benefits—An Overview

Phytochemicals have received a considerable attention in the present day world. Epidemiological studies have established that phytochemicals contribute more qualitatively to the total antioxidant activity of foods than nutrient antioxidants like vitamin C and vitamin E. Among polyphenols, quercetin constitutes the main flavonoid in our daily diet being particularly abundant in onions and apples. Since the realization that many folk medicines in use contain flavonoids, interest in this class of compounds has intensified. Quercetin acts as a strong reducing agent, which together with other dietary reductants such as vitamin C, vitamin E, and carotenoids protect body tissue against oxidative stress. Recent reports suggest that quercetin as antioxidant improves normal cell survival and as pro-oxidant induces apoptosis in cancerous cells whereby prevents tumor proliferation. Among other important properties like modulation of genes related to cell cycle, signal transduction, and xenobiotic metabolism, quercetin has also been attributed with antiviral, anti-inflammatory, antibacterial, and muscle-relaxing properties. In the literature, only a few in vivo studies have been carried out; therefore, before making any authentic health claim about this compound, it is essential to know its nature and its dietary origin. Furthermore, it is important to know the amount present in different diets and its bioavailability, followed by clinical trials and investigations, if researchers are to use it as an chemo-preventive and chemotherapeutic agent against various deleterious degenerative diseases.     

洋葱皮萃取物中黄酮类化合物的分析研究

本文对洋葱皮萃取物中黄酮类化合物的成分及含量进行了分析研究．从显色反应、紫外光谱、薄层色谱的分析结果表明，洋葱皮萃取物中黄酮类化合物的主要成分为游离的槲皮素及其衍生物。HPLC定量分析结果为萃取物中含游离槲皮素31．2％，总黄酮44．6％。     

Comparison of Quercetin Pharmacokinetics Following Oral Supplementation in Humans

Abstract: The objective of the study was to investigate the absorption of quercetin aglycone in 18 healthy human subjects administered via the following oral carrier systems: suspension of quercetin (quercetin QU995 powder in Tang^® and spring water), nutritional bars (First Strike?), and chews (RealFX? Q‐Plus?). Subjects were divided into 3 groups of 6 individuals each receiving 500 mg quercetin in one of the aforementioned formulations. Blood levels were monitored immediately pre‐ and for 32 h postadministration. The concentration of total quercetin in blood samples was determined by solid phase extraction followed by high‐performance liquid chromatography analysis. Pharmacokinetic parameters were determined by noncompartmental modeling using Kinetica software. The C_max of quercetin was highest with RealFX? Q‐Plus? Chews (1051.9 ± 393.1 μg/L) achieved within 3.3 h as compared to that for First Strike? Bars (698.1 ± 189.5 μg/L in 2.3 h) and Tang^® suspension (354.4 ± 87.6 μg/L in 4.7 h). The results showed no statistically significant difference in quercetin absorption among groups due to high variability within groups receiving quercetin from same dosage form. This study represents the first comprehensive evaluation of quercetin absorption from quercetin fortified oral food products at doses commonly used for quercetin supplementation. Practical Application: The current study describes for the first time, comprehensive evaluation of quercetin PK in humans from quercetin fortified oral food products at doses commonly used for quercetin supplementation. Owing to quercetin's potent antioxidant and anti‐inflammatory actions, quercetin is widely being used as a nutritional supplement. In order to maximize the bioavailability of quercetin for its use in efficacy studies, it is important to determine its ideal oral carrier system and route for its delivery. The current research unveils vital information about quercetin supplementation to the international community, especially to soldiers, athletes, and the dietary supplement industry.     

Biochemistry,cell biology and molecular biology of lipids of Saccharomyces cerevisiae

The yeast Saccharomyces cerevisiae is a powerful experimental system to study biochemical, cell biological and molecular biological aspects of lipid synthesis. Most but not all genes encoding enzymes involved in fatty acid, phospholipid, sterol or sphingolipid biosynthesis of this unicellular eukaryote have been cloned, and many gene products have been functionally characterized. Less information is available about genes and gene products governing the transport of lipids between organelles and within membranes, turnover and degradation of complex lipids, regulation of lipid biosynthesis, and linkage of lipid metabolism to other cellular processes. Here we summarize current knowledge about lipid biosynthetic pathways in S. cerevisiae and describe the characteristic features of the gene products involved. We focus on recent discoveries in these fields and address questions on the regulation of lipid synthesis, subcellular localization of lipid biosynthetic steps, cross-talk between organelles during lipid synthesis and subcellular distribution of lipids. Finally, we discuss distinct functions of certain key lipids and their possible roles in cellular processes. © 1998 John Wiley & Sons, Ltd.     

Food content, processing, absorption and metabolism of onion flavonoids

The question as to how far the development of chronic diseases in humans depends on diet still remains open. Simultaneously, epidemiological studies suggest the consumption of a flavonoids rich diet might decrease the risk of degenerative changes and certain diseases. The intake of this group of compounds as to quality and quantity depends on dietary habits and a widespread presence of quercetin in the diet makes this compound one of the key factors. Onion, one of the richest and most common quercetin sources, was particularly often studied in different aspects. Quercetin is present in onion mainly as glycosides, of which the distribution within the onion bulb changes in onion processing, and biological activities attracted a lot of attention. Especially antioxidative activity demonstrated in vitro was initially associated with most of the beneficial effects of quercetin on the human body. However, after ingestion quercetin undergoes extensive metabolism and microbial action resulting in its altered or degraded structure; therefore, most of the effects shown in in vitro experiments with the pure compound cannot be directly extrapolated to in vivo systems. Yet, this does not mean that quercetin simultaneously loses its positive impact on consumer health. Even after being metabolized it may still affect the redox balance by inducing antioxidative and detoxifying enzymes or compounds which may be involved in sustaining homeostasis.