Oxidative stress is a risk factor for mammary health, resulting in decreased milk yield and milk quality. Application of exogenous bioactive compounds has been a research focus of antioxidation of animals in the mammary gland. Quercetin is a flavonoid extracted from vegetables, fruits and tea and has been shown to have a variety of biological activities, but the effect of quercetin on redox imbalance in mammary epithelial cells is unclear. In this study, cells of HC11, a mouse mammary epithelial cell line, were treated with quercetin, and the effects and molecular mechanisms of quercetin protection on hydrogen peroxide-induced oxidative stress were studied. Results showed that 20 μΜ quercetin attenuated hydrogen peroxide-induced lactate dehydrogenase release and reactive oxygen species (ROS) accumulation and alleviated the reduction of cell viability and antioxidant capacity. Quercetin significantly restored the activation of mitogen-activated protein kinase (MAPK) and nuclear factor E2-related factor 2 (Nrf2) pathways induced by hydrogen peroxide. Importantly, the inhibitors of p38 MAPK and extracellular regulated protein pathways affected the activation of Nrf2 pathway. All inhibitors of MAPK and Nrf2 pathways reduced the protective effects of quercetin on cell proliferation, the activity of catalase and the expression of glutamate-cysteine ligase modifier subunit. Meanwhile, the effects of quercetin on the production of ROS and expression of glutamate/cystine reverse transporter light chain were mainly dependent on Nrf2 pathway. In summary, the protective effect of quercetin in mammary epithelial cells was mediated via MAPK and Nrf2 pathways.

Halloysite nanotubes (HNTs) have attracted much attention as delivery carriers for various drugs, but the loading of one such drug, quercetin, on HNTs has been investigated only rarely and usually involved cyclic vacuum pumping. The main objective of the present study was to develop a novel carrier system based on HNTs for quercetin delivery without a vacuum process and to investigate the effect of chemical modification of HNTs on the loading and release of quercetin. For this purpose, comparative studies of five chemical modification reagents (sodium lauroamphoacetate, cocoamidopropyl betaine, 1-hydroxyethyl 2-nonyl imidazoline betaine, triethanolamine, and dipicolinic acid) functionalized on HNTs were investigated for quercetin loading and in vitro release. Characterization of raw halloysite, modified halloysite, and quercetin-loaded halloysite were done by X-ray diffraction (XRD), Fourier-transform infrared spectrometry (FTIR), thermogravimetric analysis (TGA), and transmission electron microscopy (TEM). The results indicated that chemical modification could improve the interactions between HNTs and quercetin. After chemical modification, quercetin was anchored to both the inner and outer surfaces of HNTs by electrostatic attraction, hydrogen bonding, and van der Waals forces. Sodium lauroamphoacetate-modified HNTs were given the highest loading of 1.96 wt.% among the five reagents. Cocamidopropyl betaine-modified HNTs exhibited the best sustained-release profile with only 29.07% for initial burst release and 480 h of consecutive release. Carboxyl groups of the modification reagent improved the loading capacity of quercetin. Amide groups prolonged drug release due to the strong affinity between amine and phenolic hydroxyl groups of quercetin. The release of quercetin from the cocamidopropyl betaine-modified HNTs fitted a first-order kinetics model well. The present study suggested that cocamidopropyl betaine-modified HNTs offer promise as vehicles for delivery of quercetin and for extending the application of quercetin.

Regarding the low number of embryos that reach the blastocyst stage when cultured in vitro, this study aimed to evaluate the effects of quercetin on pre-implantation mouse (Mus musculus) embryos obtained using in vitro fertilization, especially during the passage from morula to blastocyst. Furthermore, we studied whether quercetin also affected the expression of hypoxia-inducible factor 1α (HIF-1α). The culture medium for the embryos was supplemented with quercetin, for long or short periods of time, and then the development potential, total cell number, apoptosis rates and expression of HIF-1α were studied to determine the effect of quercetin. Embryos failed to develop when cultured for long periods of time with quercetin, implying the possible toxic effects of this, alternatively antioxidant, compound. However, a short culture from morula to blastocyst significantly improved the development potential of in vitro produced embryos, increasing the final total cell number and reducing the apoptosis rate, observing similar results to those embryos cultured in low-oxygen concentrations or developed in utero. Furthermore, in embryos treated with quercetin for 2 or 4 h we found an increase in HIF-1α compared with untreated embryos. This work could imply a way to use quercetin in fertility clinics to improve the production of healthy blastocysts and, consequently, increase the success rates in assisted reproduction techniques.

Flavonoids are natural compounds derived from fruits, vegetables and medicinal plants. These compounds have been reported to possess various biological actions including anti-inflammatory, antioxidant, growth promoter, antiviral, hepatoprotective, antibacterial, antiallergic, anticarcinogenic, antithrombotic and immunomodulator activities in various animals and poultry species. Quercetin is found in various foods such as vegetables, tea, fruits, wine apples and onions and is known to exert positive effects on poultry production and health. Since, quercetin enhances the immune system by stimulating lymphocytes, macrophages and IgY antibody production and improving natural killer cell activity, lymphoid organs (spleen, thymus and bursa) weights as well as activating the cytokines profile, its supplementation can lead to a state of immune alertness and a lower incidence of infections and diseases. In addition, it affects the dendritic cells (DCs) that play an important role in adaptive and innate immunity. Quercetin revokes the ability of lipopolysaccharide (LPS)-stimulated dendritic cells to induce specific T cell activation and reduce the cytotoxicity in both in vivo and in vitro studies, suggesting quercetin works as an immunosuppressive agent. As immune function is crucial for poultry productivity and prosperity, this review elucidates the potential nutritional effects and health benefits of quercetin on poultry as a replacer for traditional immune boosters and growth promoters. It includes the antiviral activity of quercetin against influenza A virus, rhinovirus (caused common cold), adenovirus (source of necrotic pancreatitis in broilers) and suggests its role in counteracting heavy metal toxicity. However, further studies on molecular basis are required to understand mode of action, beneficial applications as a natural feed additive, growth promoter and immune enhancer, beside the side effects of this compound in poultry.

Increased dietary intake and tissue status of the long-chain n-3 PUFA, EPA and DHA, is associated with cardiovascular benefits. Epidemiological and animal studies suggest that concomitant nutritive intake of flavonoids may increase the conversion of α-linolenic acid (ALA) to longer-chain n-3 fatty acids EPA and DHA. We investigated the effects of increased ALA intake on fatty acid composition of serum phospholipids and erythrocytes in metabolically healthy men and women and whether fatty acid profiles and ALA conversion were affected by regular quercetin intake or sex. Subjects (n 74) were randomised to receive at least 3·3 g/d ALA with either 190 mg/d quercetin (ALA+quercetin) or placebo (ALA+placebo) in a double-blinded, placebo-controlled, crossover trial with 8-week intervention periods separated by an 8-week washout period. A total of seven subjects dropped out for personal reasons. Data from the remaining sixty-seven subjects (thirty-four males and thirty-three females) were included in the analysis. Both interventions significantly increased serum phospholipid ALA (ALA+placebo: +69·3 %; ALA+quercetin: +55·8 %) and EPA (ALA+placebo: +37·3 %; ALA+quercetin: +25·5 %). ALA + quercetin slightly decreased DHA concentration by 9·3 %. Erythrocyte ALA and EPA significantly increased with both interventions, whereas DHA decreased. Fatty acid composition did not differ between sexes. We found no effect of quercetin. Intake of 3·6 g/d ALA over an 8-week period resulted in increased ALA and EPA, but not DHA, in serum phospholipids and erythrocytes. Neither quercetin supplementation nor sex affected the increment of ALA and relative proportions of n-3 PUFA in serum phospholipids and erythrocytes.

Epidemiological data on consumption of flavonoid-containing food points to the notion that some of these secondary plant metabolites may favour healthy ageing. The aim of the present paper was to review the literature on lifespan extension by flavonoids in worms, flies and mice. In most studies, worms and flies experienced lifespan extension when supplemented with flavonoids either as extracts or single compounds. Studies with mutant worms and flies give hints as to which gene products may be regulated by flavonoids and consequently enhance longevity. We discuss the data considering putative mechanisms that may underlie flavonoid action such as energy-restriction-like effects, inhibition of insulin-like-growth-factor signalling, induction of antioxidant defence mechanisms, hormesis as well as antimicrobial properties. However, it remains uncertain whether human lifespan could be prolonged by increased flavonoid intake.

Elevated plasma uric acid concentration is a risk factor for gout, insulin resistance and type 2 diabetes. Quercetin, a flavonoid found in high levels in onions, tea and apples, inhibits xanthine oxidoreductase in vitro, the final step in intracellular uric acid production, indicating that quercetin might be able to lower blood uric acid in humans. We determined the effects of 4 weeks of oral supplementation of quercetin on plasma uric acid, blood pressure and fasting glucose. This randomised, double-blinded, placebo-controlled, cross-over trial recruited twenty-two healthy males (19–60 years) with baseline plasma uric acid concentration in the higher, but still considered healthy, range (339 (sd 51) µmol/l). The intervention included one tablet containing 500 mg quercetin daily for 4 weeks, compared with placebo, with a 4-week washout period between treatments. The primary outcome was change in concentrations of plasma uric acid after 2 and 4 weeks; secondary outcome measures were changes in fasting plasma glucose, 24-h urinary excretion of uric acid and resting blood pressure. After quercetin treatment, plasma uric acid concentrations were significantly lowered by −26·5 µmol/l (95 % CI, −7·6, −45·5; P=0·008), without affecting fasting glucose, urinary excretion of uric acid or blood pressure. Daily supplementation of 500 mg quercetin, containing the bioavailable amount of quercetin as present in approximately 100 g red onions, for 4 weeks, significantly reduces elevated plasma uric acid concentrations in healthy males.

Quercetin is ubiquitous in terrestrial plants. The cotton bollworm Helicoverpa armigera as a highly polyphagous insect has caused severe crop losses. Until now, interactions between this pest and quercetin are poorly understood at the biochemical and molecular levels. In this study, we investigated the in vivo effects of quercetin on performance of cotton bollworm and on cytochrome P450 (P450) expression. Deleterious effects of quercetin on the performance of the cotton bollworm, including growth, survival, pupation and adult emergence were observed after oral administration of 3 and 10 mg g−1 quercetin to larvae since the third instar, whereas no significant toxic effect was found at 0.1 mg g−1 quercetin treatment. Piperonyl butoxide treatment enhanced the toxicity of quercetin. In vitro metabolism studies showed that quercetin was rapidly transformed by gut enzymes of fifth instar larvae of the cotton bollworm. qRT–PCR results revealed that the effect of quercetin on P450 expression was tissue- and dose-specific. Quercetin regulated P450 expression in a mild manner, and it could serve as P450 inducer (CYP337B1, CYP6B6) or repressor (CYP337B1, CYP6B7, CYP6B27, CYP9A14, CYP6AE11, and CYP4M7). These findings are important for advancing our understanding of the biochemical and molecular response of insects to plant toxins and have implications for a smart pest control.

The polyphenol quercetin may prevent CVD due to its antihypertensive and vasorelaxant properties. We investigated the effects of quercetin after regular intake on blood pressure (BP) in overweight-to-obese patients with pre-hypertension and stage I hypertension. In addition, the potential mechanisms responsible for the hypothesised effect of quercetin on BP were explored. Subjects (n 70) were randomised to receive 162 mg/d quercetin from onion skin extract powder or placebo in a double-blinded, placebo-controlled cross-over trial with 6-week treatment periods separated by a 6-week washout period. Before and after the intervention, ambulatory blood pressure (ABP) and office BP were measured; urine and blood samples were collected; and endothelial function was measured by EndoPAT technology. In the total group, quercetin did not significantly affect 24 h ABP parameters and office BP. In the subgroup of hypertensives, quercetin decreased 24 h systolic BP by −3·6 mmHg (P=0·022) when compared with placebo (mean treatment difference, −3·9 mmHg; P=0·049). In addition, quercetin significantly decreased day-time and night-time systolic BP in hypertensives, but without a significant effect in inter-group comparison. In the total group and also in the subgroup of hypertensives, vasoactive biomarkers including endothelin-1, soluble endothelial-derived adhesion molecules, asymmetric dimethylarginine, angiotensin-converting enzyme activity, endothelial function, parameters of oxidation, inflammation, lipid and glucose metabolism were not affected by quercetin. In conclusion, supplementation with 162 mg/d quercetin from onion skin extract lowers ABP in patients with hypertension, suggesting a cardioprotective effect of quercetin. The mechanisms responsible for the BP-lowering effect remain unclear.

Chronic ingestion of apple pectin has been shown to increase the absorption of quercetin in rats. The present study was designed to elucidate whether the simultaneous ingestion of quercetin with apple pectin could enhance the absorption of quercetin in humans, and the effects of dose dependency and degree of pectin methylation on quercetin absorption were also investigated. Healthy volunteers (n 19) received 200 ml of 0·5 mg/ml of quercetin drinks with or without 10 mg/ml of pectin each in a randomised cross-over design study with over 1-week intervals; urine samples from all the subjects were collected within 24 h after ingestion of the test drinks, and urinary deconjugated quercetin and its metabolites were determined using HPLC. The sum of urinary quercetin and its metabolites excreted was increased by 2·5-fold by the simultaneous ingestion of pectin. The metabolism of methylated quercetin (isorhamnetin and tamarixetin) was not affected by pectin ingestion. In six volunteers, who received quercetin drinks containing 0, 3 and 10 mg/ml of pectin, the sum of urinary quercetin and its metabolites excreted also increased in a pectin dose-dependent manner. Furthermore, the simultaneous ingestion of quercetin with low-methoxy and high-methoxy pectin, respectively, increased the sum of urinary excretion of quercetin and its metabolites by 1·69-fold and significantly by 2·13-fold compared with the ingestion of quercetin without pectin. These results elucidated that apple pectin immediately enhanced quercetin absorption in human subjects, and that its enhancing effect was dependent on the dose and degree of pectin methylation. The results also suggested that the viscosity of pectin may play a role in the enhancement of quercetin absorption.

Dietary lignans, quercetin and resveratrol have oestrogenic properties, and animal studies suggest that they synergistically decrease cancer risk. A protective effect of lignans on the development of oesophageal cancer in humans has recently been demonstrated, and the present study aimed to test whether these three phytochemicals synergistically decrease the risk of oesophageal cancer. Data from a Swedish nationwide population-based case–control study that recruited 181 cases of oesophageal adenocarcinoma (OAC), 158 cases of oesophageal squamous-cell carcinoma (OSCC), 255 cases of gastro-oesophageal junctional adenocarcinoma (JAC) and 806 controls were analysed. Exposure data were collected through face-to-face interviews and questionnaires. The intake of lignans, quercetin and resveratrol was assessed using a sixty-three-item FFQ. Reduced-rank regression was used to assess a dietary pattern, and a simplified dietary pattern score was categorised into quintiles on the basis of the distribution among the control subjects. Unconditional multivariable logistic regression provided OR with 95 % CI, adjusted for all the potential risk factors. A dietary pattern rich in lignans, quercetin and resveratrol was mainly characterised by a high intake of tea, wine, lettuce, mixed vegetables, tomatoes, and whole-grain bread and a low intake of milk. There were dose-dependent associations between simplified dietary pattern scores and all types of oesophageal cancer (all P for trend < 0·05). On comparing the highest quintiles with the lowest, the adjusted OR were found to be 0·24 (95 % CI 0·12, 0·49) for OAC, 0·31 (95 % CI 0·15, 0·65) for OSCC, and 0·49 (95 % CI 0·28, 0·84) for JAC. The results of the present study indicate that a dietary pattern characterised by the intake of lignans, quercetin and resveratrol may play a protective role in the development of oesophageal cancer in the Swedish population.

Since it is known that dietary fats improve the bioavailability of the flavonol quercetin, we purposed to investigate whether this effect is due to increased lymphatic transport of quercetin. In rats with implanted catheters in the thoracic lymph duct, we administered quercetin into the duodenum with TAG emulsions containing either long-chain fatty acids (LCT) or medium-chain fatty acids (MCT). Controls received quercetin together with a glucose solution. LCT administration increased the lymphatic output of quercetin (19·1 (sem 1·2) nmol/8 h) as well as the lymph-independent bioavailability of the flavonol, determined as area under the plasma concentration curve (1091 (sem 142) μm× min). Compared with glucose administration, MCT neither increased the lymphatic output (12·3 (sem 1·5) nmol/8 h) nor the bioavailability of quercetin (772 (sem 99) μm× min) significantly (glucose group: 9·8 (sem 1·5) nmol/8 h and 513 (sem 55) μm× min, respectively). Because LCT are released within chylomicrons into the intestinal lymph while MCT are mainly released into the portal blood, we conclude from the present results that dietary fats that are mainly composed of LCT improve quercetin bioavailability by increasing its transport via the lymph, thereby circumventing hepatic first-pass metabolism of the flavonol. In addition, LCT could enhance quercetin absorption by improving its solubility in the intestinal tract.

Phase II metabolising enzymes enable the metabolism and excretion of potentially harmful substances in adults, but to date it is unclear whether dietary phytochemicals can induce phase II enzymes differently between adults and infants. We investigated the expression of phase II enzymes in an in vitro model of primary skin fibroblasts at three different developmental stages, 1 month, 2 years and adult, to examine potential differences in age-related phase II enzymes in response to different phytochemicals (5–20 μm) including sulphoraphane, quercetin and catechin. Following phytochemical treatment, a significant increase in mRNA of glutathione S-transferase A1 (GSTA1) and NAD(P)H:quinone oxidoreductase 1 (NQO1) was observed, with the most marked increases seen in response to sulphoraphane (3–10-fold for GSTA1, P = 0·001, and 6–35-fold for NQO1, P = 0·001–0·017). Catechin also induced 3–5-fold changes in NQO1 transcription, whereas quercetin had less effect on NQO1 mRNA induction in infant cells. Moreover, NQO1 protein levels were significantly increased in 2-year-old and adult cell models in response to sulphoraphane treatment. These results suggest that metabolic plasticity and response to xenobiotics may be different in infants and adults; and therefore the inclusion of phytochemicals in the infant diet may modulate their induction of phase II metabolism, thereby providing increased protection from potentially harmful xenobiotics in later life.

The flavonol quercetin, is one of the major flavonoids found in edible plants. The bioavailability of quercetin in humans may be influenced by the food matrix in which it is consumed as well as by its chemical and physical form. The objective of the present study was to investigate the biokinetics of quercetin from quercetin-enriched cereal bars and quercetin powder-filled hard capsules. In a randomised, single-blinded, diet-controlled cross-over study, six healthy women aged 22–28 years took a single oral dose of approximately 130 mg quercetin equivalents from either quercetin-enriched cereal bars (containing 93·3 % quercetin aglycone plus 6·7 % quercetin-4′-glucoside) or quercetin powder-filled hard capsules (100 % quercetin aglycone). Blood samples were drawn before and after quercetin administration over a 24 h period. The concentrations of quercetin and its monomethylated derivatives, isorhamnetin (3′-O-methyl quercetin) and tamarixetin (4′-O-methyl quercetin), were measured by HPLC with fluorescence detection after plasma enzymatic treatment. The systemic availability as determined by comparing the plasma concentration–time curves of quercetin was found to be five times and the cmax values six times higher after ingestion of 130 mg quercetin by quercetin-enriched cereal bars than after ingestion by quercetin capsules. In contrast, tmax did not differ significantly between the two treatments. The cmax values for isorhamnetin and tamarixetin were four and nine times higher after ingestion of quercetin by quercetin-enriched cereal bars than after ingestion by quercetin capsules. In conclusion, quercetin from quercetin-enriched cereal bars is significantly more bioavailable than from quercetin powder-filled hard capsules.

Anthocyanin indexes, quercetin, kaempferol and myricetin may provide industry with potential new medicines or nutraceuticals. Velvetleaf (Abutilon theophrasti Medik) leaves from 42 plant introductions (PI) were analyzed for anthocyanin indexes while both leaves and fruit were used for quercetin, kaempferol and myricetin concentration analysis by reverse-phase high performance liquid chromatography. Leaf anthocyanin indexes ranged from 6.15 to 11.25 among PI. Leaf quercetin and kaempferol concentrations ranged from 1.50 to 4.79 mg/g and 0.43 to 2.17 mg/g, respectively. Fruit quercetin, kaempferol and myricetin concentrations ranged from 0.061 to 0.266 mg/g, 0.054 to 0.734 mg/g, and 0 to 35.87 μg/g, respectively. Significant differences in leaf weight were also observed. Significant correlations were found between several traits. This information regarding anthocyanin indexes, quercetin, kaempferol and myricetin concentrations will be useful for velvetleaf cultivar development. Breeders and other scientists could use this germplasm that contains high concentrations of anthocyanins, quercetin, kaempferol and myricetin to develop new medicines or nutraceuticals from an extremely useful weedy species.

Due to their ubiquitous distribution, flavonoids from different classes are commonly present together in foods. However, little is known about the interactions between them. The flavonol quercetin and the flavan-3-ol (+)-catechin are among the most abundant flavonoids in the diet. In the present study, we have analysed the interactions between these two flavonoids on vascular function using two pure compounds and mixtures of these flavonoids in 1:0·1, 1:1 or 1:10 proportions. Quercetin induced a more potent concentration-dependent relaxant effect than catechin in the isolated rat aorta, and the isobolographic analysis of the mixtures showed no synergistic or antagonistic effects between them, i.e. their effects were additive. Quercetin was more potent in mesenteric than in pulmonary arteries. Catechin had weak effects in these vessels and did not modify the effects of quercetin. Endothelial dysfunction induced by increased oxidative stress by the superoxide dismutase inhibitor diethyldithiocarbamate was prevented by quercetin, whereas catechin showed a weak effect and the 1:1 mixture an intermediate effect compared with the pure compounds. Quercetin but not catechin showed a pro-oxidant and NO-scavenging effect, which was not prevented by catechin. In conclusion, catechin was less potent than quercetin as a vasodilator, pro-oxidant or to prevent endothelial dysfunction, and there were no synergistic interactions between quercetin and catechin.

Quercetin, a flavonoid found in fruits and vegetables, is a strong antioxidant with anti-inflammatory, antimicrobial and immune-modulating properties. The purpose of the present study was to investigate the effects of long-term quercetin supplementation on innate immune function and inflammation in human subjects. Female subjects (n 120; aged 30–79 years) were recruited from the community and randomised to one of three groups, with supplements administered using double-blinded procedures: 500 mg quercetin/d (n 38), 1000 mg quercetin/d (n 40) or placebo (n 42). Subjects ingested two soft chew supplements twice daily during the 12-week study period. Fasting blood samples were obtained pre- and post-study and were analysed for plasma quercetin, IL-6, TNF-α and leucocyte subset cell counts. Natural killer cell activity (NKCA) and lymphocyte subsets were assessed in a subset of seventy-four subjects. Granulocyte oxidative burst activity (GOBA) and phagocytosis were assessed in sixty-four subjects. Eighteen subjects had overlapping data. Quercetin supplementation at two doses compared with placebo increased plasma quercetin (interaction effect; P < 0·001) but had no significant influence on blood leucocyte subsets, plasma IL-6 or TNF-α concentration, NKCA, GOBA or phagocytosis. NKCA was inversely correlated with BMI (r − 0·25; P = 0·035) and body fat percentage (r − 0·38; P = 0·001), and positively correlated with self-reported physical fitness level (r 0·24; P = 0·032). In summary, results from the present double-blinded, placebo-controlled, randomised trial indicated that quercetin supplementation at 500 and 1000 mg/d for 12 weeks significantly increased plasma quercetin levels but had no influence on measures of innate immune function or inflammation in community-dwelling adult females.

Quercetin has been described as having a wide range of beneficial effects in humans, ranging from anti-carcinogenic properties to reducing the risk of CVD. Nevertheless, underlying molecular mechanisms have been mostly investigated in vitro. Here, we tested whether a daily supplementation of quercetin leads to reproducible changes in human monocyte gene expression profiles. In study I, quercetin in varying dosages was given to healthy subjects for 2 weeks. RNA from monocytes isolated at the beginning and end of the study from subjects receiving 150 mg quercetin per d was subjected to transcriptome-wide microarray analysis. In study II, a double-blind cross-over study, twenty subjects exhibiting a ‘cardiovascular risk phenotype’ received 150 mg quercetin or placebo daily for 6 weeks each and served as the verification group. Microarray analysis revealed a number of differentially expressed genes. The most significantly represented functional groups were those of the immune system, nucleic acid metabolism, apoptosis and O-glycan biosynthesis. Twenty-four genes were chosen for technical replication and independent verification by quantitative real-time PCR. When comparing placebo and quercetin treatment, four genes showed significantly different expression changes (C1GALT1, O-glycan biosynthesis; GM2A, glycolipid catabolism; HDGF, cell proliferation; SERPINB9, apoptosis). However, these were minimal in respect to magnitude of fold change. In conclusion, although microarray analysis revealed extensive effects of quercetin on gene expression, the employment of a placebo-controlled study design showed no comparable results for twenty-four verification targets. This emphasises the need for stringent designs in nutritional intervention studies with the aim to identify relevant changes in gene expression.

We evaluated the effects of the two main kiwifruit cultivars (gold kiwifruit (GOK) and green kiwifruit (GRK)) and their active phenolic compound, quercetin, on H2O2-induced inhibition of gap-junction intercellular communication (GJIC) in WB-F344 rat liver epithelial cells. We found that both GOK and GRK protect WB-F344 cells from H2O2-induced inhibition of GJIC. The extracellular signal-regulated protein kinase 1/2 (ERK1/2)–connexin 43 (Cx43) signalling pathway is crucial for the regulation of GJIC, and both GOK and GRK blocked the H2O2-induced phosphorylation of Cx43 and ERK1/2 in WB-F344 cells. Quercetin alone attenuated the H2O2-mediated ERK1/2–Cx43 signalling pathway and consequently reversed H2O2-mediated inhibition of GJIC in WB-F344 cells. A free radical-scavenging assay using 1,1-diphenyl-2-picrylhydrazyl showed that the scavenging activity of quercetin was higher than that of a synthetic antioxidant, butylated hydroxytoluene, per mol, suggesting that the chemopreventive effect of quercetin on H2O2-mediated inhibition of ERK1/2–Cx43 signalling and GJIC may be mediated through its free radical-scavenging activity. Since the carcinogenicity of reactive oxygen species such as H2O2 is attributable to the inhibition of GJIC, GOK, GRK and quercetin may have chemopreventive potential by preventing the inhibition of GJIC.