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PubMed2006

Antioxidative effects of quercetin-glycosides isolated from the flower buds of Tussilago farfara L.

A bioassay-guided fractionation of the ethylacetate soluble fraction from the flower buds of Tussilago farfara L. (Compositae) yielded two flavonoids, quercetin 3-O-beta-L-arabinopyranoside and quercetin 3-O-beta-D-glucopyranoside. These two sugar conjugates of quercetin exhibited higher antioxidative activity than their aglycone, quercetin by NBT superoxide scavenging assay. Moreover, treatment with quercetin 3-O-beta-L-arabinopyranoside significantly increased the total glutathione (GSH) contents and the protein level of gamma-glutamylcysteine ligase (gamma-GCL), a key enzyme required for glutathione (GSH) synthesis in a rat hepatocyte cell line. Subcellular fractionation and reporter gene analysis using antioxidant response element (ARE) construct revealed that quercetin 3-O-beta-L-arabinopyranoside increased the level of nuclear Nrf2 and reporter activity, and that these were associated with the induction of the gamma-GCL gene. After 24 h incubation of cells with quercetin 3-O-beta-L-arabinopyranoside, 23% of the glycoside was converted to its aglycone, quercetin, but gamma-GCL was not induced by 7 microM (23%) quercetin. These results suggest that the two quercetin-glycosides isolated from T. farfara L. have direct antioxidative properties, and that quercetin 3-O-beta-L-arabinopyranoside increases the cellular GSH level by inducing the gamma-GCL gene. These novel effects of quercetin-glycosides are suggestive to underlie the potential putative chemopreventive effects of T. farfara L.

Animals↗
PubMed1996

Effect of quercetin on the genotoxic potential of cisplatin.

The natural product flavonoid quercetin has been shown to sensitise cells to the cytotoxic potential of cisplatin. Both cisplatin and quercetin are genotoxicants. As quercetin is currently in clinical trial as a cytotoxicant-sensitising agent, we wanted to elucidate whether it affects the genotoxicity associated with cisplatin. The genotoxic potential of both agents alone and in combination was studied in Salmonella typhimurium strains TA 98, TA 100 and TA 102 and by assessment of unscheduled DNA synthesis (UDS) in rat hepatocytes. Furthermore, effects of quercetin on levels of cisplatin-DNA adducts were studied in hepatocytes by ELISA. Cisplatin was mutagenic in all 3 bacterial strains and quercetin in strain TA 98. The number of revertant Salmonella colonies observed with the combination did not differ significantly from that caused by the drugs on their own. In the UDS assay, cisplatin was genotoxic but quercetin was not. In combination, quercetin decreased the nuclear grain count caused by cisplatin, but quercetin did not alter the level of cisplatin-DNA adduct formation in hepatocytes. Our results suggest that the mutagenic potential of the combination cisplatin-quercetin, as judged by the bacterial short-term test, does not exceed that associated with the individual components. However, in hepatocytes, quercetin appears to inhibit repair of cisplatin-induced DNA damage. Therefore, in patients who are to be treated with a combination of cisplatin and quercetin, the risk of genotoxicity in normal tissues will have to be taken into consideration.

Animals↗
PubMed2005

Physicochemical and structural characterization of quercetin-beta-cyclodextrin complexes.

Quercetin is a bioactive flavonoid widely used as a health supplement. Being sparingly soluble and chemically unstable in aqueous intestinal fluids, quercetin is poorly absorbed orally. This study aimed to investigate the effects of three beta-cyclodextrins, namely, unsubstituted beta-cyclodextrin (beta-CD), hydroxypropyl-beta-cyclodextrin (HP-beta-CD), and sulfobutyl ether beta-cyclodextrin (SBE-beta-CD) on the chemical stability and water solubility of quercetin, and to elucidate the complexation mechanisms of these beta-CDs with quercetin. Quercetin-beta-CD complexes in solution were characterized by stability assessment, phase solubility measurements, and 1H-nuclear magnetic resonance (NMR) spectroscopy. Molecular modeling was used to help establish the mode of interaction of the beta-CDs with quercetin. Solubility enhancements of quercetin obtained with the three beta-CDs followed the rank order: SBE-beta-CD > HP-beta-CD > beta-CD. The stability of quercetin at alkaline pHs also showed substantial improvement. NMR spectroscopic analysis suggested that the B-ring, C-ring, and part of the A-ring of quercetin display favorable interaction with the hydrophobic cavity of the beta-CDs, which was confirmed by molecular dynamics (MD) simulations using a solvated model of the quercetin-beta-CD complex. An inclusion complex model has been established for explaining the observed augmentation of solubility and stability of quercetin in water by beta-CDs.

Chemical Phenomena↗
PubMed2003

Effects of quercetin and rutin on vascular preparations: a comparison between mechanical and electrophysiological phenomena.

BACKGROUND: Several studies have indicated that quercetin promotes relaxation of vascular smooth muscle both in vivo and in vitro. However, Saponara et al. [(2002) Br J Pharmacol 135: 1819-1827] have demonstrated that quercetin is an activator of vascular L-type Ca(2+) channels. AIM OF THE STUDY: We investigated the mechanical and electrophysiological properties of quercetin and its rutoside, rutin, in an attempt to clarify how Ca(2+) channel activation might be related to the myorelaxing activity. METHODS: Aorta ring preparations and single tail artery myocytes were employed for functional and patch-clamp experiments, respectively. RESULTS: Rutin was found to relax intact rat aorta rings, which had been precontracted with phenylephrine (pIC(50) = 5.65 +/- 0.31) but in contrast had no effect on depolarised (60 mM K(+)) preparations or on those from which the endothelium had been removed. Furthermore, rutin did not affect L-type Ca(2+) current recorded in rat tail artery myocytes. The quercetin-induced relaxation of intact rings precontracted with phenylephrine exhibited two components characterised by 6.23 +/- 0.38 and 4.66 +/- 0.09 pIC(50), respectively. Removal of the endothelium abolished the first component, leaving the second unaltered. Moreover, quercetin was found to relax 60 mM K(+) depolarised rings with a pIC(50) of 4.59 +/- 0.03. The application of quercetin in isolated smooth muscle cells brought about a marked increase of L-type Ca(2+) current (pEC(50) = 5.09 +/- 0.05). Unlike quercetin, Bay K 8644 contracted aorta rings preincubated with 10, 20 or 30 mM K(+). The myotonic effect of Bay K 8644 was observed both in the absence or presence of 30 microM quercetin. The application of Bay K 8644 (10-100 nM) caused a further significant increase in L-type Ca(2+) current in rat tail artery myocytes stimulated with 30 microM quercetin. CONCLUSIONS: Quercetin is a naturally occurring L-type Ca(2+) channel agonist. This effect, however, is overwhelmed by quercetin-induced vasorelaxation taking place via pathways which are more relevant than L-type Ca(2+) influx in the hierarchy of functional competencies.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1985

Inhibition of cytochrome P-450 activity in rat liver microsomes by the naturally occurring flavonoid, quercetin.

The kinetic characteristics and mechanism of flavonoid inhibition of cytochrome P-450-mediated reactions were examined in rat liver microsomes, using the naturally occurring flavonoid, quercetin (3,3',4',5,7-pentahydroxyflavone). Quercetin inhibited the O-deethylation of ethoxyresorufin in beta-naphthoflavone-induced microsomes by 15-80% at concentrations of 10-250 nM. The pattern of inhibition was dependent on quercetin concentration. Quercetin also inhibited p-nitroanisole demethylation and benzo(a)-pyrene hydroxylation, but did not change the proportions of the individual benzo(a)pyrene metabolites in comparison to controls. Specific steps in the P-450 reaction pathway were tested for sensitivity to quercetin inhibition. The Km values of the P-450 substrates tested were increased in the presence of quercetin; competition for and/or alteration of the substrate binding site contributes to the mechanism of inhibition. In experiments under anaerobic, carbon monoxide-saturated conditions, quercetin did not inhibit cytochrome P-450 reduction by NADPH-cytochrome P-450 reductase. The cumene hydroperoxide-supported O-deethylation of ethoxyresorufin was inhibited by quercetin (15-60% inhibition at concentrations of 50-300 nM), suggesting that quercetin may interfere with the formation or breakdown of the oxygenated heme complex. Stoichiometry experiments established that quercetin is a potent uncoupler of P-450 reactions, elevating the rates of H2O2 formation almost twofold. Structure/activity studies indicated that certain other naturally occurring flavonoids were at least as potent inhibitors of ethoxyresorufin deethylation as quercetin. These findings are of interest in light of the significant dietary exposure of the human population to the flavonoids.

Animals↗
PubMedDate not supplied

Factors affecting the mutagenic activity of quercetin for Salmonella typhimurium TA98: metal ions, antioxidants and pH.

The mutagenic activity of quercetin for Salmonella typhimurium TA98 was inhibited by addition of metal salts. MnCl2 was a potent inhibitor, followed by CuCl2, FeSO4, and FeCl3, the probable mechanism being facilitated catalytic oxidation of quercetin. With quercetin incorporated at a level of 100 nmoles/plate, approximate doses (nmoles/plate) to give 50% inhibition of mutagenic activity were: MnCl2 less than 10 (-S9), 18 (+S9); CuCl2 65 (-S9), greater than 100 (+S9); FeSO4 190 (-S9), greater than 300 (+S9); or FeCl3 275 (-S9), greater than 300 (+S9). Ascorbate, superoxide dismutase, and, to a lesser extent, NADH and NADPH, all enhanced the mutagenic activity of quercetin in the absence of the mammalian-microsome (S9) system, but had no significant effect in the presence of the S9 mix. The maximum enhancement of activity by ascorbate or superoxide dismutase was approximately 87% of the increase achieved by addition of the S9 mix. Tyrosinase (catechol oxidase) substantially reduced the mutagenic activity of quercetin in the absence of the S9 mix. At lower levels of tyrosinase, activity was restored by incorporation of the S9 mix. It is proposed that the S9 mix enhances the mutagenic activity of quercetin by scavenging superoxide radicals, thus inhibiting the autoxidation of quercetin, and possibly by reducing quinone oxidation products of quercetin. The mutagenic activity of quercetin increased substantially when the pH of the media was decreased. This may be due in part to a decrease in ionization of quercetin at lower pH, thereby increasing its absorption by the tester strain, to a decrease in the rate of autoxidation of quercetin at lower pH, or to a combination of these.

Antioxidants↗
PubMed2005

Enhanced diltiazem bioavailability after oral administration of diltiazem with quercetin to rabbits.

The aim of this study was to investigate the effect of quercetin on the bioavailability of diltiazem after administering diltiazem (15 mg/kg) orally to rabbits either co-administered or pretreated with quercetin (2, 10, 20 mg/kg). The plasma concentrations of diltiazem in the rabbits pretreated with quercetin were increased significantly (p<0.05, at 2 mg/kg; p<0.01, at 10 and 20 mg/kg) compared with the control, but the plasma concentrations of diltiazem co-administered with quercetin were not significant. The areas under the plasma concentration-time curve (AUC) and the peak concentrations (Cmax) of the diltiazem in the rabbits pretreated with quercetin were significantly higher (p<0.05, at 2 mg/kg; p<0.01, at 10 and 20 mg/kg) than the control. The absolute bioavailability (AB%) of diltiazem in the rabbits pretreated with quercetin was significantly (p<0.05 at 2 mg/kg, p<0.01 at 10 and 20 mg/kg) higher (9.10-12.81%) than the control (4.64%). AUC, AB% and Cmax of diltiazem co-administered with quercetin were higher than the control, but these were not significant. The bioavailibility of diltiazem in the rabbits pretreated with quercetin is increased significantly compared with the control, but not in the rabbits co-administered with quercetin. The increased bioavailability of diltiazem in the rabbits pretreated with quercetin might have been resulted result from the quercetin, which inhibits the efflux pump P-glycoprotein and the first-pass metabolizing enzyme CYP 3A4.

Animals↗
PubMed2005

Co-administration of quercetin and catechin in rats alters their absorption but not their metabolism.

Quercetin and catechin are among the major flavonoids in plant foods and their intake has been associated to a risk reduction in several degenerative diseases. The aim of the present study was to bring data on the bioavailability of quercetin and catechin when administered simultaneously. The study was performed on rats adapted to diets containing (i) 0.25% quercetin, or (ii) 0.25% catechin, or (iii) 0.25% quercetin+0.25% catechin. Quercetin, catechin and their metabolites were determined in plasma, urine and liver by HPLC with UV or coulometric detection. When quercetin and catechin were fed in association, their respective plasma concentration significantly decreased (-35% and -28% respectively), whereas the urinary and hepatic concentrations were only affected for quercetin (-36%). These data may be explained by a competitive interaction between quercetin and catechin at the digestive level, leading to a reduction of the intestinal absorption of quercetin and a possible delaying of catechin absorption over time. The simultaneous administration of quercetin and catechin had no effect on the formation of their glucurono and sulfo conjugates, indicating the absence of competition between quercetin and catechin for the corresponding conjugative enzymes.

Animal Feed↗
PubMed2006

Protective effect of quercetin, a natural flavonoid against neuronal damage after transient global cerebral ischemia.

Previous studies have demonstrated that quercetin, a bioflavonoid shows the inhibitory effect against ischemia and reperfusion-induced injury in various tissues including neural tissue. Quercetin is also reported to have an inhibitory effect against matrix metalloproteinases (MMPs). Because MMPs are known to play a main role in the pathophysiology of brain ischemic insult, their mechanisms of possible protective effect of quercetin against brain ischemia remain to be clarified. In the present study, C57BL/6 mice were subjected to 20 min transient global brain ischemia. Cerebral blood flow was monitored by laser doppler flowmeter. Animals were sacrificed 72 h after ischemia. Quercetin (50 mg/kg, dissolved in saline) was intraperitoneally administered to mice at 30 min before and immediately after ischemia and from the second day, quercetin was then administered once daily until sacrifice. The present study was undertaken to test the effect of quercetin on neuronal damage after transient cerebral ischemia. Neuronal damages were remarkable in the medial portion of CA1 and CA2 areas after ischemic insult. In quercetin-treated mice, delayed neuronal damage was significantly decreased compared with vehicle-treated mice. Mice treated with quercetin showed attenuated brain MMP-9 activity. Gelatin gel zymography showed an induction of MMP-9 protein after ischemia. Quercetin significantly inhibited ischemia-induced elevation of MMP-9. In situ zymography showed elevations in gelatinase activities after brain ischemia. Quercetin also inhibited TdT-mediated dUTP nick end labeling (TUNEL) staining in CA1 and CA2 areas. These results demonstrate that quercetin, a natural flavonoid reduces global ischemia-induced neuronal damage through inhibition of MMP-9 activity.

Animals↗
PubMed1998

Transport of quercetin and its glucosides across human intestinal epithelial Caco-2 cells.

There is mounting evidence from human epidemiological, animal in vivo, and in vitro studies to suggest beneficial effects related to the consumption of quercetin and its glucosides. However, there is limited knowledge on the oral bioavailability of these natural products. This study examined the intestinal epithelial membrane transport of quercetin, quercetin 4'-glucoside, and quercetin 3,4'-diglucoside, using the Caco-2 human colonic cell line, a model of human intestinal absorption. The apparent permeability (Papp) of each agent was measured in both apical to basal and basal to apical directions. The apical to basolateral flux of quercetin, Papp 5.8 +/- 1.1 x 10(-6) cm x sec(-1) (mean +/- SEM), was more than 10-fold higher than for the paracellular transport marker mannitol, 0.48 +/- 0.09 x 10(-6) cm x sec(-1) (P < 0.01). Under identical conditions, the Papp for the transcellular marker propranolol was about 5-fold higher than for quercetin (P < 0.001). Interestingly, the reverse, basolateral to apical, flux of quercetin (Papp 11.1 +/- 1.2 x 10(-6) cm x sec(-1)) was almost 2-fold higher than the apical to basolateral flux (P < 0.001). In similar experiments, quercetin 4'-glucoside demonstrated no absorption, Papp < 0.02 x 10(-6) cm x sec(-1) in the apical to basal direction, but did demonstrate basal to apical flux, Papp 1.6 +/- 0.2 x 10(-6) cm x sec(-1). Quercetin 3,4'-diglucoside showed a low apical to basolateral transport (Papp 0.09 +/- 0.03 x 10(-6) cm x sec(-1)); its reverse, basolateral to apical, transport was, however, 4-fold higher (P < 0.05). In these cells, glucose was actively transported with an apical to basolateral Papp of 36.8 +/- 1.1 x 10(-6) cm x sec(-1). These observations suggest facile absorption of quercetin through the human intestinal epithelium, but contrary to a previous proposal, they do not support an active transport process for quercetin glucosides.

Caco-2 Cells↗
PubMed1996

Dissociation of phospholamban regulation of cardiac sarcoplasmic reticulum Ca2+ATPase by quercetin.

Quercetin had a biphasic effect on Ca2+ uptake and calcium-stimulated ATP hydrolysis in isolated cardiac sarcoplasmic reticulum (SR). Stimulation of Ca2+ATPase was observed at low quercetin concentrations (<25 microM) followed by inhibition at higher concentrations. The effects were dependent upon the SR protein concentration, the MgATP concentration, and intact phospholamban regulation of cardiac Ca2+ATPase. Only the inhibitory effects at higher quercetin concentrations were observed in skeletal muscle SR which lacks phospholamban and in cardiac SR treated to remove phospholamban regulation. Stimulation was additive with monoclonal antibody 1D11 (directed against phospholamban) at submaximal antibody concentrations; however, the maximal antibody and quercetin stimulation were identical. Quercetin increased the calcium sensitivity of the Ca2+ATPase like that observed with phosphorylation of phospholamban or treatment with monoclonal antibody 1D11. In addition, low concentrations of quercetin increased the steady-state formation of phosphoenzyme from ATP or Pi, but higher quercetin decreased phosphoenzyme levels. Quercetin, even under stimulatory conditions, was a competitive inhibitor of ATP, but appears to relieve the Ca2+ATPase from phospholamban inhibition, thereby, producing an activation. The subsequent inhibitory action of higher quercetin concentrations results from competition of quercetin with the nucleotide binding site of the Ca2+ATPase. The data suggest that quercetin interacts with the nucleotide binding site to mask phospholamban's inhibition of the SR Ca2+ATPase and suggests that phospholamban may interact at or near the nucleotide binding site.

Animals↗
PubMed2006

Rat gastrointestinal tissues metabolize quercetin.

Quercetin and quercetin glycosides from food or dietary supplements appear in body tissues almost exclusively as glucuronated, sulfated, and methylated quercetin conjugates, suggesting that the in vivo bioactivity of quercetin may be due to its metabolites. In this study, pre- and postabsorptive metabolism of orally ingested quercetin was examined by comparing the metabolite pattern in gastrointestinal (GI) tissues, contents, and internal tissues. F344 rats (n = 6) were fed for 6 wk a diet containing 0.45% quercetin and the metabolite patterns were determined in the tissues and contents of stomach, small intestine, cecum, and colon and in liver, kidney, and plasma using LC-MS/MS. GI contents contained predominantly unmetabolized quercetin at 94-100%, whereas quercetin in GI tissues was present as 11 different sulfated, glucuronated, and methylated metabolites at 32% in stomach, 88% in small intestine, 27% in cecum, and 46% in colon. Quercetin was further metabolized postabsorption and found in liver, kidney, and plasma almost exclusively as sulfated methyl-quercetin glucuronide. The unique pattern of quercetin metabolites in each GI tissue indicates extensive biotransformation before absorption and distribution in rats.

Administration, Oral↗
PubMed1998

Extensive binding of the bioflavonoid quercetin to human plasma proteins.

Although the bioflavonoids, a large group of polyphenolic natural products, exert chemopreventive effects in cardiovascular disease and cancer, there is little information about the disposition of these dietary components in man. The objective of this study was to investigate the plasma-protein binding of the most abundant bioflavonoid, quercetin, using 14C-labelled quercetin. An ultracentrifugation assay (170,000 g for 16 h at 20 degrees C) was shown to sediment plasma proteins. Binding of quercetin to normal plasma was extensive (99.1+/-0.5%, mean +/- s.d., n = 5). The unbound fraction varied as much as 6-fold, 0.3-1.8%, between subjects. This high binding was independent of quercetin concentration over the range 1.5-15 microM (0.5-5 microg mL(-1)). Human serum albumin was the primary protein responsible for the binding of quercetin in plasma (99.4+/-0.1%). Binding by alpha1-acid glycoprotein (39.2+/-0.5%) and very-low-density lipoproteins (<0.5% of total quercetin) did not make substantial contributions to overall plasma binding. The equilibrium association constant for the binding of quercetin to serum albumin was 267+/-33 x 10(3) M(-1) (n = 15). Thermodynamic data for the binding of quercetin to serum albumin indicated spontaneous, endothermic association. Displacement studies suggested that in man the 'IIA' subdomain binding site of human serum albumin was the primary binding site for quercetin. Association of quercetin with erythrocytes was significantly (P < 0.001) reduced by plasma protein binding. These data indicate poor cellular availability of quercetin because of its extensive binding to plasma proteins.

Blood Proteins↗
PubMed1998

Dietary flavonol quercetin induces chloride secretion in rat colon.

The aim of this study was to investigate the possible effects of the flavonol quercetin, the most abundant dietary flavonoid, on the intestinal mucosa. In vitro experiments were performed with various segments of the rat intestine, using the Ussing chamber technique. Quercetin increased the short-circuit current (Isc) in the jejunum, ileum, and proximal and distal colon. Additional experiments were performed using preparations of the proximal colon. The maximum effective dose of quercetin was found to be approximately 100 microM. The quercetin-induced increase in Isc was inhibited by the Cl- channel blocker 5-nitro-2-(3-phenylpropylamino)-benzoic acid. Adding blockers of the Na+-K+-2Cl- cotransporter to the serosal compartment diminished the increase of Isc due to quercetin. Ion substitution and flux measurements indicated that the effect of quercetin was due to electrogenic Cl- and HCO-3 secretion. In contrast to the aglycone, the quercetin glycoside rutin had no effect. The effect of quercetin on Isc was additive to the Isc increase induced by forskolin, but the flavonoid diminished the Isc evoked by carbachol. The phosphodiesterase inhibitor theophylline blocked the effect of quercetin. Genistein, a related isoflavone, did not alter the Isc evoked by quercetin. These findings demonstrate that the dietary flavonol quercetin induces Cl- secretion and most likely HCO-3 secretion in rat small and large intestine. The effects are restricted to the flavonol aglycone.

Administration, Oral↗
PubMed2005

Absorption of quercetin and rutin in rat small intestine.

BACKGROUND/AIMS: Dietary antioxidant flavonoids, especially flavonols, are ubiquitous constituents of plant foods with potential health-promoting effects. However, the actual bioavailability of these compounds in vivo, especially in the prevalent glycosidic form, remains a controversial point in making an assessment of their biological importance. Thus, absorption of quercetin and rutin in the small intestine has been determined. METHODS: The bioavailability of quercetin and rutin (quercetin-3-rutinoside) was assessed in vivo, with single-meal experiments with rats and by an in vitro method with ligated loops of rat small intestine. The amount of quercetin or rutin in the plasma of rats or in the lumen of each intestinal segment was assayed by maximum absorption in the UV/VIS optical spectrum as was the amount of compound that had crossed the gut wall into the incubation buffer. In addition, uptake of [14C]quercetin was tested in vitro. RESULTS: Absorption of both quercetin and rutin from the small intestine of rat was evident. However, rutin appeared to be absorbed more slowly than quercetin. Experiments with [14C]quercetin showed that only 1.5% quercetin crossed the gut wall in vitro and more than half of the total quercetin was bound to the small intestinal tissue. CONCLUSIONS: Both quercetin and rutin can attach to and traverse the small intestine of the rat. Binding of flavonoids to the intestinal wall components may however greatly limit their absorption from the small intestine.

Animals↗
PubMed2006

Regulation of intracellular calcium levels and urokinase activity in MDA MB 231 cells by quercetin.

BACKGROUND: The common plant bioflavonoid, quercetin, is cytotoxic to various tumor cell lines, particularly breast cancer, by affecting the protein-kinase-C-dependent signal pathways and by cell cycle regulation. However, its role in breast cancer metastasis has not been studied so far. Increased uPA activity is evident in highly metastatic breast cancer, which is calcium dependent. METHODS: MDA MB 231 cells were treated with various concentrations of quercetin (15-45 microg/ml). The cytotoxic effect of quercetin was assessed by MTT assay and DNA fragmentation analysis. Intracellular calcium levels were measured using Fura-2, a specific Ca2+ fluorescence indicator. Calcium uptake and release in cells treated with quercetin were measured using radioactive 45Ca2+. Urokinase enzyme activity was assayed by a casein zymogram. RESULTS: Quercetin elicited dose- and time-dependent cytotoxicity as evidenced by the MTT assay. The maximum effect was observed at 48 h with a quercetin concentration of (45 microg/ml). DNA agarose gel electrophoresis showed dose-dependent DNA fragmentation on quercetin treatment. Quercetin caused significant depletion of cytosolic calcium levels and decreased calcium uptake from the intracellular stores. Casein zymogram showed a marked reduction of urokinase activity as evident by clear lysis bands on a dark background on treatment with quercetin. CONCLUSION: Quercetin was found to exhibit cytotoxicity in the highly invasive breast cancer cell line MDA MB 231 in a dose- and time-dependent manner. Quercetin inhibited calcium dependent urokinase activity and hence may prove to be an effective antimetastatic agent.

Adenocarcinoma↗
PubMed1999

Quercetin inhibits benzo[a]pyrene-induced DNA adducts in human Hep G2 cells by altering cytochrome P-450 1A1 gene expression.

Quercetin is one of the most abundant of the naturally occurring flavonoids. It has been estimated that about 25-50 mg of quercetin are consumed from the daily diet. The chemopreventive effect of quercetin on dietary carcinogen has been intensely studied in animal models; however, knowledge regarding the molecular mechanism is still limited. In this study, the human hepatoma Hep G2 cell line was used to investigate how quercetin prevents benzo[a]pyrene (B[a]P)-induced DNA adducts. The Hep G2 cells were treated with 10 microM B[a]P for 18 hours in the presence or absence of quercetin. The DNA adduct levels, evaluated by 32P postlabeling, decreased in a dose-dependent manner after treatment with quercetin. Cytochrome P-450 1A1 (CYP1A1) and glutathione S-transferase involvement have been well demonstrated in the modulation of B[a]P-induced DNA damage. From the assays of both enzyme activities, quercetin inhibits CYP1A1-linked ethoxyresorufin O-dealkylase activity more effectively than glutathione S-transferase activity. To elucidate the molecular mechanisms, reverse transcriptase-polymerase chain reaction and Western blot were used to evaluate whether the decrease in CYP1A1 enzyme activity by quercetin is mediated because of alterations of CYP1A1 transcription or mRNA stability. The results indicated that quercetin significantly inhibits B[a]P-induced CYP1A1 mRNA and protein expression. From these findings, we conclude that quercetin suppresses B[a]P-induced DNA damage in human Hep G2 cells by altering CYP1A1 gene expression. Thus we suggest that dietary quercetin may have a long-term preventive effect on chemical carcinogenesis, especially in people who eat a diet rich in fruits and vegetables.

Anticarcinogenic Agents↗
PubMed2002

Effect of quercetin and its conjugated metabolite on the hydrogen peroxide-induced intracellular production of reactive oxygen species in mouse fibroblasts.

To clarify the antioxidative role of quercetin metabolites in cellular oxidative stress, we measured the inhibitory effects of the quercetin aglycon and quercetin 3-O-beta-D-glucuronide (Q3GA), which is one of the quercetin metabolites in the blood after an intake of quercetin-rich food, on the production of hydrogen peroxide (H2O2)-induced intracellular reactive oxygen species in mouse fibroblast 3T3 cultured cells. When the cells were exposed to H2O2 in the presence of quercetin or Q3GA, Q3GA was found to be less effective than quercetin. In the case of a pretreatment with quercetin or Q3GA before the exposure, Q3GA, but not the quercetin aglycon, exerted an inhibitory effect, although its cellular uptake was unlikely. The quercetin aglycon appeared to fail in its antioxidative effect due to metabolic conversion into isorhamnetin conjugates, with substantial oxidative degradation resulting from the pretreatment. It is, therefore, suggested that quercetin metabolites take part in the protection of intracellular oxidative stress induced by the extraneous attack of H2O2.

3T3 Cells↗