Quercetin

302.24

302.24

204-187-1

9IKM0I5T1E

9219

2811

DTXSID4021218

C792

Yellow needles (dilute alcohol, +2 water)

29329990

127

1.5

Quercetin appears as yellow needles or yellow powder. Converts to anhydrous form at 203-207°F. Alcoholic solutions taste very bitter. (NTP, 1992)

1.3616 (rough estimate)

316.5 °C

Sublimes

248.1±25.0 °C

1.4790 (estimate)

H2O: <0.1 g/100 mL at 21 ºC

Store at 0-5°C

2.81X10-14 mm Hg at 25 deg C (est)

LD50 oral in rat: 161mg/kg

Henry's Law constant = 6.60X10-21 atm-cu m/mol at 25 °C (est)

pKa1 = 7.17 (phenol); pKa2 = 8.26 (phenol); pKa3 = 10.13 (phenol); pKa4 = 12.30 (phenol); pKa5 = 13.11 (phenol) (est)

166.7 Ų [M+H]+ [CCS Type: DT, Method: single field calibrated with Agilent tune mix (Agilent)]|158.98 Ų [M-H]- [CCS Type: DT, Method: single field calibrated with Agilent tune mix (Agilent)]|163.4 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]

Yellow needles from dil alcohol. Becomes anhydrous at 95-97 °C. When anhydrous, decomposes at 314 °C; uv max (alcohol) 258, 375 nm (log epsilon 2.75, 2.75). One gram dissolves in 290 mL absolute alcohol, in 25 mL boiling alcohol. Soluble in glacial acetic acid; in aqueous alkaline solutions with yellow color. Practically insoluble in water. Alcoholic solutions taste very bitter. /Dihydrate/|Crystals; mp 123-125 °C; UV max (chloroform): 249, 343 nm (log epsilon 4.43, 4.14) /Pentabenzyl ether/|Hydroxyl radical reaction rate constant = 2.39X10-10 cu cm/molec-sec at 25 °C (est)|Ozone reaction rate constant = 1.05X10-16 cu cm/molec-sec at 25 °C (est)

Sensitive to exposure to air and light. Insoluble in water.

Ketones

QUERCETIN is a strong antioxidant and a metal chelator. Promotes the formation of nitrosamines (NTP, 1992).

III

6.1(b)

2811

3

25-36/37/38

45-36-26

LK8750000

T,Xi

Stable under normal temperatures and pressures.

P301 + P310 + P330

H301

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

DHHS/NTP; Toxicology & Carcinogenesis Studies of Quercetin in F344/N Rats (Feed Studies) Technical Report Series No. 409 (1992) NIH Publication No 92-3140

Flash point data for this compound are not available; however, it is probably combustible. (NTP, 1992)

|Danger|H301 (64.75%): Toxic if swallowed [Danger Acute toxicity, oral]|P264, P270, P301+P310, P301+P312, P321, P330, P405, and P501|Aggregated GHS information provided by 264 companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Fires involving this compound may be controlled with a dry chemical, carbon dioxide or Halon extinguisher. (NTP, 1992)

Excerpt from ERG Guide 154 [Substances - Toxic and/or Corrosive (Non-Combustible)]: As an immediate precautionary measure, isolate spill or leak area in all directions for at least 50 meters (150 feet) for liquids and at least 25 meters (75 feet) for solids. SPILL: Increase, in the downwind direction, as necessary, the isolation distance shown above. FIRE: If tank, rail car or tank truck is involved in a fire, ISOLATE for 800 meters (1/2 mile) in all directions; also, consider initial evacuation for 800 meters (1/2 mile) in all directions. (ERG, 2016)

SMALL SPILLS AND LEAKAGE: Should a spill occur while you are handling this chemical, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with 60-70% ethanol and transfer the dampened material to a suitable container. Use absorbent paper dampened with 60-70% ethanol to pick up any remaining material. Seal the absorbent paper, and any of your clothes, which may be contaminated, in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with 60-70% ethanol followed by washing with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned. STORAGE PRECAUTIONS: You should protect this chemical from exposure to light. Keep the container tightly closed under an inert atmosphere, and store under refrigerated temperatures. (NTP, 1992)

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with a combination filter cartridge, i.e. organic vapor/acid gas/HEPA (specific for organic vapors, HCl, acid gas, SO2 and a high efficiency particulate filter). (NTP, 1992)

Quercetin is a flavanoid component of hardwood wood dust(1). It is found in leaf tobacco(2) and tea leaves(3).

Quercetin supplements have not been linked serum aminotransferase elevations during therapy, although there have been few focused studies of its hepatic safety. Furthermore, there have been no published reports of clinically apparent liver injury attributable to quercetin. Indeed, many in vitro and in vivo studies have shown that quercetin protects against hepatic injury caused by drugs and toxins including acetaminophen and cancer chemotherapeutic agents. These hepatoprotective effects have not been demonstrated in prospective clinical trials in humans.

In human myelogenous leukemia cells, quercetin was reported to arrest growth of the cell by an incr in the uptake of vincristine, a chemotherapeutic agent.|Quercetin binds, in vitro, to the DNA gyrase site in bacteria. Therefore, theoretically, it can serve as a competitive inhibitor to the quinolone antibiotics which also bind to this site ... Because of the theoretical risk of genotoxicity in normal tissues in those using cisplatin along with quercetin, those using cisplatin should avoid quercetin supplements ... Bromelain and papain are reported to incr absorption of quercetin.|Quercetin has a pro-oxidant effect and will incr the iron-dependent DNA damage induced by bleomycin. Quercetin may reduce iron to the ferrous state, which allows bleomycin to complex more readily with oxygen and produce more efficient DNA damage. A biphasic pro-oxidant effect with bleomycin has been demonstrated. At low concn incr DNA damage was noted, and at higher doses less DNA damage was noted.|Concomitant use may reduce cyclosporine /or floroquinolones/ effectiveness.|For more Interactions (Complete) data for QUERCETIN (18 total), please visit the HSDB record page.

LD50 Rat oral 161 mg/kg|LD50 Mouse iv 18 mg/kg|LD50 Mouse oral 160 mg/kg|LD50 Mouse sc 100 mg/kg

... The NTP 2-year studies were conducted by admin 0, 1,000, 10,000, or 40,000 ppm quercetin (>95% pure) in feed to groups of 50 male and female rats for 104 wk. Ten additional animals per dose group were evaluated at 6 and 15 mo ... Body weights of exposed male and female rats given 1,000 and 10,000 ppm were within 5% of controls throughout the studies. Reduced body weight gain in male and female rats receiving 40,000 ppm was observed by wk 15 and the final mean body weights were 87% of controls at wk 104. Survival and feed consumption were similar among exposed and control groups throughout the studies. The average amt of quercetin consumed per day by the 1,000, 10,000 and 40,000 ppm dose groups after wk 52 were 40, 400, and 1,900 mg/kg of body weight ... In male rats, the principal toxic effects associated with the dietary admin of quercetin for 2 yr were observed in the kidney. There were dose-related incr in the severity of chronic nephropathy (control, 2.7; low-dose, 2.7; mid-dose, 3.0; high-dose, 3.2) and a slight incr incidence in focal hyperplasia of the renal tubule epithelium (1/50; 2/50; 3/50; 4/50). Parathyroid hyperplasia, indicative of renal secondary hyperparathyroidism, also incr incidence in dosed male rats (1/43, 6/45, 6/43, 17/43). The evaluation of single sections from the left and right kidneys revealed renal tubule adenomas in 3 male rats and adenocarcinomas in another male rat receiving 40,000 ppm quercetin; none were seen in the controls. Examination of additional step sections of the male rat kidney identified additional hyperplasia and adenomas in all dose groups (hyperplasia: 2/50, 2/50, 6/50, 8/50; adenoma: 1/50, 2/50, 7/50, 6/50). The overall incidence of renal tubule adenoma or adenocarcinoma combined in male rats was 1/50 in controls and 9/50 in the high-dose group. There was a statistically significant, dose-related decr in the incidence of mammary gland fibro-adenomas in exposed female rats (29/50, 27/50, 16/50, 9/50), which may in part be attributed to lower body weight gains. There was a treatment-related accumulation of yellow-brown granular pigment adsorbed to or absorbed by the epithelial cells of the glandular stomach, ileum, jejunum, and, to a lesser extent, the duodenum and colon. The severity of the pigmentation in these tissues incr with incr length of exposure. There were no other lesions considered to be related to chemical admin ... Conclusions: Under the conditions of these 2 year feed studies there was some evidence of carcinogenic activity of quercetin in male F344/N rats based on an increased incidence of renal tubule cell adenomas. There was no evidence of carcinogenic activity of quercetin in female F344/N rats receiving 1,000, 10,000 or 40,000 ppm.

Precautions: Because of lack of long-term safety data, quercetin should be avoided by pregnant women and nursing mothers.

Quercetin is the aglucon of quercitrin, of rutin, and other glycosides. It is widely distributed in the plant kingdom, especially in rinds and barks, in clover blossoms, and ragweed pollen and has been isolated from Rhododendron cinnabarinum Hook, Ericaceae(1)|Quercetin is widely distributed in the plant kingdom, where it occurs as a condensation product (a glycoside) with sugars ... Plants /that/ contain these glycosides are: Allium ascalonicum; Allium cepa (onion); Allium porrum (leek); Anethum graveolens; Apium graveolens; Asperagus officinalis (asparagus); Brassica chinensis; Brassica napus; Brassica oleracae var. butrytis subvar. cymosa; Brassica oleraceae var. buttata; Brassica oleraceae var. captata; Brassica oleraceae var. gemmifera (plants of cabbage and mustard); Capsicum annuum (ornamental pepper); Cichorium endivia (endive); Citrus paradisi (grapefruit); Fragaria ananassa; Humulus lupulus; Latuca sativa (lettuce); Malus pumila (apple); Malus silvestris; Mangifera indica (mango); Petroselinum crispum; Prunus armeniaca; Prunus avium; Prunus domestica (European plum); Raphanus sativus (radish); Rheum spp; Ribes L.; Ribes nigrum (blackcurrant); Ribes grossularia; Rubus L.; Rubus ideaus; Rumex acetosa; Sambuccus nigra (elder); Solanum tuberosum (potato); Solanum lycopersicum; Spinacea oleraceae (spinach); Vaccinium macrocarpum ... Quercetin has been isolated from grapes, Vitis vinifera (1.4 mg/kg, fresh fruit), from leaves of the 'huckleberry', Vaccinium myrtillus (11 g/kg, dry weight, for quercetin and its glucosides), and from the leaves of Rhododendron cinnabarinum Hook. ... China tea, Camellia sinensis, has been reported to contain relatively large amounts of triglycosides of quercetin ... The total concentration of kaempferol and quercetin glycosides in tea (unspecified variety) is >10,000 mg/kg. ... This compound occurs in bracken fern (Pteridium aquilinum) ... .

Quercetin's production and use as an experimental antioxidant dietary supplement(1), cosmetic preservative(2), and natural dye(3) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 460(SRC), determined from a water solubility of 60 mg/L(2) and a regression-derived equation(3), indicates that quercetin is expected to have moderate mobility in soil(SRC). The estimated pKas of quercetin are 7.17, 8.26, 10.13, 12,30, and 13.11(4), indicating that this compound will partially exist in the anion form in the environment at neutral pH and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(5). Volatilization of quercetin from moist soil surfaces is not expected to be an important fate process because it is an anion and anions do not volatilize(SRC). Quercetin is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.8X10-14 mm Hg(SRC), determined from a fragment constant method(6). Quercetin's rapid degradation in soil(7) suggests that biodegradation may be an important environmental fate process(SRC).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 460(SRC), determined from a water solubility of 60 mg/L(2) and a regression-derived equation(3), indicates that quercetin is not expected to adsorb to suspended solids and sediment(SRC). The estimated pKas of 7.17, 8.26, 10.13, 12,30, and 13.11(4) indicate quercetin will exist partially in the anion form at pH values of 5 to 9 and therefore volatilization from water surfaces is not expected to be an important fate process(5). According to a classification scheme(6), an estimated BCF of 61(SRC), from its water solubility(2) and a regression-derived equation(3), suggests the potential for bioconcentration in aquatic organisms is moderate(SRC). Quercetin's rapid degradation in soil(7) suggests that biodegradation may be an important environmental fate process in water(SRC).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), quercetin, which has an estimated vapor pressure of 2.8X10-14 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase quercetin may be removed from the air by wet or dry deposition(SRC). Quercetin contains chromophores that absorb at wavelengths >290 nm(4) and therefore may be susceptible to direct photolysis by sunlight(SRC).

Quercetin is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(1). Quercetin contains chromophores that absorb at wavelengths >290 nm(1) and therefore may be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 61 was calculated in fish for quercetin(SRC), using a water solubility of 60 mg/L(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is moderate(SRC), provided the compound is not metabolized by the organism(SRC).

The Koc of quercetin is estimated as 460(SRC), using a water solubility of 60 mg/L(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that quercetin is expected to have moderate mobility in soil. The estimated pKas of quercetin are 7.17, 8.26, 10.13, 12,30, and 13.11(4), indicating that this compound will partially exist in the anion form in the environment at neutral pH and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(5).

The estimated pKas of 7.17, 8.26, 10.13, 12,30, and 13.11(1) indicate quercetin will partially exist anion form at pH values of 5 to 9 and therefore volatilization from water surfaces is not expected to be an important fate process(2). Volatilization of quercetin from moist soil surfaces is not expected to be an important fate process because it is an anion and anions do not volatilize(SRC). Quercetin is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.8X10-14 mm Hg(SRC), determined from a fragment constant method(3).

Occupational exposure to quercetin may occur through inhalation and dermal contact with this compound at workplaces where quercetin is produced or used. Use data indicate that the general population may be exposed to quercetin via dermal contact with this compound or other consumer products containing quercetin. (SRC)

Quercetin is a flavonoid found in many foods and herbs and is a regular component of a normal diet. Extracts of quercetin have been used to treat or prevent diverse conditions including cardiovascular disease, hypercholesterolemia, rheumatic diseases, infections and cancer but have not been shown to be effective in clinical trials for any medical condition. Quercetin as a nutritional supplement is well tolerated and has not been linked to serum enzyme elevations or to episodes of clinically apparent liver injury.

Herbal and Dietary Supplements

Quercetin has been used in medicine to decrease capillary fragility.|/EXPL THER/ ... In a randomized, double-blind, placebo-controlled trial ... /among patients with category III chronic prostatitis syndromes (nonbacterial chronic prostatitis and prostatodynia)/ ... Significant improvement was achieved in the treated group, as measured by the NIH chronic prostatitis score. Some 67% of the treated subjects had at least 25% improvement in symptoms, compared with 20% of the placebo group achieving this same level of improvement. In a follow up, unblind, open-label study ... quercetin was combined with bromelain and papain, which may enhance its absorption. In this study, 82% achieved a minimum 25% improvement score.|/EXPL THER/ Lymphocyte protein kinase phosphorylation was inhibited by quercetin in 9 of 11 cancer patients in a phase I clinical trial. Fifty-one patients with microscopically confirmed cancer not amenable to standard therapies and with a life expectancy of at least 12 wk participated in this trial ... The patients were treated at 3-wk intervals at the beginning of the study. Quercetin was admin iv as quercetin dihydrate ... The max allowed dose was reached when 2 of 3 patients on each dose schedule reached grade 3 or 4 general toxicity, or grad 2 renal toxicity, cardiac toxicity, or neurotoxicity. Phosphorylation was inhibited at 1 hr and persisted for 16 hr. In one patient with ovarian cancer refractory to cisplatin, cancer antigen-125 (CA 125) fell from 295 to 55 units/mL after treatment with 2 courses of quercetin ... A hepatoma patient had serum alpha-fetoprotein fall.|/EXPL THER/ ... Quercetin was reported to inhibit tumor necrosis factor-alpha (TNF-alpha) overproduction and attenuate pathophysiological conditions during acute and chronic inflammation ... In asthma, the activation of mast cells and basophils by allergen releases chemical mediators and synthesizeds cytokines leading to inflammatory conditions ... Quercetin was reported to inhibit cytokine expression and synthesis by human basophils ... A metabolite of quercetin, 3-O-methylquercetin (3-MQ), was reported to provide beneficial effects on asthma by inhibiting cAMP- and cGMP-phosphodiesterase (PDE). ...

Although quercetin seems to have potential as an anticancer agent, future studies are needed, because most studies are based on in vitro experiments using high concn of quercetin unachievable by dietary ingestion, and because its beneficial effects on cancer are still inconclusive in animal and/or human studies.|... Quercetin has been shown to protect low density lipoprotein (LDL) from oxidation and prevent platelet aggregation. It was also reported to inhibit the proliferation and migration of smooth muscle cells ... Quercetin was reported to significantly lower the plasma lipid, lipoprotein and hepatic cholesterol levels, inhibit the production of oxLDL produced by oxidative stress, and protect an enzyme, which can hydrolyzed specific lipid peroxides in oxidized lipoproteins and in atherosclerotic lesions ... /It/ induced endothelium-dependent vasorelaxation in rat aorta via incr nitric oxide production ... Quercetin and its glycosides were also reported to inhibit the angiotensin-converting enzyme activity, and ANG II-induced JNK activation inducing vascular smooth muscle cell (VSMC) hypertrophy ... However, some effects may not be feasible or negligible in physiological conditions, because concn of quercetin in most studies are too high to be achieved by dietary ingestion ... and beneficial effects of quercetin on cardiovascular diseases are still inconclusive in human studies ...

Naturally occurring or synthetic substances that inhibit or retard oxidation reactions. They counteract the damaging effects of oxidation in animal tissues. (See all compounds classified as Antioxidants.)

After oral administration of a single dose of 4 g quercetin to four male and two female volunteers, neither quercetin nor its conjugates was detected in the blood or urine during the first 24 hr; 53% of the dose was recovered in the feces within 72 hr. After a single intravenous injection of 100 mg quercetin to six volunteers, the blood plasma levels declined biphasically, with half-lives of 8.8 min and 2.4 hr; protein binding exceeded 98%. In the urine, 0.65% of the intravenous dose was excreted as unchanged quercetin and 7.4% as a conjugate within 9 hr; no further excretion occurred up to 24 hr ...|When 14C-quercetin was administered orally to ACI rats, about 20% of the administered dose was absorbed from the digestive tract, more than 30% was decomposed to yield 14-CO2 & about 30% was excreted unchanged in feces..|One male and one female volunteer were given a diet containing quercetin glucosides (64.2 mg expressed as the aglycone). The mean peak plasma concentration of quercetin was 196 ng/mL which was reached 2.9 hr after ingestion. The time-course of the plasma concentration of quercetin was biphasic, with half-lives of 3.8 hr for the distribution phase and 16.8 hr for the elimination phase. Quercetin was still present in plasma 48 hr after ingestion ... /Quercetin glucosides/|Autoradiographic analysis of a fasted rat 3 hr after administration of a single oral dose of 2.3 mg/kg (4-(14)C)quercetin showed that although most of the radiolabel remained in the digestive tract it also occurred in blood, liver, kidney, lung and ribs. After oral administration of 630 mg/kg of the labelled compound to rats, 34% of the radiolabel excreted within 24 hr ... was expired carbon dioxide, 12% in bile and 9% in urine; within 48 hr, 45% was recovered in the feces. Approximately 60% of the radiolabel in the feces was identified as unmetabolized quercetin ...|For more Absorption, Distribution and Excretion (Complete) data for QUERCETIN (9 total), please visit the HSDB record page.

The glycosides are hydrolyzed in the body to corresponding aglycones, which are then further metabolized by scission of the heterocyclic ring to give 3,4-dihydroxy-phenyl-substituted acids ... The site of ring scission depends on structure ... with flavonols (quercetin) scission occurs at the 1,2 & 3,4 bonds to yield homoprotocatechuic acid ... These acids are further metabolized by beta-oxidation of acyl side-chain, o-methylation & demethylation, & aromatic dehydroxylation.|o-Beta-hydroxyethylated derivatives of quercetin were isolated from urine samples & separated by HPLC. The 5,7,3',4'-tetra compd was separated from 3,7,3',4'-tetra derivative. The 7,3',4'-tri & 7'-mono compounds gave 1 common peak, separated from the peak for the 7,4'-di compd.|After oral admin to ACI rats, the absorbed (14)C-quercetin was rapidly excreted into the bile & urine within 48 hr as the glucuronide & sulfate conjugates of (14)C-quercetin, 3'-o-monomethyl quercetin & 4'-o-monomethyl quercetin. Efficient metabolism and elimination of quercetin may be one reason for the lack of carcinogenicity in rats.|The metabolites of quercetin flavonols identified in urine samples collected from two male volunteers who consumed their habitual diets for three days were 3,4-dihydroxyphenylacetic acid, meta-hydroxyphenylacetic acid, and 4-hydroxy-3-methoxyphenylacetic acid ...|For more Metabolism/Metabolites (Complete) data for QUERCETIN (10 total), please visit the HSDB record page.|Quercetin has known human metabolites that include Dihydroquercetin and Mikwelianin.

One male and one female volunteer were given a diet containing quercetin glucosides (64.2 mg expressed as the aglycone) ... Half-lives /were/ 3.8 hr for the distribution phase and 16.8 hr for the elimination phase ... /Quercetin glucosides/|...The elimination half-life of quercetin is approx 25 hr.

Quercetin is a specific quinone reductase 2 (QR2) inhibitor, an enzyme (along with the human QR1 homolog) which catalyzes metabolism of toxic quinolines. Inhibition of QR2 in plasmodium may potentially cause lethal oxidative stress. The inhibition of antioxidant activity in plasmodium may contribute to killing the malaria causing parasites.|... The 5, 7, 3', 4'-hydroxyl groups on quercetin are capable of donating electrons to quench various radical oxygen species (ROS) and other radical species ... Oxygen radicals (superoxide, hydrogen peroxide, hydroxyl radicals, and other related radicals) ... are quenched by ... antioxidant systems, including antioxidant cmpd, which balance cellular redox status involved in cellular processes for cell homeostasis ... Generally, 3 criteria are considered to assess the antioxidant activity of flavonoids in vitro: first, B ring with 2 hydroxyl groups (adjacent), second, C ring with 2,3-double bond, 4-oxo, and 3-hydroxyl group, and third, A ring with 5,7-dihydroxyl groups. Quercetin meets all 3 criteria, indicating stronger antioxidant activity ... The flavonol was reported to prevent radicals from damaging carbohydrates, proteins, nucleotides, and lipids ... The glucuronide conjugates found in the plasma were also reported to have potent antioxidant activity, indicating that the activity may be retained depending on conjugation positions ...|Cytokines such as tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can induce apoptosis in colon cancer cells through engagement of death receptors. Nevertheless, evading apoptosis induced by anticancer drugs characterizes many types of cancers. This results in the need for combination therapy. In this study ... whether the flavonoid quercetin could sensitize human colon adenocarcinoma cell lines to TRAIL-induced apoptosis /was investigated/ ... Quercetin enhanced TRAIL-induced apoptosis by causing the redistribution of DR4 and DR5 into lipid rafts. Nystatin, a cholesterol-sequestering agent, prevented quercetin-induced clustering of death receptors and sensitization to TRAIL-induced apoptosis in colon adenocarcinoma cells ... Qercetin, in combination with TRAIL, triggered the mitochondrial-dependent death pathway, as shown by Bid cleavage and the release of cytochrome c to the cytosol. Together /the/ findings propose that quercetin, through its ability to redistribute death receptors at the cell surface, facilitates death-inducing signaling complex formation and activation of caspases in response to death receptor stimulation. Based on these results, this study provides a challenging approach to enhance the efficiency of TRAIL-based therapies.|Previously /the authors/ reported that isoflavone (genistein) activated bone sialoprotein (BSP) gene transcription is mediated through an inverted CCAAT box in the proximal BSP gene promoter. The present study investigates the regulation of BSP transcription in a rat osteoblast-like cell line, ROS 17/2.8 cells, by quercetin and its conjugated metabolite quercetin 3-glucuronide. Quercetin and quercetin 3-glucuronide (5 uM) increased the BSP mRNA levels at 12 hr and quercetin upregulated the Cbfa1/Runx2 mRNA expression at 12 hr. From transient transfection assays using various sized BSP promoter-luciferase constructs, quercetin increased the luciferase activity of the construct (pLUC3), including the promoter sequence nucleotides -116 to -43. Transcriptional stimulations by quercetin were almost completely abrogated in the constructs that included 2 bp mutations in the inverted CCAAT and FRE elements whereas the CCAAT-protein complex did not change after stimulation by quercetin according to gel shift assays. Quercetin increased the nuclear protein binding to the FRE and 3'-FRE. These data suggest that quercetin and quercetin 3-glucuronide increased the BSP mRNA expression, and that the inverted CCAAT and FRE elements in the promoter of the BSP gene are required for quercetin induced BSP transcription.|Connexin proteins form gap junctions, which permit direct exchange of cytoplasmic contents between neighboring cells. Evidence indicates that gap junctional intercellular communication (GJIC) is important for maintaining homeostasis and preventing cell transformation. Furthermore, connexins may have independent functions including tumor growth suppression. Most tumors express less connexins, have reduced GJIC and have increased growth rates compared with non-tumorigenic cells. The purpose of this study was to determine whether common flavonoids, genistein and quercetin, increase connexin43 (Cx43) levels, improve GJIC and suppress growth of a metastatic human breast tumor cell line (MDA-MB-231). Quercetin (2.5, 5 ug/mL) and genistein (0.5, 2.5, 15 ug/mL) upregulated Cx43 but failed to increase GJIC. Cx43 localized to the plasma membrane following genistein treatment (2.5, 15 ug/mL). In contrast, Cx43 aggregated in the perinuclear region following quercetin treatment (0.5, 2.5, 5, 15 ug/mL). Both genistein (15 ug/mL) and quercetin (2.5, 5, 15 ug/mL) significantly reduced MDA-MB-231 cell proliferation. In summary, genistein and quercetin increase Cx43 and suppress MDA-MB-231 cell proliferation at physiologically relevant concentrations. These results demonstrate that genistein and quercetin are potential anti-breast cancer agents.|For more Mechanism of Action (Complete) data for QUERCETIN (12 total), please visit the HSDB record page.

ACUTE/CHRONIC HAZARDS: When heated to decomposition this compound emits acrid smoke and irritating fumes. (NTP, 1992)

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop. SKIN: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all affected skin areas thoroughly with soap and water. If symptoms such as redness or irritation develop, IMMEDIATELY call a physician and be prepared to transport the victim to a hospital for treatment. INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. IMMEDIATELY call a physician and be prepared to transport the victim to a hospital even if no symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop. Provide proper respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be used; if not available, use a level of protection greater than or equal to that advised under Protective Clothing. INGESTION: DO NOT INDUCE VOMITING. If the victim is conscious and not convulsing, give 1 or 2 glasses of water to dilute the chemical and IMMEDIATELY call a hospital or poison control center. Be prepared to transport the victim to a hospital if advised by a physician. If the victim is convulsing or unconscious, do not give anything by mouth, ensure that the victim's airway is open and lay the victim on his/her side with the head lower than the body. DO NOT INDUCE VOMITING. IMMEDIATELY transport the victim to a hospital. OTHER: Since this chemical is a known or suspected carcinogen you should contact a physician for advice regarding the possible long term health effects and potential recommendation for medical monitoring. Recommendations from the physician will depend upon the specific compound, its chemical, physical and toxicity properties, the exposure level, length of exposure, and the route of exposure. (NTP, 1992)

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/HUMAN EXPOSURE STUDIES/ ... A double-blind, placebo-controlled study compared one gram daily of oral quercetin with placebo in 27 healthy subjects ... The study continued for 28 days, during which period subjects receiving quercetin achieved plasma quercetin level 23-fold higher than levels in those on placebo. The results showed no quercetin effect on serum total cholesterol, LDL-cholesterol, HDL-cholesterol or triglyceride levels. Nor was there any effect on other factors considered to be indicators of risk for cardiovascular/thrombogenic disease, including platelet aggregation, platelet thromboxane B2 production, blood pressure and resting heart rate. There was no effect on levels of (n-6) or (n-3) polyunsaturated fatty acids in serum or platelet phospholipids ...|/HUMAN EXPOSURE STUDIES/ Intravenous admin of doses greater than 945 mg/sq m has been associated with nephrotoxicity.|/SIGNS AND SYMPTOMS/ Adverse effects reported with oral quercetin include gastrointestinal effects such as nausea, and rare reports of headache and mild tingling of the extremities ... Intravenous admin of quercetin has been associated with nausea, vomiting, diaphoresis, flushing and dyspnea.|/ALTERNATIVE and IN VITRO TESTS/ Quercetin was reported to have 1% of the estrogenic activity of estradiol in HeLa cells transfected with the human estrogen receptor and the pERE-TK-CAT reporter plasmid ...|For more Human Toxicity Excerpts (Complete) data for QUERCETIN (13 total), please visit the HSDB record page.

3,3',4',5,7-pentahydroxyflavone

Supplied as capsules & tablets|Glycosylated forms include rutin and quercetrin|Intravenous soln in ethanol or DMSO ...

4H-1-Benzopyran-4-one, 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-: ACTIVE|Natural antioxidant ... Plant dye|Flavone dye ...(flavus , Latin for yellow) ... has lost commercial value since the advent of synthetic dyes in 1856

HIGH-PRESSURE LIQUID CHROMATOGRAPHY WAS USED TO ANALYZE FLAVONOIDS FROM PROPOLIS.|QUERCETIN WAS DETERMINED BY GAS CHROMATOGRAPHY/FLAME IONIZATION DETECTION. THE SAMPLE WAS DERIVATIZED WITH TRIMETHYLSILYLIMIDAZOLE & CHOLESTEROL WAS USED AS INTERNAL STD. THE CALIBRATION CURVE WAS LINEAR FOR 4-16 MUG, & THE MINIMUM DETECTABLE AMT WAS 6.64X10-10 MOLE WITH 98.5% RECOVERY.|Quercetin has been separated from a crude plant extract by high-performance liquid chromatography ... The reaction of quercetin with vanadyl sulphate has been used as basis for a sensitive spectrophotometric method for estimation of quercetin, with a limit of detection of about 0.3 mg/L ... Gel filtration followed by ultraviolet spectroscopy is reported to offer another selective method for determination of quercetin at a level of 5 mg/L ...

Analyte: quercetin; matrix: blood (whole), urine; procedure: high-performance liquid chromatography with photodiode-array ultraviolet detection at 202.8 nm

Food Additives -> COLOUR; -> JECFA Functional Classes|Polyketides [PK] -> Flavonoids [PK12] -> Flavones and Flavonols [PK1211]

Food Additives -> COLOUR;