Low Doses Of Quercetin Research Articles

Quercetin-Induced Enhancement of Nasal Epithelial Cells' Ability to Produce Clara Cell 10-kD Protein In Vitro and In Vivo.

Background: Quercetin, a polyphenolic flavonoid found in various plants and foods, is known to have antioxidant, antiviral and anticancer effects. Although quercetin is well known to exert anti-inflammatory and anti-allergic effects, the precise mechanisms by which quercetin favorably modifies the clinical status of allergic diseases, such as allergic rhinitis (AR), remain unclear. The present study examined whether quercetin could modulate the production of the endogenous anti-inflammatory molecule, Clara cell 10-kD protein (CC10), in vitro and in vivo. Methods: Human nasal epithelial cells (1 × 105 cells/mL) were stimulated with 20 ng/mL of tumor necrosis factor-alpha (TNF) in the presence of quercetin for 24 h. CC10 levels in culture supernatants were examined by ELISA. Sprague Dawley rats were sensitised with toluene 2,4-diisocyanate (TDI) by intranasal instillation of 10% TDI in ethyl acetate at a volume of 5.0 μL once daily for five days. This sensitisation procedure was repeated after an interval of two days. The rats were treated with different dosages of quercetin once daily for five days starting on the 5th day following the second sensitization. Nasal allergy-like symptoms induced by the bilateral application of 5.0 μL of 10% TDI were assessed by counting sneezing and nasal-rubbing behaviours for 10 min immediately after the TDI nasal challenge. The levels of CC10 in nasal lavage fluids obtained 6 h after TDI nasal challenge were examined using ELISA. Results: The treatment of cells with low doses of quercetin (<2.5 μM) scarcely affected TNF-induced CC10 production from nasal epithelial cells. However, the ability of nasal epithelial cells to produce CC10 after TNF stimulation significantly increased on treatment with quercetin doses (>5.0 μM). The oral administration of quercetin (>25 mg/kg) for five days significantly increased the CC10 content in nasal lavage fluids and attenuated the nasal symptoms induced by the TDI nasal challenge. Conclusions: Quercetin inhibits AR development by increasing the ability of nasal epithelial cells to produce CC10.

Investigation of the role of quercetin as a heat shock protein inhibitor on apoptosis in human breast cancer cells.

High expression of heat shock proteins (Hsp) in breast cancer has been closely associated with tumor cell proliferation and thus a poor clinical outcome. Quercetin, a good Hsp inhibitor as a dietary flavonoid, possesses anticarcinogenic properties. Although there are many studies on the effects of quercetin on Hsp levels in human breast cancer cells, research on elucidation of its molecular mechanism continues. Herein, we aimed to investigate the effect of quercetin on Hsp levels and whether quercetin is a suitable therapeutic for two breast cancer cell lines (MCF-7 and MDA-MB-231) representing breast tumors which differed in hormone receptor, aggressiveness and treatment responses. To examine the response to high and low doses of quercetin, the cells were treated with three doses of quercetin (10, 25 and 100μM) determined by MTT. The effects of quercetin on Hsp levels, apoptosis and DNA damage were examined by western blot analysis, caspase activity assay, comet assay and microscopy in human breast cancer cells. Compared to MDA-MB231 cells, MCF-7 cells were more affected by quercetin treatments. Quercetin effectively suppressed the expression of Hsp27, Hsp70 and Hsp90. While quercetin did not induce DNA damage, it triggered apoptosis at high levels. Although an increase in NF-κB levels is observed in the cells exposed to quercetin, the net result is the anticancer effect in case of Hsp depletion and apoptosis induction. Taken together our findings suggested that quercetin can be an effective therapeutic agent for breast cancer therapy regardless of the presence or absence of hormone receptors.

Effects of Low Doses of Quercetin and Genistein on Oxidation and Carbonylation in Hemoglobin and Myoglobin

ABSTRACTProtein-bound carbonyls have been shown to increase with age as well as in numerous diseases including rheumatoid arthritis, adult respiratory syndrome pulmonary fibrosis, diabetes, Parkinson's disease, and Alzheimer's just to mention a few. The effects of the flavonoids quercetin and genistein were investigated according to their ability to inhibit the oxidation of hemoglobin and myoglobin via the Fenton's pathway. Antioxidative activity of the flavonoids were determined by oxidizing hemoglobin and myoglobin in separate experiments with 50 μM Fe2+ and 0.01 mM hydrogen peroxide (H2O2) with and without quercetin and/or genistein. The samples were treated singly with either quercetin, genistein, or in combination at concentrations of 1.0, 1.5, 2.0, 2.5, 3.0, and 3.5 μM, respectively, dissolved in dimethyl sulfoxide (DMSO). Samples were then incubated in a water bath at 37°C for 8, 12, and 24 hr, respectively. Levels of carbonylation were assayed by the protein carbonyl assay and the carbonyl levels quantified and expressed per mg of protein. The results indicate that protein carbonyls for samples treated with quercetin or genistein decreased in a dose-dependent manner compared to the controls. That of quercetin compared to genistein was more efficient in reducing the levels of protein carbonylation in hemoglobin and myoglobin, respectively. The combination of both flavonoids did show a gradual decrease in carbonyl compounds for only hemoglobin for all the doses and times tested. The results indicate that both flavonoids at low doses inhibited carbonylation in both hemoglobin and myoglobin and the inhibition may be attributed to the prevention of protein oxidation.

Abstract C60: Exposure of low doses of quercetin on DNA oxidation in Pectobacterium carotovorum KD 100 and Agrobacterium tumefaciens GV 3103.

Abstract Oxidative stress may be a key factor in the onset of certain diseases, including cancer. Oxy-radicals play important roles in the initiation, promotion, and progression of carcinogenesis. During the course of DNA excision and repair of oxidized, deaminated or alkylated bases apurinic/apyrimidinic (AP) or abasic sites are formed. The flavonoid quercetin was investigated for its ability to inhibit the oxidation of plasmid from Pectobacterium carotovorum KD 100 and Agrobacterium tumefaciens GV 3103 using the Fenton's chemistry. Utilizing a Colorimetric Assay Kit (Oxford Biomedical Research #FR09, Oxford, MI) for DNA damage quantification, AP sites were measured for plasmid following incubation with low doses of quercetin (1, 2, 2.5, 3, 3.5 µM) or without for 12 or 24 hr. With the increasing concentrations of quercetin the number of AP sites in each sample significantly decreased more for Pectobacterium carotovorum KD 100 compared to Agrobacterium tumefaciens GV 3103 in a time- and dose-dependent manner in comparison to their respective controls for the 12 and 24 hr incubation periods. The differences in decrease in AP sites can be linked to structural differences between the two bacterial strains and/or decreased oxidation for each sample with increased quercetin aliquots. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):C60. Citation Format: William Y. Boadi, Damitea Johnson, Korsi Dumenyo. Exposure of low doses of quercetin on DNA oxidation in Pectobacterium carotovorum KD 100 and Agrobacterium tumefaciens GV 3103. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr C60.

Stimulus-specific regulation of CD63 and CD203c membrane expression in human basophils by the flavonoid quercetin

Background Flavonoids, such as quercetin, were reported to inhibit histamine release and cytokine production by basophils, but there is no evidence describing their action on membrane markers and intracellular biochemical pathways. Objective The aim of the study was to examine the effect of several quercetin doses on an in vitro human basophil activation system that evaluates up-regulation of membrane markers in response to agonists. Methods Leukocyte buffy coats from K 2-EDTA anti-coagulated blood were treated with different concentrations of quercetin and triggered with anti-IgE (“allergy model”) and with N-formyl-Met-Leu-Phe (fMLP) (“inflammation model”). Basophils were captured as CD123 bright/HLA-DR non-expressing cells in a flow cytometry analysis and fluorescence values of CD63-FITC, CD203c-PE and CD123-PECy5 were used to produce dose response curves. Results Quercetin at a dose of 10 μg/ml strongly inhibited CD63 and CD203c membrane up-regulation triggered by both agonists, but it neither affected cell viability nor changed the expression of the phenotypic marker CD123. The anti-IgE model appeared highly sensitive to the effect of quercetin: a dose as low as 0.01 μg/ml was able to significantly decrease CD63 and CD203c membrane expression. In the fMLP model the dose response was different: quercetin doses from 0.01 to 0.1 μg/ml significantly increased up-regulation of membrane markers, achieving the highest effect with CD63. Conclusion Very low doses of quercetin, within the pharmacological range, inhibit IgE-mediated membrane marker's up-regulation but prime the response to the chemotactic peptide fMLP; this stimulus specificity may have implications on the possible therapeutic action of the flavonoid in different pathologies.

Participation of α 2 Receptors in the Antinociceptive Activity of Quercetin

The present work was planned to evaluate the antinociceptive activity of quercetin, its site of action, and the involvement of adrenergic receptors in mediating the antinociceptive activity in thermal and chemonociceptive assays. Eight groups were employed in this study: Groups I, II, and III received quercetin alone in different doses, group IV animals were administered clonidine, group V animals were co-administered quercetin and clonidine, group VI animals were administered yohimbine 30 minutes prior to administratin of quercetin, group VII animals were administered yohimbine 30 minutes prior to co-administration of quercetin and clonidine, and group VIII animals were administered 0.5% carboxymethylcellulose in saline (vehicle for quercetin). The thermal nociception was measured by tail flick and hot plate methods. Quercetin produced a significant analgesic effect in a dose-dependent manner. Co-administration of low doses of quercetin and clonidine produced a synergistic analgesic effect. Pretreatment with yohimbine significantly reversed quercetin-as well as clonidine/quercetin combination-induced effects. The results of this study reveal that quercetin induces an antinociceptive effect and that this effect involves primarily the modulation of adrenergic pathways.

Polyphenols from Alcoholic Apple Cider Are Absorbed, Metabolized and Excreted by Humans

We determined the uptake and excretion of low doses of polyphenols in six subjects who each consumed 1.1 L of an alcoholic cider beverage. Over a 24-h period, no phloretin was detected in plasma (detection limit = 0.036 micromol/L), but 21 +/- 5% of the dose (4.8 mg) was excreted in the urine. In contrast, from a low dose of 1.6-mg quercetin equivalents, no quercetin was found in urine or plasma, but 3'-methyl quercetin was detected in plasma [C(max) (maximum concentration) = 0.14 +/- 0.19 micromol/L; range: 0 to 0.44 micromol/L]. No flavanol monomers (dose of free (+)-catechin and (-)-epicatechin = 3.5 mg) were detected in urine or plasma (detection limit: 0.01 micromol/L). Caffeic acid (total dose including esters = 11 mg) was detected only in plasma within 2 h, with C(max) = 0.43 +/- 0.3 micromol/L (range: 0.18 to 0.84 micromol/L). An almost 3-fold increase in hippuric acid was detected in 24-h urine (74 +/- 29 micromol/L; range: 38-116 micromol/L), compared with a prestudy value of 19 +/- 9 micromol/L. These data show that polyphenols are taken up from cider, that phloretin is excreted in the urine and suggest that low doses of quercetin are extensively methylated in humans.

Changes in the content of sugars and amino acid in the fruit of Lycopersicon esculentum after quercetin treatment

We studied the effect of low doses of quercetin, an exogenous flavonoid, on the content of various sugars in the fruit of Lycopersicon esculentum. The content of glucose in tomatoes calculated per dry weight increased 1.5- to 4.5-fold in the experiment compared with the control. Simultaneously, we observed a decrease in the content of total amino acids in the fruit of quercetin-treated plants (1.5 times compared to the control). The most significant changes were noted in the content of amino acids: glutamic (1.7-fold) and aspartic (1.6-fold). The treatment of plants with quercetin did not decrease their productivity. An increase in the level of glucose in tomatoes has been found in all 12 varieties studied. We discuss the mechanism of the possible effect of quercetin on tomato plants.

Induction of an adaptive response to quercetin, mitomycin C and hydrogen peroxide by low doses of quercetin in V79 Chinese hamster cells

The adaptive response is a phenomenon by which cells exposed to low, non-cytotoxic doses of a genotoxicant become significantly resistant to a subsequent higher dose of the same or another genotoxic agent. Induction of the adaptive response has been mainly studied using ionizing radiation and alkylating agents as genotoxic agents. However, other mutagenic agents may warrant further study, since the adaptive response as a whole may be an important general biological mechanism to maintain genetic integrity and thus could prevent carcinogenic initiation of cells. The exposure to mutagenic agents present, or formed, in the diet is considered an important factor in the etiology of human tumors and a considerable number of these agents have not yet been identified or characterized. Flavonoids are a large group of polyphenolic quinoids found in a wide variety of edible fruits and vegetables and a few, such as quercetin, present genotoxic activity in vitro. The mechanisms of mutagenicity of quercetin involve the production of oxygen radicals through an autoxidation process dependent on pH value and the presence of oxygen. Although there are few doubts regarding the mutagenicity of quercetin in vitro, carcinogenicity of flavonoid is still controversial. In view of these conflicting results and the radiomimetic nature of the mutagenicity of flavonoids, we addressed the question of cell exposure to quercetin at the low levels present in the diet leading to adaptation to further exposure to mutagens or carcinogens. The work reported here concerns induction of an adaptive response by low doses of quercetin to challenging doses of quercetin and other compounds, namely hydrogen peroxide and mitomycin C, using induction of chromosomal aberrations in V79 cells as the end point.