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Sample records for quercetin transiently increases

  1. Quercetin transiently increases energy expenditure but persistently decreases circulating markers of inflammation in C57BL/6J mice fed a high-fat diet.

    PubMed

    Stewart, Laura K; Soileau, Jeff L; Ribnicky, David; Wang, Zhong Q; Raskin, Ilya; Poulev, Alexander; Majewski, Martin; Cefalu, William T; Gettys, Thomas W

    2008-07-01

    Quercetin, a polyphenolic compound and a major bioflavonoid in the human diet, has anti-inflammatory properties and has been postulated to enhance energy expenditure (EE). We sought to determine whether quercetin alters body weight, body composition, EE, and circulating markers of inflammation. At 6 weeks (W) of age, 2 cohorts of C57BL/6J mice (N = 80) were placed on one of 2 diets for 3W or 8W: (1) high fat (HF) (45% kcal fat) or (2) high fat + quercetin (HF + Q) (45% kcal fat + 0.8% quercetin). Quercetin concentrations in the diet and plasma were evaluated using mass spectrometry. Body weight, composition (nuclear magnetic resonance), and food consumption were measured weekly. Energy expenditure was measured by indirect calorimetry at 3 and 8W, and inflammatory markers were measured in plasma obtained at 8W. The presence of quercetin in the HF diet did not alter food consumption over time in the HF + Q group and did not differ from the HF group at any time point. However, circulating plasma quercetin concentrations declined between 3 and 8W. At 3W, EE was higher during both day and night phases (P < .0001) in the HF + Q group compared with the HF group; but this difference was not detected at 8W and did not translate into significant differences between the HF + Q and HF groups with respect to body weight or body composition. During the night phase, concentrations of the inflammatory markers (interferon-gamma, interleukin-1alpha, and interleukin-4) were significantly lower when compared with HF treatment group (P < .05). Dietary supplementation with quercetin produces transient (3W) increases in EE that are not detected after 8W on the diet. A corresponding decrease in circulating quercetin between 3 and 8W suggests that metabolic adaptation may have diminished the impact of quercetin's early effect on EE and diminished its overall effect on nutrient partitioning and adiposity. However, quercetin at the levels provided was effective in reducing circulating

  2. Rat Pial Microvascular Responses to Transient Bilateral Common Carotid Artery Occlusion and Reperfusion: Quercetin's Mechanism of Action.

    PubMed

    Lapi, D; Vagnani, S; Pignataro, G; Esposito, E; Paterni, M; Colantuoni, A

    2012-01-01

    The aim of the present study was to assess quercetin's mechanism of action in rat pial microvessels during transient bilateral common carotid artery occlusion (BCCAO) and reperfusion. Rat pial microcirculation was visualized using fluorescence microscopy through a closed cranial window. Pial arterioles were classified in five orders of branchings. In ischemic rats, 30 min BCCAO and 60 min reperfusion caused arteriolar diameter decrease, microvascular leakage, leukocyte adhesion in venules, and reduction of capillary perfusion. Quercetin highest dose determined dilation in all arteriolar orders, by 40 ± 4% of baseline in order 2 vessels, and prevented microvascular permeability [0.15 ± 0.02 normalized gray levels (NGL)], leukocyte adhesion, and capillary failure. Protein kinase C (PKC) inhibition exerted by chelerythrine prior to quercetin attenuated quercetin-induced effects: order 2 arterioles dilated by 19.0 ± 2.4% baseline, while there was an increase in permeability (0.40 ± 0.05 NGL) and leukocyte adhesion with a marked decrease in capillary perfusion. Tyrosine kinase (TK) inhibition by tyrphostin 47 prior to quercetin lessened smaller pial arterioles responses, dilating by 20.7 ± 2.5% of baseline, while leakage increased (0.39 ± 0.04 NGL) sustained by slight leukocyte adhesion and ameliorated capillary perfusion. Inhibition of endothelium nitric oxide synthase (eNOS) by N(G)-nitro-L-arginine-methyl ester (L-NAME) prior to PKC or TK reduced the quercetin's effects on pial arteriolar diameter and leakage. eNOS inhibition by L-NAME reduced quercetin effects on pial arteriolar diameter and leakage. Finally, combined inhibition of PKC and TK prior to quercetin abolished quercetin-induced effects, decreasing eNOS expression, while blocking ATP-sensitive potassium (K(ATP)) channels by glibenclamide suppressed arteriolar dilation. In conclusion, the protective effects of quercetin could be due to different mechanisms resulting in NO

  3. Quercetin Increases Hepatic Homocysteine Remethylation and Transsulfuration in Rats Fed a Methionine-Enriched Diet.

    PubMed

    Meng, Bin; Gao, Weina; Wei, Jingyu; Pu, Lingling; Tang, Zhenchuang; Guo, Changjiang

    2015-01-01

    This study was aimed at investigating the effects of quercetin on mRNA expression and activity of critical enzymes in homocysteine metabolism in rats fed a methionine-enriched diet. Rats were fed for 6 weeks the following diets, that is, control, 0.5% quercetin, 1.0% methionine, and 1.0% methionine plus 0.5% quercetin diets. Serum homocysteine was significantly increased after methionine treatment and decreased after the addition of quercetin. The mRNA expression of methionine synthase was significantly increased after methionine or methionine plus quercetin supplementation, while its enzymatic activity was significantly increased after methionine plus quercetin supplementation. The mRNA expression and enzymatic activity of cystathionine β-synthase and cystathionine γ-lyase were upregulated after quercetin, methionine, or quercetin plus methionine treatment and a more significant increase was observed for hepatic cystathionine β-synthase in the methionine plus quercetin treated rats, suggesting an interaction between methionine and quercetin. Meanwhile, hepatic ratio of S-adenosylmethionine to S-adenosylhomocysteine was significantly decreased in response to methionine supplementation and normalized after the addition of quercetin. It is concluded that quercetin reduces serum homocysteine by increasing remethylation and transsulfuration of homocysteine in rats exposed to a methionine-enriched diet.

  4. Enriched cereal bars are more effective in increasing plasma quercetin compared with quercetin from powder-filled hard capsules.

    PubMed

    Egert, Sarah; Wolffram, Siegfried; Schulze, Beate; Langguth, Peter; Hubbermann, Eva Maria; Schwarz, Karin; Adolphi, Berit; Bosy-Westphal, Anja; Rimbach, Gerald; Müller, Manfred James

    2012-02-01

    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. PMID:21774840

  5. Quercetin reduced inflammation and increased antioxidant defense in rat adjuvant arthritis.

    PubMed

    Gardi, C; Bauerova, K; Stringa, B; Kuncirova, V; Slovak, L; Ponist, S; Drafi, F; Bezakova, L; Tedesco, I; Acquaviva, A; Bilotto, S; Russo, G L

    2015-10-01

    Novel therapies for rheumatoid arthritis also include the use of naturally occurring compounds possessing antioxidant properties. In the present work, the effects of oral administration of quercetin were investigated in a rat model of adjuvant arthritis. Arthritis was induced by a single intradermal injection of heat-inactivated Mycobacterium butyricum in incomplete Freund's adjuvant. The experimental groups were treated with an oral daily dose of 150 mg/kg b.w. of quercetin for 28 days. Results indicated that quercetin was able to ameliorate all markers of inflammation and oxidative stress measured. Quercetin lowered levels of interleukin-1β, C-reactive protein, and monocyte chemotactic protein-1 and restored plasma antioxidant capacity. In addition, quercetin inhibited the enzymatic activity of pro-inflammatory 12/15-lipoxygenase in lung and liver and increased the expression of heme oxygenase-1 in joint and lung of arthritic rats. Finally, quercetin inhibited the 2-fold increase of NF-қB activity observed in lung, liver and joint after induction of arthritis. PMID:26297952

  6. Quercetin increases macrophage cholesterol efflux to inhibit foam cell formation through activating PPARγ-ABCA1 pathway

    PubMed Central

    Sun, Liqiang; Li, En; Wang, Feng; Wang, Tao; Qin, Zhiping; Niu, Shaohui; Qiu, Chunguang

    2015-01-01

    The accumulation of cholesterol in macrophages could induce the formation of foam cells and increase the risk of developing atherosclerosis. We wonder if quercetin, one of flavonoids with anti-inflammation functions in different cell types, could elevate the development of foam cells formation in atherosclerosis. We treated foam cells derived from oxLDL induced THP-1 cells with quercetin, and evaluated the foam cells formation, cholesterol content and apoptosis of the cells. We found that quercetin induced the expression of ABCA1 in differentiated THP-1 cells, and increased the cholesterol efflux from THP-1 cell derived foam cells. Eventually, cholesterol level and the formation of foam cell derived from THP-1 cells decreased after quercetin treatment. In addition, quercetin activated PPARγ-LXRα pathway to upregulate ABCA1 expression through increasing protein level of PPARγ and its transcriptional activity. Inhibition of PPARγ activity by siRNA knockdown or the addition of chemical inhibitor, GW9662, abolished quercetin induced ABCA1 expression and cholesterol efflux in THP-1 derived macrophages. Our data demonstrated that quercetin increased cholesterol efflux from macrophages through upregulating the expressions of PPARγ and ABCA1. Taken together, increasing uptake of quercetin or quercetin-rich foods would be an effective way to lower the risk of atherosclerosis. PMID:26617799

  7. Fermentation enhances the in vitro antioxidative effect of onion (Allium cepa) via an increase in quercetin content.

    PubMed

    Yang, Eun-Ju; Kim, Sang-In; Park, Sang-Yun; Bang, Han-Yeol; Jeong, Ji Hye; So, Jai-Hyun; Rhee, In-Koo; Song, Kyung-Sik

    2012-06-01

    Yellow onion (Allium cepa) extract showed enhanced antioxidative effects in 2,2-diphenyl-1-picrylhydrazyl (DPPH), Trolox equivalent antioxidant capacity (TEAC) and 5-(and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate and acetyl ester (CM-H(2)DCFDA) assay after being treated with a crude enzyme extract from soybean paste fungi, Aspergillus kawachii. HPLC analysis showed two increased and two decreased peaks after enzyme treatment. The decreased peaks were identified as quercetin-3,4'-di-O-β-d-glucoside (1) and quercetin-4'-O-β-d-glucoside (2), and peaks that increased were quercetin-3-O-β-d-glucoside (3) and quercetin (4), respectively. It was expected that 3 and 4 were originated from the glucosidic cleavage of their glucosides, 1 and 2. Among the increased compounds, only quercetin (4) showed strong antioxidative activity in the DPPH assay. In addition, the protective effect against glutamate-induced neurotoxicity in HT22 cells was increased when treated with 25 μg/ml of fermented onion. The enhanced neuroprotective effect was also originated from the increased quercetin content. As a consequence, fermentation raised the quercetin content in onion, and subsequently increased the antioxidative and neuroprotective activities.

  8. The quercetin paradox

    SciTech Connect

    Boots, Agnes W. . E-mail: a.boots@farmaco.unimaas.nl; Li, Hui; Schins, Roel P.F.; Duffin, Rodger; Heemskerk, Johan W.M.; Bast, Aalt; Haenen, Guido R.M.M.

    2007-07-01

    Free radical scavenging antioxidants, such as quercetin, are chemically converted into oxidation products when they protect against free radicals. The main oxidation product of quercetin, however, displays a high reactivity towards thiols, which can lead to the loss of protein function. The quercetin paradox is that in the process of offering protection, quercetin is converted into a potential toxic product. In the present study, this paradox is evaluated using rat lung epithelial (RLE) cells. It was found that quercetin efficiently protects against H{sub 2}O{sub 2}-induced DNA damage in RLE cells, but this damage is swapped for a reduction in GSH level, an increase in LDH leakage as well as an increase of the cytosolic free calcium concentration. To our knowledge, this is the first study that indicates that the quercetin paradox, i.e. the exchange of damage caused by quercetin and its metabolites, also occurs in living lung cells. Following depletion of GSH in the cells by BSO pre-treatment, this quercetin paradox becomes more pronounced, confirming that the formation of thiol reactive quercetin metabolites is involved in the quercetin paradox. The quercetin paradox in living cells implies that the anti-oxidant directs oxidative damage selectively to thiol arylation. Apparently, the potential toxicity of metabolites formed during the actual antioxidant activity of free radical scavengers should be considered in antioxidant supplementation.

  9. Esterification of Quercetin Increases Its Transport Across Human Caco-2 Cells.

    PubMed

    Hu, Jiang-Ning; Zou, Xian-Guo; He, Yi; Chen, Fang; Deng, Ze-Yuan

    2016-07-01

    Plant polyphenols showed useful biochemical characteristics in vitro; however, the assessments of their clinical applications in vivo are restricted by their limited bioavailability due to their strong resistance to 1st-pass effects during absorption. In order to improve the bioavailability of quercetin (QU), the ester derivative of QU (3,3',4',5,7-pentahydroxy flavones, TAQU) was synthesized, followed by examining the oil-water partition coefficient as well as the transport mechanisms of QU and its ester derivative (TAQU) using human Caco-2 cells. The transport characteristics of QU and TAQU transport under different conditions (different concentrations, time, pH, temperature, tight junctions, and potential transporters) were systematically investigated. Results showed that QU had a lower permeability coefficient (2.82 × 10(-6) cm/s) for apical-to-basolateral (AP-BL) transport over 5 to 50 μM, whereas the transport rate for AP to BL flux of TAQU (5.23 × 10(-6) cm/s) was significantly greater than that of QU. Paracellular pathways were not involved during the transport of both QU and TAQU. QU was poorly absorbed by active transport, whereas TAQU was mostly absorbed by passive diffusion. Efflux transporters, P-glycoproteins, multidrug resistance proteins were proven to participate in the transport process of QU, but not in that of TAQU. These results suggested that improving the lipophicity of QU by esterification could increase the transport of QU across Caco-2 cells. PMID:27301074

  10. Age-related increases in F344 rat intestine microsomal quercetin glucuronidation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this study was to establish the extent age modifies intestinal quercetin glucuronidation capacity. Pooled microsomal fractions of three equidistant small intestine (SI) segments from 4, 12, 18, and 28 mo male F344 rats (n=8/group) were employed to model the enzyme kinetics of UDP-gl...

  11. Radiofrequency ablation combined with liposomal quercetin to increase tumour destruction by modulation of heat shock protein production in a small animal model

    PubMed Central

    Yang, Wei; Ahmed, Muneeb; Tasawwar, Beenish; Levchenko, Tatyana; Sawant, Rupa R.; Collins, Michael; Signoretti, Sabina; Torchilin, Vladimir; Goldberg, S. Nahum

    2012-01-01

    Purpose To investigate the effect of heat shock protein (HSP) modulation on tumour coagulation by combining radiofrequency (RF) ablation with adjuvant liposomal quercetin and/or doxorubicin in a rat tumour model. Methods Sixty R3230 breast adenocarcinoma tumours/animals were used in this IACUC-approved study. Initially, 60 tumours (n = 6, each subgroup) were randomised into five groups: (1) RF alone, (2) intravenous (IV) liposomal quercetin alone (1 mg/kg), (3) IV liposomal quercetin followed 24 h later with RF, (4) RF followed 15 min later by IV liposomal doxorubicin (8 mg/kg), (5) IV liposomal quercetin 24 h before RF followed by IV liposomal doxorubicin 15 min post-ablation. Animals were sacrificed 4 or 24 h post-treatment and gross coagulation diameters were compared. Next, immunohistochemistry staining was performed for Hsp70 and cleaved caspase-3 expression. Comparisons were performed by using Student t-tests or ANOVA. Results Combination RF-quercetin significantly increased coagulation size compared with either RF or liposomal quercetin alone (13.1 ± 0.7 mm vs. 8.8 ± 1.2 mm or 2.3 ± 1.3 mm, respectively, P < 0.001 for all comparisons). Triple therapy (quercetin-RF-doxorubicin) showed larger coagulation diameter (14.5 ± 1.0mm) at 24 h than quercetin-RF (P = 0.016) or RF-doxorubicin (13.2 ± 1.3 mm, P = 0.042). Combination quercetin-RF decreased Hsp70 expression compared with RF alone at both 4 h (percentage of stained cells/hpf 22.4 ± 13.9% vs. 38.8 ± 16.1%, P < 0.03) and 24 h (45.2 ± 10.5% vs. 81.1 ± 3.6%, P < 0.001). Quercetin-RF increased cleaved caspase-3 expression at both 4 h (percentage of stained cells/hpf 50.7 ± 13.4% vs. 41.9 ± 15.1%, P < 0.03) and 24 h (37.4 ± 7.8% vs. 33.2 ± 6.5%, P = 0.045); with, triple therapy (quercetin-RF-doxorubicin) resulting in the highest levels of apoptosis (45.1 ± 10.7%) at 24 h. Similar trends were observed for rim thickness. Conclusions Suppression of HSP production using adjuvant liposomal quercetin can

  12. Quercetin-induced Growth Inhibition in Human Bladder Cancer Cells Is Associated with an Increase in Ca-activated K Channels.

    PubMed

    Kim, Yangmi; Kim, Wun-Jae; Cha, Eun-Jong

    2011-10-01

    Quercetin (3,3',4',5,7-pentahydroxyflavone) is an attractive therapeutic flavonoid for cancer treatment because of its beneficial properties including apoptotic, antioxidant, and antiproliferative effects on cancer cells. However, the exact mechanism of action of quercetin on ion channel modulation is poorly understood in bladder cancer 253J cells. In this study, we demonstrated that large conductance Ca(2+)-activated K(+) (BK(Ca)) or MaxiK channels were functionally expressed in 253J cells, and quercetin increased BK(Ca) current in a concentration dependent and reversible manner using a whole cell patch configuration. The half maximal activation concentration (IC(50)) of quercetin was 45.5±7.2 µM. The quercetin-evoked BK(Ca) current was inhibited by tetraethylammonium (TEA; 5 mM) a non-specific BK(Ca) blocker and iberiotoxin (IBX; 100 nM) a BK(Ca)-specific blocker. Quercetin-induced membrane hyperpolarization was measured by fluorescence-activated cell sorting (FACS) with voltage sensitive dye, bis (1,3-dibutylbarbituric acid) trimethine oxonol (DiBAC(4)(3); 100 nM). Quercetin-evoked hyperpolarization was prevented by TEA. Quercetin produced an antiproliferative effect (30.3±13.5%) which was recovered to 53.3±10.5% and 72.9±3.7% by TEA and IBX, respectively. Taken together our results indicate that activation of BK(Ca) channels may be considered an important target related to the action of quercetin on human bladder cancer cells.

  13. Concentrations of foliar quercetin in natural populations of white birch (Betula pubescens) increase with latitude.

    PubMed

    Stark, Sari; Julkunen-Tiitto, Riitta; Holappa, Esa; Mikkola, Kari; Nikula, Ari

    2008-11-01

    We investigated latitudinal and regional variations in the composition and concentrations of foliar flavonoids and condensed tannins in wild populations of white birch (Betula pubescens EHRH) in a large climatic transect in Finland. Concentrations of quercetin derivatives were correlated positively with latitude. By contrast, the concentrations of apigenin and naringenin derivatives were correlated negatively with latitude. These compound-specific latitudinal gradients compensated each other, resulting in no changes in the concentration of total flavonoids. Our results thus demonstrate a qualitative, but not quantitative, latitude-associated gradient in the foliar flavonoids in white birch. Due to higher antioxidant capacity of the quercetin derivatives in relation to other flavonoids, the qualitative change can reflect higher adaptation to light in the north than south. An investigation on a regional scale in the northern boreal zone showed that the temperature sum was correlated positively and soil P concentration was correlated negatively with the concentrations of foliar flavonoid, while the concentration of condensed tannins was correlated with slope. The variation in concentrations of flavonoids at large-scale geographical patterns is in line with the conjecture that foliar flavonoids are synthesized for protection against photooxidative stress.

  14. Suppression of HSP27 increases the anti-tumor effects of quercetin in human leukemia U937 cells

    PubMed Central

    CHEN, XI; DONG, XIU-SHUAI; GAO, HAI-YAN; JIANG, YONG-FANG; JIN, YING-LAN; CHANG, YU-YING; CHEN, LI-YAN; WANG, JING-HUA

    2016-01-01

    Quercetin, a natural flavonoid, inhibits the growth of leukemia cells and induces apoptosis. Heat shock protein 27 (HSP27) has been reported to promote the development of leukemia by protecting tumor cells from apoptosis through various mechanisms. The present study investigated the effects of small hairpin (sh)RNA-mediated HSP27 knockdown on the anti-cancer effects of quercetin in U937 human leukemia cells. Cells were transfected with recombinant lentiviral vector pCMV-G-NR-U6-shHSP27 (shHSP27), which expressed shRNA specifically targeting the HSP27 gene, alone or in combination with quercetin. The results showed that shHSP27 and quercetin synergistically inhibited U937 cell proliferation and induced apoptosis by decreasing the Bcl2-to-Bax ratio. Furthermore, this combined treatment significantly suppressed the infiltration of tumor cells and the expression of angiogenesis-associated proteins HIF1α and VEGF. Compared with shHSP27 or quercetin alone, shHSP27 plus quercetin markedly decreased the protein expression of cyclinD1 and thus blocked the cell cycle at G1 phase. The Notch/AKT/mTOR signaling pathway is important in tumor aggressiveness; quercetin plus shHSP27 significantly decreased Notch 1 expression and the phosphorylation levels of the downstream signaling proteins AKT and mTOR. The inhibitory effects of quercetin plus shHSP27 on this pathway may thus have been responsible for the cell cycle arrest, inhibition of proliferations and infiltration as well as enhancement of apoptosis. Therefore, these findings collectively suggested that suppression of HSP27 expression amplified the anti-cancer effects of quercetin in U937 human leukemia cells, and that quercetin in combination with shHSP27 represents a promising therapeutic strategy for human leukemia. PMID:26648539

  15. Differential Effects of Quercetin and Quercetin Glycosides on Human α7 Nicotinic Acetylcholine Receptor-Mediated Ion Currents

    PubMed Central

    Lee, Byung-Hwan; Choi, Sun-Hye; Kim, Hyeon-Joong; Jung, Seok-Won; Hwang, Sung-Hee; Pyo, Mi-Kyung; Rhim, Hyewhon; Kim, Hyoung-Chun; Kim, Ho-Kyoung; Lee, Sang-Mok; Nah, Seung-Yeol

    2016-01-01

    Quercetin is a flavonoid usually found in fruits and vegetables. Aside from its antioxidative effects, quercetin, like other flavonoids, has a various neuropharmacological actions. Quercetin-3-O-rhamnoside (Rham1), quercetin-3-O-rutinoside (Rutin), and quercetin-3-(2(G)-rhamnosylrutinoside (Rham2) are mono-, di-, and tri-glycosylated forms of quercetin, respectively. In a previous study, we showed that quercetin can enhance α7 nicotinic acetylcholine receptor (α7 nAChR)-mediated ion currents. However, the role of the carbohydrates attached to quercetin in the regulation of α7 nAChR channel activity has not been determined. In the present study, we investigated the effects of quercetin glycosides on the acetylcholine induced peak inward current (IACh) in Xenopus oocytes expressing the α7 nAChR. IACh was measured with a two-electrode voltage clamp technique. In oocytes injected with α7 nAChR copy RNA, quercetin enhanced IACh, whereas quercetin glycosides inhibited IACh. Quercetin glycosides mediated an inhibition of IACh, which increased when they were pre-applied and the inhibitory effects were concentration dependent. The order of IACh inhibition by quercetin glycosides was Rutin≥Rham1>Rham2. Quercetin glycosides-mediated IACh enhancement was not affected by ACh concentration and appeared voltage-independent. Furthermore, quercetin-mediated IACh inhibition can be attenuated when quercetin is co-applied with Rham1 and Rutin, indicating that quercetin glycosides could interfere with quercetin-mediated α7 nAChR regulation and that the number of carbohydrates in the quercetin glycoside plays a key role in the interruption of quercetin action. These results show that quercetin and quercetin glycosides regulate the α7 nAChR in a differential manner. PMID:27098860

  16. The cranberry flavonoids PAC DP-9 and quercetin aglycone induce cytotoxicity and cell cycle arrest and increase cisplatin sensitivity in ovarian cancer cells.

    PubMed

    Wang, Yifei; Han, Alex; Chen, Eva; Singh, Rakesh K; Chichester, Clinton O; Moore, Richard G; Singh, Ajay P; Vorsa, Nicholi

    2015-05-01

    Cranberry flavonoids (flavonols and flavan-3-ols), in addition to their antioxidant properties, have been shown to possess potential in vitro activity against several cancers. However, the difficulty of isolating cranberry compounds has largely limited anticancer research to crude fractions without well-defined compound composition. In this study, individual cranberry flavonoids were isolated to the highest purity achieved so far using gravity and high performance column chromatography and LC-MS characterization. MTS assay indicated differential cell viability reduction of SKOV-3 and OVCAR-8 ovarian cancer cells treated with individual cranberry flavonoids. Treatment with quercetin aglycone and PAC DP-9, which exhibited the strongest activity, induced apoptosis, led to caspase-3 activation and PARP deactivation, and increased sensitivity to cisplatin. Furthermore, immunofluorescence microscopy and western blot study revealed reduced expression and activation of epidermal growth factor receptor (EGFR) in PAC DP-9 treated SKOV-3 cells. In addition, quercetin aglycone and PAC DP-9 deactivated MAPK-ERK pathway, induced downregulation of cyclin D1, DNA-PK, phospho-histone H3 and upregulation of p21, and arrested cell cycle progression. Overall, this study demonstrates promising in vitro cytotoxic and anti-proliferative properties of two newly characterized cranberry flavonoids, quercetin aglycone and PAC DP-9, against ovarian cancer cells. PMID:25776829

  17. Effect of different exposed lights on quercetin and quercetin glucoside content in onion (Allium cepa L.).

    PubMed

    Ko, Eun Young; Nile, Shivraj Hariram; Sharma, Kavita; Li, Guan Hao; Park, Se Won

    2015-07-01

    Quercetin and quercetin glucosides are the major flavonols present in onion (Allium cepa L.) and are predominantly present as quercetin, quercetin-3,4'-diglucoside and quercetin-4'-glucoside. Effect of different light wavelengths on onion after harvest and storage, with fluorescent, blue, red and ultra violet light influenced the quercetin and quercetin glucosides profile. In a peeled onion, all the light treatments elevated quercetin content in bulb. Among them, particularly fluorescent light effect was more eminent which stimulates the maximum synthesis of quercetin in onion. In case of whole onion bulb, skin and pulp showed different responses to light treatment, respectively. The pulp had the highest quercetin glucosides under blue light, whereas the lowest under fluorescent light. Onion skin showed nearly opposite pattern as compared to the pulp. In particular, light treatment proved to be a better way to increase the level of quercetin content in onions which might be utilized for industrial production of bioactive compounds from onion and onion waste products.

  18. Transient Increased Exudation after Photodynamic Therapy of Intraocular Tumors

    PubMed Central

    Mashayekhi, Arman; Shields, Carol L.; Shields, Jerry A.

    2013-01-01

    To report transient increased exudation after photodynamic therapy (PDT) of three different intraocular tumors (retinal hemangioblastoma, retinal astrocytoma, amelanotic choroidal melanoma). PDT with verteporfin (6 mg/m2 body surface area) was delivered at a dose of 50 J/cm2 and intensity of 600 mW/cm2 over 83 s. All patients experienced decreased vision within a few days following PDT. Optical coherence tomography showed development of subfoveal fluid in all cases and noncystoid intraretinal edema in the eye with juxtapapillary retinal hemangioblastoma. There was complete absorption of retinal/subretinal fluid with improvement of visual acuity to 20/20 in all cases between 3 weeks to 4 months after PDT. PMID:23580859

  19. Quercetin, Inflammation and Immunity

    PubMed Central

    Li, Yao; Yao, Jiaying; Han, Chunyan; Yang, Jiaxin; Chaudhry, Maria Tabassum; Wang, Shengnan; Liu, Hongnan; Yin, Yulong

    2016-01-01

    In vitro and some animal models have shown that quercetin, a polyphenol derived from plants, has a wide range of biological actions including anti-carcinogenic, anti-inflammatory and antiviral activities; as well as attenuating lipid peroxidation, platelet aggregation and capillary permeability. This review focuses on the physicochemical properties, dietary sources, absorption, bioavailability and metabolism of quercetin, especially main effects of quercetin on inflammation and immune function. According to the results obtained both in vitro and in vivo, good perspectives have been opened for quercetin. Nevertheless, further studies are needed to better characterize the mechanisms of action underlying the beneficial effects of quercetin on inflammation and immunity. PMID:26999194

  20. Quercetin, Inflammation and Immunity.

    PubMed

    Li, Yao; Yao, Jiaying; Han, Chunyan; Yang, Jiaxin; Chaudhry, Maria Tabassum; Wang, Shengnan; Liu, Hongnan; Yin, Yulong

    2016-03-01

    In vitro and some animal models have shown that quercetin, a polyphenol derived from plants, has a wide range of biological actions including anti-carcinogenic, anti-inflammatory and antiviral activities; as well as attenuating lipid peroxidation, platelet aggregation and capillary permeability. This review focuses on the physicochemical properties, dietary sources, absorption, bioavailability and metabolism of quercetin, especially main effects of quercetin on inflammation and immune function. According to the results obtained both in vitro and in vivo, good perspectives have been opened for quercetin. Nevertheless, further studies are needed to better characterize the mechanisms of action underlying the beneficial effects of quercetin on inflammation and immunity. PMID:26999194

  1. In vitro digestion and lactase treatment influence uptake of quercetin and quercetin glucoside by the Caco-2 cell monolayer

    PubMed Central

    Boyer, Jeanelle; Brown, Dan; Liu, Rui Hai

    2005-01-01

    Background Quercetin and quercetin glycosides are widely consumed flavonoids found in many fruits and vegetables. These compounds have a wide range of potential health benefits, and understanding the bioavailability of flavonoids from foods is becoming increasingly important. Methods This study combined an in vitro digestion, a lactase treatment and the Caco-2 cell model to examine quercetin and quercetin glucoside uptake from shallot and apple homogenates. Results The in vitro digestion alone significantly decreased quercetin aglycone recovery from the shallot digestate (p < 0.05), but had no significant effect on quercetin-3-glucoside recovery (p > 0.05). Digestion increased the Caco-2 cell uptake of shallot quercetin-4'-glucoside by 2-fold when compared to the non-digested shallot. Despite the loss of quercetin from the digested shallot, the bioavailability of quercetin aglycone to the Caco-2 cells was the same in both the digested and non-digested shallot. Treatment with lactase increased quercetin recovery from the shallot digestate nearly 10-fold and decreased quercetin-4'-glucoside recovery by more than 100-fold (p < 0.05), but had no effect on quercetin recovery from apple digestates. Lactase treatment also increased shallot quercetin bioavailability to the Caco-2 cells approximately 14-fold, and decreased shallot quercetin-4'-glucoside bioavailability 23-fold (p < 0.05). These Caco-2 cells had lactase activity similar to that expressed by a lactose intolerant human. Conclusions The increase in quercetin uptake following treatment with lactase suggests that dietary supplementation with lactase may increase quercetin bioavailability in lactose intolerant humans. Combining the digestion, the lactase treatment and the Caco-2 cell culture model may provide a reliable in vitro model for examining flavonoid glucoside bioavailability from foods. PMID:15644141

  2. Quercetin-induced apoptosis prevents EBV infection.

    PubMed

    Lee, Minjung; Son, Myoungki; Ryu, Eunhyun; Shin, Yu Su; Kim, Jong Gwang; Kang, Byung Woog; Cho, Hyosun; Kang, Hyojeung

    2015-05-20

    Epstein-Barr virus (EBV) is a human gamma-1 herpesvirus that establishes a lifelong latency in over 90% of the world's population. During latency, virus exists predominantly as a chromatin-associated, multicopy episome in the nuclei of a variety of tumor cells derived from B cells, T cells, natural killer (NK) cells, and epithelial cells. Licorice is the root of Glycyrrhiza uralensis or G. glabra that has traditionally cultivated in eastern part of Asia. Licorice was reported to have anti-viral, anti-inflammatory, anti-atopic, hepatoprotective, anti-neurodegenerative, anti-tumor, anti-diabetic effects and so forth. Quercetin and isoliquiritigenin are produced from licorice and highly similar in molecular structure. They have diverse bioactive effects such as antiviral activity, anti-asthmatic activity, anti-cancer activity, anti-inflammation activity, monoamine-oxidase inhibitor, and etc. To determine anti-EBV and anti-EBVaGC (Epstein-Barr virus associated gastric carcinoma) effects of licorice, we investigated antitumor and antiviral effects of quercetin and isoliquiritigenin against EBVaGC. Although both quercetin and isoliquiritigenin are cytotoxic to SNU719 cells, quercetin induced more apoptosis in SNU719 cells than isoliquiritigenin, more completely eliminated DNMT1 and DNMT3A expressions than isoliquiritigenin, and more strongly affects the cell cycle progression of SNU719 than isoliquiritigenin. Both quercetin and isoliquiritigenin induce signal transductions to stimulate apoptosis, and induce EBV gene transcription. Quercetin enhances frequency of F promoter use, whereas isoliquiritigenin enhances frequency of Q promoter use. Quercetin reduces EBV latency, whereas isoliquiritigenin increases the latency. Quercetin increases more the EBV progeny production, and inhibits more EBV infection than isoliquiritigenin. These results indicate that quercetin could be a promising candidate for antiviral and antitumor agents against EBV and human gastric carcinoma.

  3. Quercetin-induced apoptosis prevents EBV infection

    PubMed Central

    Lee, Minjung; Son, Myoungki; Ryu, Eunhyun; Shin, Yu Su; Kim, Jong Gwang; Kang, Byung Woog; Sung, Gi-Ho; Cho, Hyosun; Kang, Hyojeung

    2015-01-01

    Epstein-Barr virus (EBV) is a human gamma-1 herpesvirus that establishes a lifelong latency in over 90% of the world's population. During latency, virus exists predominantly as a chromatin-associated, multicopy episome in the nuclei of a variety of tumor cells derived from B cells, T cells, natural killer (NK) cells, and epithelial cells. Licorice is the root of Glycyrrhiza uralensis or G. glabra that has traditionally cultivated in eastern part of Asia. Licorice was reported to have anti-viral, anti-inflammatory, anti-atopic, hepatoprotective, anti-neurodegenerative, anti-tumor, anti-diabetic effects and so forth. Quercetin and isoliquiritigenin are produced from licorice and highly similar in molecular structure. They have diverse bioactive effects such as antiviral activity, anti-asthmatic activity, anti-cancer activity, anti-inflammation activity, monoamine-oxidase inhibitor, and etc. To determine anti-EBV and anti-EBVaGC (Epstein-Barr virus associated gastric carcinoma) effects of licorice, we investigated antitumor and antiviral effects of quercetin and isoliquiritigenin against EBVaGC. Although both quercetin and isoliquiritigenin are cytotoxic to SNU719 cells, quercetin induced more apoptosis in SNU719 cells than isoliquiritigenin, more completely eliminated DNMT1 and DNMT3A expressions than isoliquiritigenin, and more strongly affects the cell cycle progression of SNU719 than isoliquiritigenin. Both quercetin and isoliquiritigenin induce signal transductions to stimulate apoptosis, and induce EBV gene transcription. Quercetin enhances frequency of F promoter use, whereas isoliquiritigenin enhances frequency of Q promoter use. Quercetin reduces EBV latency, whereas isoliquiritigenin increases the latency. Quercetin increases more the EBV progeny production, and inhibits more EBV infection than isoliquiritigenin. These results indicate that quercetin could be a promising candidate for antiviral and antitumor agents against EBV and human gastric carcinoma

  4. Quercetin Treatment Ameliorates Systemic Oxidative Stress in Cirrhotic Rats

    PubMed Central

    Vieira, Emanuelle Kerber; Bona, Silvia; Di Naso, Fábio Cangeri; Porawski, Marilene; Tieppo, Juliana; Marroni, Norma Possa

    2011-01-01

    Our aim was to investigate whether the antioxidant quercetin protects against liver injury and ameliorates the systemic oxidative stress in rats with common bile duct ligation. Secondary biliary cirrhosis was induced through 28 days of bile duct obstruction. Animals received quercetin (Q) after 14 days of obstruction. Groups of control (CO) and cirrhotic (CBDL) animals received a daily 50 mg/kg body weight i.p. injection of quercetin (CO + Q; CBDL + Q) or vehicle (CO; CBDL). Quercetin corrected the reduction in superoxide dismutase (SOD), catalase CAT, and glutathione peroxidase GPx activities and prevented the increase of thiobarbituric acid reactive substances (TBARS), aminotransferases, and alkaline phosphatase in cirrhotic animals. Quercetin administration also corrected the reduced total nitrate concentration in the liver and prevented liver fibrosis and necrosis. These effects suggest that quercetin might be a useful agent to preserve liver function and prevent systemic oxidative stress. PMID:21991520

  5. Oral bioavailability of quercetin from different quercetin glycosides in dogs.

    PubMed

    Reinboth, Marianne; Wolffram, Siegfried; Abraham, Getu; Ungemach, Fritz R; Cermak, Rainer

    2010-07-01

    Although the flavonol quercetin is used as a supplement in commercial dog food, data on quercetin bioavailability in dogs are not available. Thus, we investigated quercetin bioavailability (measured as area under the concentration-time curve) in nine adult beagle dogs at an oral dose of 10 mg/kg body weight (b.w.). The major fraction (>80 %) of flavonols circulating in blood plasma were conjugated metabolites of quercetin. The absolute bioavailability of quercetin (i.e. the fraction that reaches the systemic circulation) was only about 4 %. We also compared the oral bioavailability between the aglycone quercetin and its more often used glucorhamnoside (rutin) and 3-O-glucoside (isoquercitrin) at an equimolar dose of 30 mumol/kg b.w. (corresponding to 10 mg quercetin/kg). Quercetin and isoquercitrin were mainly absorbed in the small intestine with isoquercitrin being one and a half times more bioavailable than quercetin. Maximal plasma concentration after isoquercitrin treatment was 0.89 (sem 0.07) mumol/l. Although quercetin absorption from rutin was delayed, relative bioavailability was not lower than from the aglycone itself. The latter observation is in clear contrast to findings in human subjects, pigs or rats and might indicate that rutin is a better source of quercetin in dogs than in other species. However, potential in vivo quercetin effects beyond the gastrointestinal tract are limited by the intensive metabolism as well as by the rather low bioavailability of this flavonol.

  6. Oral and Intraperitoneal Administration of Quercetin Decreased Lymphocyte DNA Damage and Plasma Lipid Peroxidation Induced by TSA In Vivo

    PubMed Central

    Chan, Shu-Ting; Shiau, Rong-Jen; Liao, Jiunn-Wang; Yeh, Shu-Lan

    2014-01-01

    Our previous study showed that quercetin enhances the anticancer effect of trichostatin A (TSA) in xenograft mice given quercetin intraperitoneally (10 mg/kg, 3 times/week). Herein, we investigate whether quercetin administered orally exerts such an effect and prevents the cytotoxic side effects of TSA. We found that quercetin given orally (20 and 100 mg/kg, 3 times/week) failed to enhance the antitumor effect of TSA although it increased the total quercetin concentration more than quercetin administered intraperitoneally in the plasma. The compound quercetin-3-glucuronide (Q3G) increased the most. However, quercetin administered intraperitoneally increased the total quercetin level in tumor tissues more than oral quercetin. Oral and intraperitoneal administration of quercetin similarly decreased lymphocyte DNA damage and plasma lipid peroxidation level induced by TSA. Furthermore, we found that the enhancing effect of Q3G on the antitumor effect of TSA and the incorporation of Q3G was less than that of quercetin in A549 cells. However, we found that A549 cells possessed the ability to convert Q3G to quercetin. In conclusion, different from quercetin administered intraperitoneally, quercetin administered orally failed to enhance the antitumor effect of TSA because of its metabolic conversion. However, it prevented TSA-induced DNA damage and lipid peroxidation. PMID:24868531

  7. Evaluation of tolerable levels of dietary quercetin for exerting its antioxidative effect in high cholesterol-fed rats.

    PubMed

    Azuma, Keiko; Ippoushi, Katsunari; Terao, Junji

    2010-04-01

    The tolerable level of dietary quercetin for exerting its antioxidative effect was evaluated in high cholesterol-fed rats, using quercetin-containing diets (31-1260 mg quercetin/kg body weight/day) and onion diets (19-94 mg quercetin aglycone equivalent/kg body weight/day), from the viewpoint of a safety assessment. After feeding for 4 weeks, the urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) levels of the quercetin-containing diet groups fed more than 157 mg quercetin/kg body weight/day were higher than the group fed a quercetin-free diet, although the plasma quercetin metabolite levels and plasma antioxidative activity were elevated depending on the amounts of quercetin or onion diet intake. No significant effect on body weight gain by quercetin-containing diets or onion diets was observed. However, ratios of the liver and kidney weights to the body weight were significantly increased in the quercetin-containing diet groups fed more than 314 mg and 157 mg quercetin/kg body weight/day, respectively, and in the onion diet groups fed more than 47 mg quercetin aglycone equivalent/kg body weight/day. These results indicated that the tolerable level for dietary quercetin for exerting its antioxidative effect was between 126 and 157 mg/kg/day for the quercetin diet and between 19 and 34 mg/kg/day for the onion diet. PMID:20138950

  8. Quercetin inhibits rhinovirus replication in vitro and in vivo.

    PubMed

    Ganesan, Shyamala; Faris, Andrea N; Comstock, Adam T; Wang, Qiong; Nanua, Suparna; Hershenson, Marc B; Sajjan, Uma S

    2012-06-01

    Rhinovirus (RV), which is responsible for the majority of common colds, also causes exacerbations in patients with asthma and chronic obstructive pulmonary disease. So far, there are no drugs available for treatment of rhinovirus infection. We examined the effect of quercetin, a plant flavanol on RV infection in vitro and in vivo. Pretreatment of airway epithelial cells with quercetin decreased Akt phosphosphorylation, viral endocytosis and IL-8 responses. Addition of quercetin 6h after RV infection (after viral endocytosis) reduced viral load, IL-8 and IFN responses in airway epithelial cells. This was associated with decreased levels of negative and positive strand viral RNA, and RV capsid protein, abrogation of RV-induced eIF4GI cleavage and increased phosphorylation of eIF2α. In mice infected with RV, quercetin treatment decreased viral replication as well as expression of chemokines and cytokines. Quercetin treatment also attenuated RV-induced airway cholinergic hyperresponsiveness. Together, our results suggest that quercetin inhibits RV endocytosis and replication in airway epithelial cells at multiple stages of the RV life cycle. Quercetin also decreases expression of pro-inflammatory cytokines and improves lung function in RV-infected mice. Based on these observations, further studies examining the potential benefits of quercetin in the prevention and treatment of RV infection are warranted.

  9. Bovine Serum Albumin Nanoparticles Containing Quercetin: Characterization and Antioxidant Activity.

    PubMed

    Antônio, Emilli; Khalil, Najeh Maissar; Mainardes, Rubiana Mara

    2016-02-01

    Quercetin is a flavonoid reported as anti-allergic, anti-inflammatory, antiplatelet, anti-microbial, antioxidant, antineurodegenerative and antitumoral. However, due to its low water solubility, its efficacy is restricted. Nanotechnology can be an importante tool to improve the quercetin properties and increase its bioavailability. In this study, bovine serum albumin (BSA) nanoparticles containing quercetin were developed by desolvation technique, characterized the mean particle size, polydispersity, zeta potential, encapsulation efficiency, physical state of drug in nanoparticles and drug release profile as well as their antioxidant activity was evaluated. The influence of glutaraldehyde percentage in nanoparticles properties was evaluated and did not influence the nanoparticles parameters. Nanoparticles presented a mean size around 130 nm and encapsulation efficiency around 85%. Results from X-ray diffractometry showed that the crystal of the drug was converted to an amorphous state in polymeric matrix. Quercetin release profile demonstrated a biphasic pattern and after 96 h approximately 18% of drug was released. Kinetic models demonstrated that the quercetin release followed a second-order model and the release was governed by Fickian diffusion. After 96 h, quercetin-loaded nanoparticles were more effective than free quercetin for scanvenger of radical ABTS + and hypochlorous acid. BSA nanoparticles represents potential carriers for improve quercetin properties. PMID:27433585

  10. Bovine Serum Albumin Nanoparticles Containing Quercetin: Characterization and Antioxidant Activity.

    PubMed

    Antônio, Emilli; Khalil, Najeh Maissar; Mainardes, Rubiana Mara

    2016-02-01

    Quercetin is a flavonoid reported as anti-allergic, anti-inflammatory, antiplatelet, anti-microbial, antioxidant, antineurodegenerative and antitumoral. However, due to its low water solubility, its efficacy is restricted. Nanotechnology can be an importante tool to improve the quercetin properties and increase its bioavailability. In this study, bovine serum albumin (BSA) nanoparticles containing quercetin were developed by desolvation technique, characterized the mean particle size, polydispersity, zeta potential, encapsulation efficiency, physical state of drug in nanoparticles and drug release profile as well as their antioxidant activity was evaluated. The influence of glutaraldehyde percentage in nanoparticles properties was evaluated and did not influence the nanoparticles parameters. Nanoparticles presented a mean size around 130 nm and encapsulation efficiency around 85%. Results from X-ray diffractometry showed that the crystal of the drug was converted to an amorphous state in polymeric matrix. Quercetin release profile demonstrated a biphasic pattern and after 96 h approximately 18% of drug was released. Kinetic models demonstrated that the quercetin release followed a second-order model and the release was governed by Fickian diffusion. After 96 h, quercetin-loaded nanoparticles were more effective than free quercetin for scanvenger of radical ABTS + and hypochlorous acid. BSA nanoparticles represents potential carriers for improve quercetin properties.

  11. UVA and UVB radiation-induced oxidation products of quercetin.

    PubMed

    Fahlman, Brian M; Krol, Ed S

    2009-12-01

    The flavonol quercetin is believed to provide protection against ultraviolet (UV) radiation-induced damage in plants. As part of our investigations into the potential for quercetin to protect skin against UV radiation-induced damage we have investigated the products of quercetin exposed to UV radiation in vitro. UVA (740 microW cm(-2) at 365 nm) or UVB (1300 microW cm(-2) at 310 nm) irradiation of quercetin in methanol results in a small conversion (less than 20%) to C-ring breakdown products over 11 h. When the triplet sensitizer benzophenone is added, greater than 90% conversion by UVA or UVB occurs within 1h. The major photoproducts from either UVA or UVB radiation are 2,4,6-trihydroxybenzaldehyde (1), 2-(3',4'-dihydroxybenzoyloxy)-4,6-dihydroxybenzoic acid (2) and 3,4-dihydroxyphenylethanol (3). Product 2 has previously been observed as a product of oxidative metabolism of quercetin, however products 1 and 3 appear to be the result of a unique UV-dependent pathway. In conclusion we have determined that quercetin undergoes slow decomposition to a mixture of C-ring-opened products, two of which to our knowledge have not been previously observed for quercetin decomposition, and that the presence of a triplet sensitizer greatly increases UV radiation-mediated quercetin decomposition. The presence of endogenous photosensitizers in the skin could potentially affect the UV stability of quercetin, suggesting that further study of quercetin for both its photoprotective properties and photostabilty in skin are warranted.

  12. Biphasic decay of the Ca transient results from increased sarcoplasmic reticulum Ca leak

    PubMed Central

    Sankaranarayanan, Rajiv; Li, Yatong; Greensmith, David J.; Eisner, David A.

    2016-01-01

    Key points Ca leak from the sarcoplasmic reticulum through the ryanodine receptor (RyR) reduces the amplitude of the Ca transient and slows its rate of decay.In the presence of β‐adrenergic stimulation, RyR‐mediated Ca leak produces a biphasic decay of the Ca transient with a fast early phase and a slow late phase.Two forms of Ca leak have been studied, Ca‐sensitising (induced by caffeine) and non‐sensitising (induced by ryanodine) and both induce biphasic decay of the Ca transient.Only Ca‐sensitising leak can be reversed by traditional RyR inhibitors such as tetracaine.Ca leak can also induce Ca waves. At low levels of leak, waves occur. As leak is increased, first biphasic decay and then slowed monophasic decay is seen. The level of leak has major effects on the shape of the Ca transient. Abstract In heart failure, a reduction in Ca transient amplitude and contractile dysfunction can by caused by Ca leak through the sarcoplasmic reticulum (SR) Ca channel (ryanodine receptor, RyR) and/or decreased activity of the SR Ca ATPase (SERCA). We have characterised the effects of two forms of Ca leak (Ca‐sensitising and non‐sensitising) on calcium cycling and compared with those of SERCA inhibition. We measured [Ca2+]i with fluo‐3 in voltage‐clamped rat ventricular myocytes. Increasing SR leak with either caffeine (to sensitise the RyR to Ca activation) or ryanodine (non‐sensitising) had similar effects to SERCA inhibition: decreased systolic [Ca2+]i, increased diastolic [Ca2+]i and slowed decay. However, in the presence of isoproterenol, leak produced a biphasic decay of the Ca transient in the majority of cells while SERCA inhibition produced monophasic decay. Tetracaine reversed the effects of caffeine but not of ryanodine. When caffeine (1 mmol l−1) was added to a cell which displayed Ca waves, the wave frequency initially increased before waves disappeared and biphasic decay developed. Eventually (at higher caffeine concentrations), the

  13. Glissandi: transient fast electrocorticographic oscillations of steadily increasing frequency, explained by temporally increasing gap junction conductance

    PubMed Central

    Cunningham, Mark O.; Roopun, Anita; Schofield, Ian S.; Whittaker, Roger G.; Duncan, Roderick; Russell, Aline; Jenkins, Alistair; Nicholson, Claire; Whittington, Miles A.; Traub, Roger D.

    2012-01-01

    Purpose We describe a form of very fast oscillation (VFO) in patient electrocorticographic (ECoG) recordings, that can occur prior to ictal events, in which the frequency increases steadily from ~30–40 Hz to >120 Hz, over a period of seconds. We dub these events “glissandi” and describe a possible model for them. Methods Four patients with epilepsy had presurgical evaluations (with ECoG obtained in two of them), and excised tissue was studied in vitro, from 3 of the patients. Glissandi were seen spontaneously in vitro, associated with ictal events; using acute slices of rat neocortex; and they were simulated using a network model of 15,000 detailed layer V pyramidal neurons, coupled by gap junctions. Key findings Glissandi were observed to arise from human temporal neocortex. In vitro, they lasted 0.2 to 4.1 seconds, prior to ictal onset. Similar events were observed in the rat in vitro, in layer V of frontal neocortex, when alkaline solution was pressure-ejected; glissandi persisted when GABAA, GABAB, and NMDA and AMPA receptors were blocked. Non-alkaline conditions, prevented glissando generation. In network simulations, it was found that steadily increasing gap junction conductance would lead to the observed steady increase in VFO field frequency. This occurred because increasing gap junction conductance shortened the time required for an action potential to cross from cell to cell. Significance The in vitro and modeling data are consistent with the hypothesis that glissandi arise when pyramidal cell gap junction conductances rise over time, possibly as a result of an alkaline fluctuation in brain pH. PMID:22686654

  14. Neuroprotective effects of quercetin in a mouse model of brain ischemic/reperfusion injury via anti-apoptotic mechanisms based on the Akt pathway.

    PubMed

    Lei, Xiaoming; Chao, Hailian; Zhang, Zhenni; Lv, Jianrui; Li, Siyuan; Wei, Haidong; Xue, Rongliang; Li, Fang; Li, Zongfang

    2015-09-01

    The present study provided experimental evidence for the neuroprotective effects of quercetin using a rat model of global brain ischemic/reperfusion (I/R) injury. Pre‑treatment with quercetin (5 or 10 mg/kg orally (p.o.); once daily) induced a dose‑dependent reduction in I/R‑induced hippocampal neuron cell loss, with 10 mg/kg/day being the lowest dose that achieved maximal neuroprotection. Administration of 10 mg/kg quercetin over at least 3 days prior to I/R was required to improve the survival rate of I/R rats. Fluorescence‑assisted cell sorting, hematoxylin and eosin staining and terminal deoxynucleotidyl transferase dUTP nick end labeling indicated neuronal cell loss in the CA1 hippocampus. Rats that had undergone transient global cerebral ischemia for 15 min followed by 1 h of reperfusion exhibited a significant increase in reactive oxygen species (ROS) production in the hippocampus. The I/R‑induced ROS overproduction in the hippocampus at 1, 12 and 24 h following I/R was significantly decreased by quercetin pre‑treatment. Western blot analysis revealed that the neuroprotective effects of quercetin (5 and 10 mg/kg/day, p.o.) were associated with an upregulation of the I/R‑induced suppression of B‑cell lymphoma‑2 (Bcl‑2), Bcl extra large and survivin expression as well as phosphorylation of Bcl‑2‑associated death promoter. Furthermore, the neuroprotective effects of quercetin (5, 10 mg/kg/day) in the brain were associated with an upregulation of Akt signaling. These findings suggested that the inhibition of I/R‑induced brain injury by quercetin likely involves a transcriptional mechanism to enhance anti‑apoptotic signaling.

  15. Transient pool boiling heat transfer due to increasing heat inputs in subcooled water at high pressures

    SciTech Connect

    Fukuda, K.; Shiotsu, M.; Sakurai, A.

    1995-09-01

    Understanding of transient boiling phenomenon caused by increasing heat inputs in subcooled water at high pressures is necessary to predict correctly a severe accident due to a power burst in a water-cooled nuclear reactor. Transient maximum heat fluxes, q{sub max}, on a 1.2 mm diameter horizontal cylinder in a pool of saturated and subcooled water for exponential heat inputs, q{sub o}e{sup t/T}, with periods, {tau}, ranging from about 2 ms to 20 s at pressures from atmospheric up to 2063 kPa for water subcoolings from 0 to about 80 K were measured to obtain the extended data base to investigate the effect of high subcoolings on steady-state and transient maximum heat fluxes, q{sub max}. Two main mechanisms of q{sub max} exist depending on the exponential periods at low subcoolings. One is due to the time lag of the hydrodynamic instability which starts at steady-state maximum heat flux on fully developed nucleate boiling (FDNB), and the other is due to the heterogenous spontaneous nucleations (HSN) in flooded cavities which coexist with vapor bubbles growing up from active cavities. The shortest period corresponding to the maximum q{sub max} for long period range belonging to the former mechanism becomes longer and the q{sub max}mechanism for long period range shifts to that due the HSN on FDNB with the increase of subcooling and pressure. The longest period corresponding to the minimum q{sub max} for the short period range belonging to the latter mechanism becomes shorter with the increase in saturated pressure. On the contrary, the longest period becomes longer with the increase in subcooling at high pressures. Correlations for steady-state and transient maximum heat fluxes were presented for a wide range of pressure and subcooling.

  16. Rapid dimerization of quercetin through an oxidative mechanism in the presence of serum albumin decreases its ability to induce cytotoxicity in MDA-MB-231 cells

    SciTech Connect

    Pham, Anh; Bortolazzo, Anthony; White, J. Brandon

    2012-10-19

    Highlights: Black-Right-Pointing-Pointer Quercetin cannot be detected intracellularly despite killing MDA-MB-231 cells. Black-Right-Pointing-Pointer Quercetin forms a heterodimer through oxidation in media with serum. Black-Right-Pointing-Pointer The quercetin heterodimer does not kill MDA-MB-231 cells. Black-Right-Pointing-Pointer Ascorbic acid stabilizes quercetin increasing cell death in quercetin treated cells. Black-Right-Pointing-Pointer Quercetin, and not a modified form, is responsible for apoptosis and cell death. -- Abstract: Quercetin is a member of the flavonoid family and has been previously shown to have a variety of anti-cancer activities. We and others have reported anti-proliferation, cell cycle arrest, and induction of apoptosis of cancer cells after treatment with quercetin. Quercetin has also been shown to undergo oxidation. However, it is unclear if quercetin or one of its oxidized forms is responsible for cell death. Here we report that quercetin rapidly oxidized in cell culture media to form a dimer. The quercetin dimer is identical to a dimer that is naturally produced by onions. The quercetin dimer and quercetin-3-O-glucopyranoside are unable to cross the cell membrane and do not kill MDA-MB-231 cells. Finally, supplementing the media with ascorbic acid increases quercetin's ability to induce cell death probably by reduction oxidative dimerization. Our results suggest that an unmodified quercetin is the compound that elicits cell death.

  17. Transient and steady State Patterns in Gravel Bars Following Sediment Supply Increases

    NASA Astrophysics Data System (ADS)

    Podolak, C.; Wilcock, P.

    2011-12-01

    Bedforms in a gravel-bed river respond to a combination of water discharge, sediment supply, and valley-scale geometry. The bed configuration can also vary between transient and steady-state conditions. Field and flume observations of gravel bedform responses to changes in sediment supply have focused primarily on decreased sediment supply, and those that have dealt with increased sediment supply have found cases of both increasing relief and decreasing relief. We present gravel bedform configurations under conditions of increased sediment supply in both field and laboratory conditions. The field study tracked the response of the Sandy River, Oregon after an increase in sediment flux due to the 2007 Marmot Dam removal in which nearly 750,000 m3 of impounded sediment which was made available for transport and resulted in a several-fold increase in annual sediment flux. The flume experiments introduced perturbation in a planar gravel bed (gravel D50 = 10mm, 15% sand) prompting alternate bar formation. Sediment was then manually added to the recirculating flume (in essence operating it as a feed flume) increasing flux rates by 50%. Upon reaching a steady state, the upstream flux was then augmented again to double the steady state rate. In response to the increased sediment supply the bed topography steepened to transport the imposed sediment flux. In both flume and field, the final bed response to increased sediment supply was deposition of a sediment wedge, steeping the channel slope with little change in bar morphology. Although the location and morphology of the bedforms were similar as the bed configuration stabilized, the transient response showed different patterns of deposition across the stream. A pattern of decreasing relief both from bar tops eroding and pools filling was observed as well as the migration of smaller wavelength high-celerity gravel bars as the bed decreased in relief. To explore the transient response we modeled both cases with a 2-D depth

  18. Maltodextrin fast dissolving films for quercetin nanocrystal delivery. A feasibility study.

    PubMed

    Lai, Francesco; Franceschini, Ilaria; Corrias, Francesco; Sala, Maria Chiara; Cilurzo, Francesco; Sinico, Chiara; Pini, Elena

    2015-05-01

    The objective of this study was to evaluate the feasibility to prepare fast dissolving films as quercetin nanocrystal delivery systems, using maltodextrins as film forming material and glycerin as plasticizer, with the goal of enhancing quercetin oral bioavailability. Quercetin nanosuspensions were prepared using a high-pressure homogenizer, and then directly used to prepare the films by a casting method. Spectroscopic and calorimetric analysis evidenced that reduction of quercetin size at nanoscale and incorporation in maltodextrin films do not affect the solid state of the active ingredient. The loading of quercetin nanocrystals into the film determined a slight variation of film elasticity and ductility. Indeed, the elastic modulus of the loaded films resulted about a half of the placebo ones, while the elongation at break increased four folds. Free and film loaded quercetin nanocrystals showed a comparable dissolution rate, much higher than that of bulk quercetin.

  19. Characterization of adsorption and electronic excited states of quercetin on titanium dioxide nanoparticles

    NASA Astrophysics Data System (ADS)

    Zdyb, Agata; Krawczyk, Stanisław

    2016-03-01

    Adsorption of quercetin on colloidal titanium dioxide nanoparticles in ethanol and its excited-state electronic structure were investigated by means of electronic and vibrational spectroscopies. The changes in electronic charge redistribution as reflected by the dipole moment difference, ∆μ, between the ground and excited electronic states were measured with electroabsorption spectroscopy and analyzed using results of TD DFT computations. Adsorption of quercetin causes a red shift of its absorption spectrum. Raman spectra of quercetin analyzed with reference to analogous data for morin indicate binding of quercetin through the hydroxy groups of the catechol moiety. The difference dipole moment, which is 5.5 D in free quercetin, increases to 11.8 D in opposite direction in adsorbed quercetin, and is associated with charge-transfer to the Ti atom. The computed transition energy, intensity, vector Δμ and molecular orbitals involved in the electronic transition at different molecular configurations indicate a bidentate chelating mode of binding of quercetin.

  20. Quercetin Attenuates Lactate Production and Extracellular Matrix Secretion in Keratoconus

    PubMed Central

    McKay, T. B.; Lyon, D.; Sarker-Nag, A.; Priyadarsini, S.; Asara, J. M.; Karamichos, D.

    2015-01-01

    Keratoconus(KC) is an ecstatic corneal disease leading to corneal-thinning and the formation of a cone-like cornea. Elevated lactate levels, increased oxidative stress, and myofibroblast formation have all been previously reported. In the current study, we assess the role of Quercetin on collagen secretion and myofibroblast formation in KC in vitro. Human corneal fibroblasts(HCFs) and human keratoconus cells(HKCs) were treated with a stable Vitamin C derivative and cultured for 4 weeks, stimulating formation of a self-assembled extracellular matrix. All samples were analyzed using Western blots and targeted tandem mass spectrometry. Our data showed that Quercetin significantly down regulates myofibroblast differentiation and fibrotic markers, such as α-smooth muscle actin (α-SMA) and Collagen III (Col III), in both HCFs and HKCs. Collagen III secretion was reduced 80% in both HCFs and HKCs following Quercetin treatment. Furthermore, Quercetin reduced lactate production by HKCs to normal HCF levels. Quercetin down regulated TGF-βR2 and TGF-β2 expression in HKCs suggesting a significant link to the TGF-β pathway. These results assert that Quercetin is a key regulator of fibrotic markers and ECM assembly by modulating cellular metabolism and TGF-β signaling. Our study suggests that Quercetin is a potential therapeutic for treatment of corneal dystrophies, such as KC. PMID:25758533

  1. Rapid dimerization of quercetin through an oxidative mechanism in the presence of serum albumin decreases its ability to induce cytotoxicity in MDA-MB-231 cells.

    PubMed

    Pham, Anh; Bortolazzo, Anthony; White, J Brandon

    2012-10-19

    Quercetin is a member of the flavonoid family and has been previously shown to have a variety of anti-cancer activities. We and others have reported anti-proliferation, cell cycle arrest, and induction of apoptosis of cancer cells after treatment with quercetin. Quercetin has also been shown to undergo oxidation. However, it is unclear if quercetin or one of its oxidized forms is responsible for cell death. Here we report that quercetin rapidly oxidized in cell culture media to form a dimer. The quercetin dimer is identical to a dimer that is naturally produced by onions. The quercetin dimer and quercetin-3-O-glucopyranoside are unable to cross the cell membrane and do not kill MDA-MB-231 cells. Finally, supplementing the media with ascorbic acid increases quercetin's ability to induce cell death probably by reduction oxidative dimerization. Our results suggest that an unmodified quercetin is the compound that elicits cell death. PMID:23000408

  2. Transient rapamycin treatment can increase lifespan and healthspan in middle-aged mice.

    PubMed

    Bitto, Alessandro; Ito, Takashi K; Pineda, Victor V; LeTexier, Nicolas J; Huang, Heather Z; Sutlief, Elissa; Tung, Herman; Vizzini, Nicholas; Chen, Belle; Smith, Kaleb; Meza, Daniel; Yajima, Masanao; Beyer, Richard P; Kerr, Kathleen F; Davis, Daniel J; Gillespie, Catherine H; Snyder, Jessica M; Treuting, Piper M; Kaeberlein, Matt

    2016-01-01

    The FDA approved drug rapamycin increases lifespan in rodents and delays age-related dysfunction in rodents and humans. Nevertheless, important questions remain regarding the optimal dose, duration, and mechanisms of action in the context of healthy aging. Here we show that 3 months of rapamycin treatment is sufficient to increase life expectancy by up to 60% and improve measures of healthspan in middle-aged mice. This transient treatment is also associated with a remodeling of the microbiome, including dramatically increased prevalence of segmented filamentous bacteria in the small intestine. We also define a dose in female mice that does not extend lifespan, but is associated with a striking shift in cancer prevalence toward aggressive hematopoietic cancers and away from non-hematopoietic malignancies. These data suggest that a short-term rapamycin treatment late in life has persistent effects that can robustly delay aging, influence cancer prevalence, and modulate the microbiome. PMID:27549339

  3. Quercetin-containing self-nanoemulsifying drug delivery system for improving oral bioavailability.

    PubMed

    Tran, Thanh Huyen; Guo, Yi; Song, Donghui; Bruno, Richard S; Lu, Xiuling

    2014-03-01

    Quercetin is a dietary flavonoid with potential chemoprotective effects, but has low bioavailability because of poor aqueous solubility and low intestinal absorption. A quercetin-containing self-nanoemulsifying drug delivery system (Q-SNEDDS) was developed to form oil-in-water nanoemulsions in situ for improving quercetin oral bioavailability. On the basis of the quercetin solubility, emulsifying ability, and stability after dispersion in an aqueous phase, an optimal SNEDDS consisting of castor oil, Tween® 80, Cremophor® RH 40, and PEG 400 (20:16:34:30, w/w) was identified. Upon mixing with water, Q-SNEDDS formed a nanoemulsion having a droplet size of 208.8 ± 4.5 nm and zeta potential of -26.3 ± 1.2 mV. The presence of Tween® 80 and PEG 400 increased quercetin solubility and maintained supersaturated quercetin concentrations (5 mg/mL) for >1 month. The optimized Q-SNEDDS significantly improved quercetin transport across a human colon carcinoma (Caco-2) cell monolayer. Fluorescence imaging demonstrated rapid absorption of the Q-SNEDDS within 40 min of oral ingestion. Following oral administration of Q-SNEDDS in rats (15 mg/kg), the area under the concentration curve and maximum concentration of plasma quercetin after 24 h increased by approximately twofold and threefold compared with the quercetin control suspension. These data suggest that this Q-SNEDDS formulation can enhance the solubility and oral bioavailability of quercetin for appropriate clinical application.

  4. Synthesis and characterization of a novel antioxidant RS4 by esterifying carboxymethyl sweetpotato starch with quercetin.

    PubMed

    Lv, Xia; Ye, Fayin; Li, Jinfeng; Ming, Jian; Zhao, Guohua

    2016-11-01

    Quercetin is grafted to carboxymethyl sweetpotato starch (CMSS) by esterification. Upon esterification, the water solubility of CMSS decreases and the CMSS-quercetin conjugates (CMSS-Q) are yellowish. FT-IR and 1H NMR indicated the covalent attachment of quercetin to CMSS. Thermogravimetry revealed the superior thermal stability of CMSS-Q over CMSS and native sweetpotato starch (NSS). The in vitro digestibility assays showed that CMSS is highly resistant to digestion while the quercetin graft with degree of substitution (DS) above 0.074 slightly increased its digestibility. The quercetin graft imparted CMSS with strong antioxidant activity and enhanced its thermal stability, which increased with quercetin DS. In vitro cyotoxicity assessment revealed that CMSS-Q is as safe as CMSS and NSS. This study showed that CMSS-Q is a novel antioxidant-resistant starch in RS4 form.

  5. Synthesis and characterization of a novel antioxidant RS4 by esterifying carboxymethyl sweetpotato starch with quercetin.

    PubMed

    Lv, Xia; Ye, Fayin; Li, Jinfeng; Ming, Jian; Zhao, Guohua

    2016-11-01

    Quercetin is grafted to carboxymethyl sweetpotato starch (CMSS) by esterification. Upon esterification, the water solubility of CMSS decreases and the CMSS-quercetin conjugates (CMSS-Q) are yellowish. FT-IR and 1H NMR indicated the covalent attachment of quercetin to CMSS. Thermogravimetry revealed the superior thermal stability of CMSS-Q over CMSS and native sweetpotato starch (NSS). The in vitro digestibility assays showed that CMSS is highly resistant to digestion while the quercetin graft with degree of substitution (DS) above 0.074 slightly increased its digestibility. The quercetin graft imparted CMSS with strong antioxidant activity and enhanced its thermal stability, which increased with quercetin DS. In vitro cyotoxicity assessment revealed that CMSS-Q is as safe as CMSS and NSS. This study showed that CMSS-Q is a novel antioxidant-resistant starch in RS4 form. PMID:27516278

  6. Quercetin 3,7-dimethyl ether: a vasorelaxant flavonoid isolated from Croton schiedeanus Schlecht.

    PubMed

    Guerrero, M F; Puebla, P; Carrón, R; Martín, M L; San Román, L

    2002-10-01

    The vasorelaxant profile of quercetin 3,7-dimethyl ether, a flavonoid isolated from Croton schiedeanus Schlecht (Euphorbiaceae), was assessed in aortic rings isolated from Wistar rats. To gain insight into its structure-activity relationship, we compared this substance with quercetin 3,4',7-trimethyl ether (ayanin), another flavonoid isolated from this plant, quercetin 3,3',4',7-tetramethyl ether, a flavonoid synthesized by us, and quercetin. In addition we examined the interaction of quercetin 3,7-dimethyl ether with the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) pathway. According to their pEC50 values (concentration producing a 50% inhibition of the maximal contractile response) to phenylephrine-induced precontraction in rat isolated aorta, the potency order was quercetin 3,7-dimethyl ether > quercetin > quercetin 3,4',7-trimethyl ether > quercetin 3,3',4',7-tetramethyl ether (4.70+/-0.18; 3.96+/-0.07; 3.64+/-0.02; 3.11+/-0.16). The relaxant effect of quercetin 3,7-dimethyl ether was significantly decreased by the removal of endothelium as well as by methylene blue, an inhibitor of guanylyl cyclase, and by N(G)-nitro-L-arginine methyl ester hydrochloride (L-NAME), an NO-synthase inhibitor. Therefore, quercetin 3,7-dimethyl ether has a NO/cGMP pathway-related profile, with increased vasorelaxant activity due to hydroxylation at positions 3 and 4 of the B ring. In addition, methylation at positions 3 and 7 with respect to quercetin of the C and A rings, respectively, seems to further enhance the vasorelaxant activity of quercetin 3,7-dimethyl ether.

  7. Simultaneous ingestion of high-methoxy pectin from apple can enhance absorption of quercetin in human subjects.

    PubMed

    Nishijima, Tomohiko; Takida, Yoshiki; Saito, Yasuo; Ikeda, Takayuki; Iwai, Kunihisa

    2015-05-28

    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. PMID:25865751

  8. Simultaneous ingestion of high-methoxy pectin from apple can enhance absorption of quercetin in human subjects.

    PubMed

    Nishijima, Tomohiko; Takida, Yoshiki; Saito, Yasuo; Ikeda, Takayuki; Iwai, Kunihisa

    2015-05-28

    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.

  9. Quercetin reduces susceptibility to influenza infection following stressful exercise.

    PubMed

    Davis, J M; Murphy, E A; McClellan, J L; Carmichael, M D; Gangemi, J D

    2008-08-01

    Exercise stress is associated with increased risk for upper respiratory tract infection. We have shown that exercise stress can increase susceptibility to infection. Quercetin, a flavonoid present in a wide variety of fruits and vegetables, has been reported to inhibit infectivity and replication of a broad spectrum of viruses and may offset the increase in susceptibility to infection associated with stressful exercise. This study examined the effects of quercetin feedings on susceptibility to the influenza virus A/Puerto Rico/8/34 (H1N1) following stressful exercise. Mice were randomly assigned to one of four treatment groups: exercise-placebo, exercise-quercetin, control-placebo, or control-quercetin. Exercise consisted of a run to fatigue (approximately 140 min) on a treadmill for 3 consecutive days. Quercetin (12.5 mg/kg) was administered via gavage for 7 days before viral challenge. At 30 min after the last bout of exercise or rest, mice (n=23-30) were intranasally inoculated with a standardized dose of influenza virus (0.04 hemagglutinating units). Mice were monitored daily for morbidity (time to sickness), symptom severity, and mortality (time to death) for 21 days. Exercise stress was associated with an increased susceptibility to infection [morbidity, mortality, and symptom severity on days 5-7 (P<0.05)]; quercetin offset the increase in susceptibility to infection [morbidity, mortality, and symptom severity on days 5-7 (P<0.05)] that was associated with stressful exercise. These data suggest that short-term quercetin feedings may prove to be an effective strategy to lessen the impact of stressful exercise on susceptibility to respiratory infection.

  10. Transient rapamycin treatment can increase lifespan and healthspan in middle-aged mice

    PubMed Central

    Bitto, Alessandro; Ito, Takashi K; Pineda, Victor V; LeTexier, Nicolas J; Huang, Heather Z; Sutlief, Elissa; Tung, Herman; Vizzini, Nicholas; Chen, Belle; Smith, Kaleb; Meza, Daniel; Yajima, Masanao; Beyer, Richard P; Kerr, Kathleen F; Davis, Daniel J; Gillespie, Catherine H; Snyder, Jessica M; Treuting, Piper M; Kaeberlein, Matt

    2016-01-01

    The FDA approved drug rapamycin increases lifespan in rodents and delays age-related dysfunction in rodents and humans. Nevertheless, important questions remain regarding the optimal dose, duration, and mechanisms of action in the context of healthy aging. Here we show that 3 months of rapamycin treatment is sufficient to increase life expectancy by up to 60% and improve measures of healthspan in middle-aged mice. This transient treatment is also associated with a remodeling of the microbiome, including dramatically increased prevalence of segmented filamentous bacteria in the small intestine. We also define a dose in female mice that does not extend lifespan, but is associated with a striking shift in cancer prevalence toward aggressive hematopoietic cancers and away from non-hematopoietic malignancies. These data suggest that a short-term rapamycin treatment late in life has persistent effects that can robustly delay aging, influence cancer prevalence, and modulate the microbiome. DOI: http://dx.doi.org/10.7554/eLife.16351.001 PMID:27549339

  11. The inconstancy of the transient climate response parameter under increasing CO2

    PubMed Central

    Gregory, J. M.; Andrews, T.; Good, P.

    2015-01-01

    In the Coupled Model Intercomparison Project Phase 5 (CMIP5), the model-mean increase in global mean surface air temperature T under the 1pctCO2 scenario (atmospheric CO2 increasing at 1% yr−1) during the second doubling of CO2 is 40% larger than the transient climate response (TCR), i.e. the increase in T during the first doubling. We identify four possible contributory effects. First, the surface climate system loses heat less readily into the ocean beneath as the latter warms. The model spread in the thermal coupling between the upper and deep ocean largely explains the model spread in ocean heat uptake efficiency. Second, CO2 radiative forcing may rise more rapidly than logarithmically with CO2 concentration. Third, the climate feedback parameter may decline as the CO2 concentration rises. With CMIP5 data, we cannot distinguish the second and third possibilities. Fourth, the climate feedback parameter declines as time passes or T rises; in 1pctCO2, this effect is less important than the others. We find that T projected for the end of the twenty-first century correlates more highly with T at the time of quadrupled CO2 in 1pctCO2 than with the TCR, and we suggest that the TCR may be underestimated from observed climate change. PMID:26438279

  12. Effects of dietary quercetin on female fertility in mice: implication of transglutaminase 2

    PubMed Central

    Beazley, Kelly E.; Nurminskaya, Maria

    2016-01-01

    Use of the dietary supplement quercetin is on the rise. Because previous studies imply an inhibitory effect of quercetin on male fertility, we explored the effects of this flavonoid on fertility in female mice. Birth outcomes, and ovarian morphology in 4-week-old offspring, were assessed in mice receiving dietary quercetin (5 mg kg−1 day−1) for 9 months during two breeding periods: from 2 to 6 months (prime reproductive age) and 8 to11 months of age. Quercetin increased birth spacing, leading to a 60% reduction in the number of litters, but enhanced folliculogenesis in ovaries of female offspring. While in young females quercetin caused an almost 70% increase in litter size, in older animals this effect was reversed. Consistent with the inhibitory activity of quercetin on the enzyme transglutaminase 2 (TG2), genetic ablation of TG2 in mice mirrors the effects of quercetin on birth outcomes and follicular development. Further, TG2-null mice lack responsiveness to quercetin ingestion. Our study shows for the first time that dietary quercetin can cause reduced reproductive potential in female mice and implies that TG2 may regulate ovarian ageing. PMID:25557047

  13. Running in pregnancy transiently increases postnatal hippocampal neurogenesis in the offspring

    PubMed Central

    Bick-Sander, Anika; Steiner, Barbara; Wolf, Susanne A.; Babu, Harish; Kempermann, Gerd

    2006-01-01

    Voluntary wheel running of mice in pregnancy and lactation led to a twofold increase in hippocampal precursor-cell proliferation and in the number of Prox1-expressing lineage-determined cells at postnatal day 8 (P8). At P36, the number of newly generated granule cells approximately doubled, resulting in a 40% higher total number of granule cells in pups from running dams as compared with controls. Cell proliferation at embryonic day 15 (E15), in contrast, was decreased in the progeny of exercising mice, and the birth weight was reduced. At P49, body weight had normalized, and hippocampal neurogenesis was not different between the two groups. mRNA for FGF2 was expressed at higher levels at E15 and P8 in runner pups, whereas VEGF was increased only at E15. Insulin-like growth factor did not show differences at any time point. At P36, no differences for any of the factors were found. Our data indicate that maternal behavior and physical activity affects infantile growth-factor expression and can transiently stimulate postnatal hippocampal development in the offspring. PMID:16537457

  14. Running in pregnancy transiently increases postnatal hippocampal neurogenesis in the offspring.

    PubMed

    Bick-Sander, Anika; Steiner, Barbara; Wolf, Susanne A; Babu, Harish; Kempermann, Gerd

    2006-03-01

    Voluntary wheel running of mice in pregnancy and lactation led to a twofold increase in hippocampal precursor-cell proliferation and in the number of Prox1-expressing lineage-determined cells at postnatal day 8 (P8). At P36, the number of newly generated granule cells approximately doubled, resulting in a 40% higher total number of granule cells in pups from running dams as compared with controls. Cell proliferation at embryonic day 15 (E15), in contrast, was decreased in the progeny of exercising mice, and the birth weight was reduced. At P49, body weight had normalized, and hippocampal neurogenesis was not different between the two groups. mRNA for FGF2 was expressed at higher levels at E15 and P8 in runner pups, whereas VEGF was increased only at E15. Insulin-like growth factor did not show differences at any time point. At P36, no differences for any of the factors were found. Our data indicate that maternal behavior and physical activity affects infantile growth-factor expression and can transiently stimulate postnatal hippocampal development in the offspring. PMID:16537457

  15. Evidence of transient increases of fluid pressure in SAFOD phase III cores

    NASA Astrophysics Data System (ADS)

    Mittempergher, S.; di Toro, G.; Gratier, J.; Hadizadeh, J.; Smith, S. A.; Spiess, R.

    2010-12-01

    In the SAFOD (San Andreas Fault Observatory at Depth) site, the activity of the San Andreas Fault includes creep and microearthquakes. Creeping is accommodated in two actively deforming gouge zones, the Southwest and the Central Deforming Zones, embedded in ~200 m wide damage zone composed of deformed sandstones, siltstones and shales. During drilling of SAFOD, no pressurized fluids were detected, although the fault and the damaged zone act as a permeability barrier to fluid circulation between the North American and Pacific plates. Microstructural, mineralogical and geochemical analysis (X-Ray Fluorescence, Field Emission Scanning Electron Microscopy, Cathodoluminescence, Electron Back Scatter Diffraction Analysis, quantitative X-Ray Powder Diffraction) of clay-rich sheared shales and arkosic sandstones associated with high angle calcite and anhydrite-bearing veins, collected at 1 m from the Southwest Deforming Zone, suggests that transient increases of pore fluid pressure have occurred, producing mode I failure in the sandstone. Such build-ups in fluid pressure may be related to permeability reduction due to dissolution of quartz and feldspar grains and passive concentration of clays in the shale layers due to pressure-solution related mass transfer. Fault parallel, low permeability seals border small fault zone patches, where fluid pressure may increase, providing a potential mechanism for the initiation of some of the microearthquakes registered in the SAFOD site.

  16. Increases of Catalase and Glutathione Peroxidase Expressions by Lacosamide Pretreatment Contributes to Neuroprotection Against Experimentally Induced Transient Cerebral Ischemia.

    PubMed

    Choi, Hyun Young; Park, Joon Ha; Chen, Bai Hui; Shin, Bich Na; Lee, Yun Lyul; Kim, In Hye; Cho, Jeong-Hwi; Lee, Tae-Kyeong; Lee, Jae-Chul; Won, Moo-Ho; Ahn, Ji Hyeon; Tae, Hyun-Jin; Yan, Bing Chun; Hwang, In Koo; Cho, Jun Hwi; Kim, Young-Myeong; Kim, Sung Koo

    2016-09-01

    Lacosamide is a new antiepileptic drug which is widely used to treat partial-onset seizures. In this study, we examined the neuroprotective effect of lacosamide against transient ischemic damage and expressions of antioxidant enzymes such as Zn-superoxide dismutase (SOD1), Mn-superoxide dismutase (SOD2), catalase (CAT) and glutathione peroxidase (GPX) in the hippocampal cornu ammonis 1 (CA1) region following 5 min of transient global cerebral ischemia in gerbils. We found that pre-treatment with 25 mg/kg lacosamide protected CA1 pyramidal neurons from transient global cerebral ischemic insult using hematoxylin-eosin staining and neuronal nuclear antigen immunohistochemistry. Transient ischemia dramatically changed expressions of SOD1, SOD2 and GPX, not CAT, in the CA1 pyramidal neurons. Lacosamide pre-treatment increased expressions of CAT and GPX, not SOD1 and 2, in the CA1 pyramidal neurons compared with controls, and their expressions induced by lacosamide pre-treatment were maintained after transient cerebral ischemia. In brief, pre-treatment with lacosamide protected hippocampal CA1 pyramidal neurons from ischemic damage induced by transient global cerebral ischemia, and the lacosamide-mediated neuroprotection may be closely related to increases of CAT and GPX expressions by lacosamide pre-treatment. PMID:27209305

  17. Transient Responses of Gravel Bars to Increases in Sediment Supply - Field & Flume

    NASA Astrophysics Data System (ADS)

    Podolak, C.

    2010-12-01

    increases in sediment supply (from the results of landslides, dam removals, or hydraulic mining) have documented both increases and decreases in topographic relief. Both field and laboratory observations suggest that the variation in relief may be a transient phase as the bed adjusts to a new equilibrium configuration.

  18. Effects of daily quercetin-rich supplementation on cardiometabolic risks in male smokers.

    PubMed

    Lee, Kyung-Hea; Park, Eunju; Lee, Hye-Jin; Kim, Myeong-Ok; Cha, Yong-Jun; Kim, Jung-Mi; Lee, Hyeran; Shin, Min-Jeong

    2011-02-01

    Limited information from human studies indicates that dietary quercetin supplementation influences blood lipid profiles, glycemic response, and inflammatory status, collectively termed cardiometabolic risks. We tested the hypothesis that quercetin-rich supplementation, derived from onion peel extract, improves cardiometabolic risk components in healthy male smokers in a randomized, double blinded, placebo-controlled parallel design. Randomly assigned subjects were instructed to take either the placebo (n = 43) or 100 mg quercetin capsules each day (n = 49) for 10 weeks. Anthropometric parameters and blood pressure were measured, and blood lipids, glucose, interleukin-6, and soluble vascular cell adhesion molecule-1 (sVCAM-1) were determined at baseline and after 10 weeks of quercetin supplementation. Quercetin-rich supplementation significantly reduced serum concentrations of total cholesterol (P < 0.05) and LDL-cholesterol (P < 0.01), whereas these effects were not shown in the placebo group. Furthermore, significant increases were observed in serum concentrations of HDL-cholesterol both in the placebo (P < 0.005) and quercetin-rich supplementation group (P < 0.001); however, changes in HDL-cholesterol were significantly greater in subjects receiving quercetin-rich supplementation than the placebo. Both systolic (P < 0.05) and diastolic blood pressure (P < 0.01) decreased significantly in the quercetin-rich supplementation group. Glucose concentrations decreased significantly after 10 weeks of quercetin-rich supplementation (P < 0.05). In contrast, no effects of quercetin-rich supplementation were observed for the inflammatory markers-IL-6 and sVCAM-1. Daily quercetin-rich supplementation from onion peel extract improved blood lipid profiles, glucose, and blood pressure, suggesting a beneficial role for quercetin as a preventive measure against cardiovascular risk. PMID:21487493

  19. Preparation and evaluation of quercetin-loaded lecithin-chitosan nanoparticles for topical delivery

    PubMed Central

    Tan, Qi; Liu, Weidong; Guo, Chenyu; Zhai, Guangxi

    2011-01-01

    Background The purpose of this study was to investigate lecithin-chitosan nanoparticles as a topical delivery system for quercetin. Methods Tocopheryl propylene glycol succinate was chosen to be the surfactant for the nanosystem. The mean particle size of the nanoparticles was 95.3 nm, and the entrapment efficiency and drug loading for quercetin were 48.5% and 2.45%, respectively. Topical delivery in vitro and in vivo of the quercetin-loaded nanoparticles was evaluated using quercetin propylene glycol solution as the control. Results Compared with quercetin solution, the quercetin-loaded nanoparticles showed higher permeation ability, and significantly increased accumulation of quercetin in the skin, especially in the epidermis. Microstructure observation of the skin surface after administration indicated that the interaction between ingredients of the nanoparticles and the skin surface markedly changed the morphology of the stratum corneum and disrupted the corneocyte layers, thus facilitating the permeation and accumulation of quercetin in skin. Conclusion Lecithin-chitosan nanoparticles are a promising carrier for topical delivery of quercetin. PMID:21904452

  20. The effects of quercetin supplementation on cognitive functioning in a community sample: a randomized, placebo-controlled trial

    PubMed Central

    Canu, Will H.; Trout, Krystal L.; Nieman, David C.

    2012-01-01

    Background: The purpose of the present study was to examine the effects of quercetin supplementation on neurocognitive functioning. Methods: A large community sample (n = 941) completed a 12-week supplementation protocol, and participants were randomly assigned to receive 500 mg/day or 1000 mg/day quercetin, or placebo. Results: Results failed to indicate significant effects of quercetin on memory, psychomotor speed, reaction time, attention, or cognitive flexibility, despite large increases in plasma quercetin levels among the quercetin treatment groups. Discussion: Consistent with recent research, this study raises concerns regarding the generalizability of positive findings of in vitro and animal quercetin research, and provides evidence that quercetin may not have an ergogenic effect on neurocognitive functioning in humans. PMID:23983966

  1. Increasing the dynamic range of a transient recorder by using two analog-to-digital converters.

    PubMed

    Beavis, R C

    1996-01-01

    This article describes an algorithm for recording transient voltages with enhanced dynamic range by using two 8-bit analog-to-digital converters (ADCs). The method requires each transient to be recorded in both ADCs, with different input voltage gains. The transients then are compared and combined to produce a single signal that has less digitization noise and greater dynamic range than signals recorded by either ADC alone and with no decrease in the sampling rate of the ADCs. The selection of operating parameters is considered and guidelines are established for the performance of this type of transient recorder. The system described here was built as a data acquisition device for a time-of-flight mass spectrometer; however, the algorithm could be applied to other types of ADC-based applications to extend their dynamic range.

  2. Dietary quercetin supplementation is not ergogenic in untrained men.

    PubMed

    Cureton, Kirk J; Tomporowski, Phillip D; Singhal, Arpit; Pasley, Jeffrey D; Bigelman, Kevin A; Lambourne, Kathleen; Trilk, Jennifer L; McCully, Kevin K; Arnaud, Maurice J; Zhao, Qun

    2009-10-01

    Quercetin supplementation increases muscle oxidative capacity and endurance in mice, but its ergogenic effect in humans has not been established. Our study investigates the effects of short-duration chronic quercetin supplementation on muscle oxidative capacity; metabolic, perceptual, and neuromuscular determinants of performance in prolonged exercise; and cycling performance in untrained men. Using a double-blind, pretest-posttest control group design, 30 recreationally active, but not endurance-trained, young men were randomly assigned to quercetin and placebo groups. A noninvasive measure of muscle oxidative capacity (phosphocreatine recovery rate using magnetic resonance spectroscopy), peak oxygen uptake (Vo(2peak)), metabolic and perceptual responses to submaximal exercise, work performed on a 10-min maximal-effort cycling test following the submaximal cycling, and voluntary and electrically evoked strength loss following cycling were measured before and after 7-16 days of supplementation with 1 g/day of quercetin in a sports hydration beverage or a placebo beverage. Pretreatment-to-posttreatment changes in phosphocreatine recovery time constant, Vo(2peak,) substrate utilization, and perception of effort during submaximal exercise, total work done during the 10-min maximal effort cycling trial, and voluntary and electrically evoked strength loss were not significantly different (P > 0.05) in the quercetin and placebo groups. Short duration, chronic dietary quercetin supplementation in untrained men does not improve muscle oxidative capacity; metabolic, neuromuscular and perceptual determinants of performance in prolonged exercise; or cycling performance. The null findings indicate that metabolic and physical performance consequences of quercetin supplementation observed in mice should not be generalized to humans.

  3. Dietary quercetin supplementation is not ergogenic in untrained men.

    PubMed

    Cureton, Kirk J; Tomporowski, Phillip D; Singhal, Arpit; Pasley, Jeffrey D; Bigelman, Kevin A; Lambourne, Kathleen; Trilk, Jennifer L; McCully, Kevin K; Arnaud, Maurice J; Zhao, Qun

    2009-10-01

    Quercetin supplementation increases muscle oxidative capacity and endurance in mice, but its ergogenic effect in humans has not been established. Our study investigates the effects of short-duration chronic quercetin supplementation on muscle oxidative capacity; metabolic, perceptual, and neuromuscular determinants of performance in prolonged exercise; and cycling performance in untrained men. Using a double-blind, pretest-posttest control group design, 30 recreationally active, but not endurance-trained, young men were randomly assigned to quercetin and placebo groups. A noninvasive measure of muscle oxidative capacity (phosphocreatine recovery rate using magnetic resonance spectroscopy), peak oxygen uptake (Vo(2peak)), metabolic and perceptual responses to submaximal exercise, work performed on a 10-min maximal-effort cycling test following the submaximal cycling, and voluntary and electrically evoked strength loss following cycling were measured before and after 7-16 days of supplementation with 1 g/day of quercetin in a sports hydration beverage or a placebo beverage. Pretreatment-to-posttreatment changes in phosphocreatine recovery time constant, Vo(2peak,) substrate utilization, and perception of effort during submaximal exercise, total work done during the 10-min maximal effort cycling trial, and voluntary and electrically evoked strength loss were not significantly different (P > 0.05) in the quercetin and placebo groups. Short duration, chronic dietary quercetin supplementation in untrained men does not improve muscle oxidative capacity; metabolic, neuromuscular and perceptual determinants of performance in prolonged exercise; or cycling performance. The null findings indicate that metabolic and physical performance consequences of quercetin supplementation observed in mice should not be generalized to humans. PMID:19679747

  4. Protective Effect of Quercetin on Posttraumatic Cardiac Injury

    PubMed Central

    Jing, Zehao; Wang, Zhuorun; Li, Xiujie; Li, Xintao; Cao, Tingting; Bi, Yue; Zhou, Jicheng; Chen, Xu; Yu, Deqin; Zhu, Liang; Li, Shuzhuang

    2016-01-01

    Quercetin is an important dietary flavonoid present in fruits and vegetables and has attracted attention because of its anti-inflammatory and anti-oxidative properties. Inflammation and oxidative stress play important roles in posttraumatic cardiomyocyte apoptosis, which contributes to secondary cardiac dysfunction. This study investigates the protective effect of quercetin on trauma-induced secondary cardiac injury and the mechanisms involved. Widely accepted nonlethal mechanical trauma models were established. In vivo, cardiomyocyte apoptosis and cardiac dysfunction in rats were assessed using TUNEL staining and a biological mechanic experiment system. In vitro, cell viability, tumour necrosis factor-α (TNF-α), reactive oxygen species (ROS) and [Ca2+]i of H9c2 cells were detected using an MTT assay, ELISA, and 2′,7′-dichlorofluorescin diacetate and fluo-4 acetoxymethyl ester assays respectively. Quercetin pretreatment (20 mg/kg i.p.; 0.5 h before trauma) significantly improved posttraumatic cardiomyocyte apoptosis and cardiac dysfunction. Pretreatment with quercetin (20 μM; 24 h before trauma plasma addition) significantly attenuated trauma-induced viability decreases, TNF-α increases, ROS overproduction and [Ca2+]i overload in H9c2 cells. In conclusion, quercetin may reverse posttraumatic cardiac dysfunction by reducing cardiomyocyte apoptosis through the suppression of TNF-α increases, ROS overproduction and Ca2+ overload in cardiomyocytes, representing a potential preventive approach for the treatment of secondary cardiac injury after mechanical trauma. PMID:27470932

  5. Transient increase in alcohol self-administration following a period of chronic exposure to corticosterone.

    PubMed

    Besheer, Joyce; Fisher, Kristen R; Lindsay, Tessa G; Cannady, Reginald

    2013-09-01

    Stressful life events and chronic stressors have been associated with escalations in alcohol drinking. Stress exposure leads to the secretion of glucocorticoids (cortisol in the human; corticosterone (CORT) in the rodent). To model a period of heightened elevations in CORT, the present work assessed the effects of chronic exposure to the stress hormone CORT on alcohol self-administration. Male Long Evans rats were trained to self-administer a sweetened alcohol solution (2% sucrose/15% alcohol) resulting in moderate levels of daily alcohol intake (0.5-0.7 g/kg). Following stable baseline operant self-administration, rats received CORT in the drinking water for 7 days. A transient increase in alcohol self-administration was observed on the first self-administration session following CORT exposure, and behavior returned to control levels by the second session. Control experiments determined that this increase in alcohol self-administration was specific to alcohol, unrelated to general motor activation, and functionally dissociated from decreased CORT levels at the time of testing. These results indicate that repeated exposure to heightened levels of stress hormone (e.g., as may be experienced during stressful episodes) has the potential to lead to exacerbated alcohol intake in low to moderate drinkers. Given that maladaptive drinking patterns, such as escalated alcohol drinking following stressful episodes, have the potential to put an individual at risk for future drinking disorders, utilization of this model will be important for examination of neuroadaptations that occur as a consequence of CORT exposure in order to better understand escalated drinking following stressful episodes in nondependent individuals. PMID:23643750

  6. Transcranial direct current stimulation transiently increases the blood-brain barrier solute permeability in vivo

    NASA Astrophysics Data System (ADS)

    Shin, Da Wi; Khadka, Niranjan; Fan, Jie; Bikson, Marom; Fu, Bingmei M.

    2016-03-01

    Transcranial Direct Current Stimulation (tDCS) is a non-invasive electrical stimulation technique investigated for a broad range of medical and performance indications. Whereas prior studies have focused exclusively on direct neuron polarization, our hypothesis is that tDCS directly modulates endothelial cells leading to transient changes in blood-brain-barrier (BBB) permeability (P) that are highly meaningful for neuronal activity. For this, we developed state-of-the-art imaging and animal models to quantify P to various sized solutes after tDCS treatment. tDCS was administered using a constant current stimulator to deliver a 1mA current to the right frontal cortex of rat (approximately 2 mm posterior to bregma and 2 mm right to sagittal suture) to obtain similar physiological outcome as that in the human tDCS application studies. Sodium fluorescein (MW=376), or FITC-dextrans (20K and 70K), in 1% BSA mammalian Ringer was injected into the rat (SD, 250-300g) cerebral circulation via the ipsilateral carotid artery by a syringe pump at a constant rate of ~3 ml/min. To determine P, multiphoton microscopy with 800-850 nm wavelength laser was applied to take the images from the region of interest (ROI) with proper microvessels, which are 100-200 micron below the pia mater. It shows that the relative increase in P is about 8-fold for small solute, sodium fluorescein, ~35-fold for both intermediate sized (Dex-20k) and large (Dex-70k) solutes, 10 min after 20 min tDCS pretreatment. All of the increased permeability returns to the control after 20 min post treatment. The results confirmed our hypothesis.

  7. Quercetin and Its Anti-Allergic Immune Response.

    PubMed

    Mlcek, Jiri; Jurikova, Tunde; Skrovankova, Sona; Sochor, Jiri

    2016-01-01

    Quercetin is the great representative of polyphenols, flavonoids subgroup, flavonols. Its main natural sources in foods are vegetables such as onions, the most studied quercetin containing foods, and broccoli; fruits (apples, berry crops, and grapes); some herbs; tea; and wine. Quercetin is known for its antioxidant activity in radical scavenging and anti-allergic properties characterized by stimulation of immune system, antiviral activity, inhibition of histamine release, decrease in pro-inflammatory cytokines, leukotrienes creation, and suppresses interleukin IL-4 production. It can improve the Th1/Th2 balance, and restrain antigen-specific IgE antibody formation. It is also effective in the inhibition of enzymes such as lipoxygenase, eosinophil and peroxidase and the suppression of inflammatory mediators. All mentioned mechanisms of action contribute to the anti-inflammatory and immunomodulating properties of quercetin that can be effectively utilized in treatment of late-phase, and late-late-phase bronchial asthma responses, allergic rhinitis and restricted peanut-induced anaphylactic reactions. Plant extract of quercetin is the main ingredient of many potential anti-allergic drugs, supplements and enriched products, which is more competent in inhibiting of IL-8 than cromolyn (anti-allergic drug disodium cromoglycate) and suppresses IL-6 and cytosolic calcium level increase. PMID:27187333

  8. Mechanisms of Neuroprotection by Quercetin: Counteracting Oxidative Stress and More

    PubMed Central

    Costa, Lucio G.; Garrick, Jacqueline M.; Roquè, Pamela J.; Pellacani, Claudia

    2016-01-01

    Increasing interest has recently focused on determining whether several natural compounds, collectively referred to as nutraceuticals, may exert neuroprotective actions in the developing, adult, and aging nervous system. Quercetin, a polyphenol widely present in nature, has received the most attention in this regard. Several studies in vitro, in experimental animals and in humans, have provided supportive evidence for neuroprotective effects of quercetin, either against neurotoxic chemicals or in various models of neuronal injury and neurodegenerative diseases. The exact mechanisms of such protective effects remain elusive, though many hypotheses have been formulated. In addition to a possible direct antioxidant effect, quercetin may also act by stimulating cellular defenses against oxidative stress. Two such pathways include the induction of Nrf2-ARE and induction of the antioxidant/anti-inflammatory enzyme paraoxonase 2 (PON2). In addition, quercetin has been shown to activate sirtuins (SIRT1), to induce autophagy, and to act as a phytoestrogen, all mechanisms by which quercetin may provide its neuroprotection. PMID:26904161

  9. Slow Erosion Rates, Increasing Relief and Transient Landscape Evolution within the Central Range of Taiwan

    NASA Astrophysics Data System (ADS)

    Ouimet, W. B.; Byrne, T. B.; Siame, L. L.; Bierman, P. R.; Rood, D.

    2013-12-01

    , low-relief topography highlight transient landscape evolution and increasing relief within portions of the Central Range of Taiwan. Thermochronologic age-elevation data collected near the low relief topography (zircon fission track and (U-Th)/He) suggest an increase in the rate of exhumation from < 1 mm/yr to ~ 3 mm/yr. at about 2 Ma. We argue that areas of subdued, low-relief topography represent a relict landscape that formed prior to the recent acceleration in rock uplift and exhumation suggested in the thermochronology data. The high-slope, landslide-dominated terrain is rapidly dissecting areas of relict topography and will eventually erase geomorphic evidence of this relict landscape.

  10. Quercetin: A flavonol with multifaceted therapeutic applications?

    PubMed

    D'Andrea, Gabriele

    2015-10-01

    Great interest is currently centered on the biologic activities of quercetin a polyphenol belonging to the class of flavonoids, natural products well known for their beneficial effects on health, long before their biochemical characterization. In particular, quercetin is categorized as a flavonol, one of the five subclasses of flavonoid compounds. Although flavonoids occur as either glycosides (with attached glycosyl groups) or as aglycones, most altogether of the dietary intake concerning quercetin is in the glycoside form. Following chewing, digestion, and absorption sugar moieties can be released from quercetin glycosides. Several organs contribute to quercetin metabolism, including the small intestine, the kidneys, the large intestine, and the liver, giving rise to glucuronidated, methylated, and sulfated forms of quercetin; moreover, free quercetin (such as aglycone) is also found in plasma. Quercetin is now largely utilized as a nutritional supplement and as a phytochemical remedy for a variety of diseases like diabetes/obesity and circulatory dysfunction, including inflammation as well as mood disorders. Owing to its basic chemical structure themost obvious feature of quercetin is its strong antioxidant activity which potentially enables it to quench free radicals from forming resonance-stabilized phenoxyl radicals. In this review the molecular, cellular, and functional bases of therapy will be emphasized taking strictly into account data appearing in the peer-reviewed literature and summarizing the main therapeutic applications of quercetin; furthermore, the drug metabolism and the main drug interaction as well as the potential toxicity will be also spotlighted.

  11. The flavonoid quercetin induces apoptosis and inhibits JNK activation in intimal vascular smooth muscle cells

    SciTech Connect

    Perez-Vizcaino, Francisco . E-mail: fperez@med.ucm.es; Bishop-Bailley, David; Lodi, Federica; Duarte, Juan; Cogolludo, Angel; Moreno, Laura; Bosca, Lisardo; Mitchell, Jane A.; Warner, Timothy D.

    2006-08-04

    Quercetin, the most abundant dietary flavonol, exerts vasodilator, anti-hypertensive, and anti-atherogenic effects and reduces the vascular remodelling associated with elevated blood pressure. Here, we have compared the effects of quercetin in intimal- and medial-type rat vascular smooth muscle cells (VSMC) in culture. After 48 h, quercetin reduced the viability of a polyclonal intimal-type cell line derived from neonatal aorta but not of a medial-type cell line derived from adult aorta. These differential effects were similar in both proliferating and quiescent VSMC. Quercetin also preferentially reduced the viability of intimal-type over medial-type VSMC in primary cultures derived from balloon-injured carotid arteries. The effects of quercetin on cell viability were mainly dependent upon induction of apoptosis, as demonstrated by nuclear condensation and fragmentation, and were unrelated to PPAR{gamma}, pro-oxidant effects or nitric oxide. The expression of MAPKs (ERK, p38, and JNK) and ERK phosphorylation were not different between intimal- and medial-type VSMC. p38 phosphorylation was negligible in both cell types. Medial-type showed a weak JNK phosphorylation while this was markedly increased in intimal-type cells. Quercetin reduced JNK phosphorylation but had no consistent effect on ERK phosphorylation. In conclusion, quercetin preferentially produced apoptosis in intimal-type compared to medial-type VSMC. This might play a role in the anti-atherogenic and anti-hypertensive effects of quercetin.

  12. Synthesis, characterization and study of antioxidant activity of quercetin-magnesium complex.

    PubMed

    Ghosh, Nilanjan; Chakraborty, Tania; Mallick, Sougata; Mana, Supriya; Singha, Deepanwita; Ghosh, Balaram; Roy, Souvik

    2015-12-01

    Quercetin (3,3',4',5,7-pentahydroxyflavone) one of the most abundant dietary flavonoids, has been investigated in the presence of magnesium (II) in methanol. The complex formation between quercetin and magnesium (II) was examined under UV-visible, Infra-red and (1)H NMR spectroscopic techniques. The spectroscopic data denoted that quercetin can reacts with magnesium cation (Mg(+2)) through the chelation site in the quercetin molecule. The free radical antioxidant activity of the complex with respect to the parent molecule was evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH) method. It was observed that the free radical scavenging activity of quercetin was increased after complexation of magnesium (Mg(+2)) cation.

  13. The critical role of quercetin in autophagy and apoptosis in HeLa cells.

    PubMed

    Wang, Yijun; Zhang, Wei; Lv, Qiongying; Zhang, Juan; Zhu, Dingjun

    2016-01-01

    In recent years, the effects of quercetin on autophagy and apoptosis of cancer cells have been widely reported, while effects on HeLa cells are still unclear. Here, HeLa cells were subjected to quercetin treatment, and then proliferation, apoptosis, and autophagy were evaluated using MTT, flow cytometry, and MDC staining, respectively. The LC3-I/II, Beclin 1, active caspase-3, and S6K1 phosphorylation were detected using Western blot assay. The ultrastructure of HeLa was observed via transmission electron microscope (TEM). Our findings showed that quercetin can dose-dependently inhibit the growth of HeLa cells. The MDC fluorescence was enhanced with increased concentration of quercetin and hit a plateau at 50 μmol/l. Western blot assay revealed that LC3-I/II ratio, Beclin 1, and active caspase-3 protein were enforced in a dose-dependent method. However, the phosphorylation of S6K1 gradually decreased, concomitant with an increase of autophagy. In addition, TEM revealed that the number of autophagic vacuoles was peaked at 50 μmol/l of quercetin. Besides, interference of autophagy with 3-MA led to proliferation inhibition and increased apoptosis in HeLa cells, accompanied by the decreased LC3-I/II conversion and the increased active caspase-3. In conclusion, quercetin can inhibit HeLa cell proliferation and induce protective autophagy at low concentrations; thus, 3-MA plus quercetin would suppress autophagy and effectively increased apoptosis.

  14. Role of quercetin in vascular physiology.

    PubMed

    Chirumbolo, Salvatore

    2012-12-01

    A recent paper in the Canadian Journal of Physiology and Pharmacology has shown that quercetin has a vascular protective effect associated with eNOS up-regulation, blood GSH redox ratio, and reduction of oxidative stress. Recent reports have recommended the consumption of quercetin, as it may contribute to a reduction in the risk of cardiovascular disease. However, the mechanisms by which quercetin exerts its action have not been fully elucidated. The majority of these mechanisms have been identified with models using animals treated with quercetin, and relatively few have been corroborated in human studies, which indicates the need for further investigation.

  15. Anode modification with capacitive materials for a microbial fuel cell: an increase in transient power or stationary power.

    PubMed

    Feng, Chunhua; Lv, Zhisheng; Yang, Xiaoshuang; Wei, Chaohai

    2014-06-14

    Extensive efforts have been devoted to improve the anode performance of a microbial fuel cell (MFC) by using modified carbon-based anode materials, but most of them did not recognize that the power performance measured by the commonly-used varying circuit resistance (VCR) or linear sweep voltammetry (LSV) method was overestimated due to the effect of anode capacitance. Here, we examined and compared the transient power and the stationary power of a series of MFCs equipped with the polypyrrole-graphene oxide (PPy-GO)-modified graphite felt anodes. It was found that noticeable transient power was recorded when the VCR or LSV method was chosen for power measurements. Calculations on the contribution of different sources to the measured maximum power density showed that the discharge of bio-electrons stored in the high-capacitance anode was a dominant contributor, especially when the time duration (for the VCR method) was not sufficiently long or the scan rate (for the LSV method) was not sufficiently low. Although anode modification with capacitive materials can result in the increased stationary power obtained from the fed-batch cycle test, owing to the increases in the anode surface area and the number of bacteria attached to anode, the increase in the transient power was more remarkable.

  16. Transient down-regulation of the RNA silencing machinery increases efficiency of Agrobacterium-mediated transformation of Arabidopsis.

    PubMed

    Bilichak, Andriy; Yao, Youli; Kovalchuk, Igor

    2014-06-01

    Agrobacterium tumefaciens is a plant pathogen that is widely used in plant transformation. As the process of transgenesis includes the delivery of single-stranded T-DNA molecule, we hypothesized that transformation rate may negatively correlate with the efficiency of the RNA-silencing machinery. Using mutants compromised in either the transcriptional or post-transcriptional gene-silencing pathways, two inhibitors of stable transformation were revealed-AGO2 and NRPD1a. Furthermore, an immunoprecipitation experiment has shown that NRPD1, a subunit of Pol IV, directly interacts with Agrobacterium T-DNA in planta. Using the Tobacco rattle virus (TRV)--based virus-induced gene silencing (VIGS) technique, we demonstrated that the transient down-regulation of the expression of either AGO2 or NRPD1a genes in reproductive organs of Arabidopsis, leads to an increase in transformation rate. We observed a 6.0- and 3.5-fold increase in transformation rate upon transient downregulation of either AGO2 or NRPD1a genes, respectively. This is the first report demonstrating the increase in the plant transformation rate via VIGS-mediated transient down-regulation of the components of epigenetic machinery in reproductive tissue.

  17. Alleviative effect of quercetin on rat testis against arsenic: a histological and biochemical study.

    PubMed

    Jahan, Sarwat; Iftikhar, Natasha; Ullah, Hizb; Rukh, Gul; Hussain, Ishtiaq

    2015-04-01

    The preventive effect of quercetin on arsenic stimulated reproductive ailments in male Sprague Dawely (SD) rats was investigated. Twenty rats were divided into four groups. The first group served as a control and was provided tap water. The second group of rats was treated with sodium arsenite at the dose of 50 ppm in drinking water. The third group served as a positive control and received an oral dose of quercetin (50 mg/kg). In the fourth group, quercetin (50 mg/kg) was co-administered orally with arsenic (50 ppm in drinking water). All the treatments were carried out for 49 days. Arsenic treatment resulted in adverse morphological and histopathological changes in testis of rats including reduced epithelial height and tubular diameter, and increased luminal diameter. In contrast, these adverse effects of arsenic were eliminated by co-administration of quercetin. Additionally arsenic treatment significantly increased testicular thiobarbituric acid reactive substance (TBARS) levels while catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), and glutathione reductase (GSR) activities, and plasma and intra-testicular testosterone concentrations, were decreased significantly. Lipid peroxidation (LPO) was significantly suppressed and depleted antioxidant defense mechanism was restored by the quercetin co-treatment. Also quercetin treatment resulted in a marked increase in plasma and testicular testosterone concentrations. On the basis of these findings, it was concluded that quercetin may be used as a potential therapeutic drug against arsenic induced reproductive toxicity. PMID:25539033

  18. Alleviative effect of quercetin on rat testis against arsenic: a histological and biochemical study.

    PubMed

    Jahan, Sarwat; Iftikhar, Natasha; Ullah, Hizb; Rukh, Gul; Hussain, Ishtiaq

    2015-04-01

    The preventive effect of quercetin on arsenic stimulated reproductive ailments in male Sprague Dawely (SD) rats was investigated. Twenty rats were divided into four groups. The first group served as a control and was provided tap water. The second group of rats was treated with sodium arsenite at the dose of 50 ppm in drinking water. The third group served as a positive control and received an oral dose of quercetin (50 mg/kg). In the fourth group, quercetin (50 mg/kg) was co-administered orally with arsenic (50 ppm in drinking water). All the treatments were carried out for 49 days. Arsenic treatment resulted in adverse morphological and histopathological changes in testis of rats including reduced epithelial height and tubular diameter, and increased luminal diameter. In contrast, these adverse effects of arsenic were eliminated by co-administration of quercetin. Additionally arsenic treatment significantly increased testicular thiobarbituric acid reactive substance (TBARS) levels while catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), and glutathione reductase (GSR) activities, and plasma and intra-testicular testosterone concentrations, were decreased significantly. Lipid peroxidation (LPO) was significantly suppressed and depleted antioxidant defense mechanism was restored by the quercetin co-treatment. Also quercetin treatment resulted in a marked increase in plasma and testicular testosterone concentrations. On the basis of these findings, it was concluded that quercetin may be used as a potential therapeutic drug against arsenic induced reproductive toxicity.

  19. Quercetin supplementation does not enhance cerebellar mitochondrial biogenesis and oxidative status in exercised rats.

    PubMed

    Casuso, Rafael A; Martínez-Amat, Antonio; Hita-Contreras, Fidel; Camiletti-Moirón, Daniel; Aranda, Pilar; Martínez-López, Emilio

    2015-07-01

    The present study tested the hypothesis that quercetin may inhibit the mitochondrial and antioxidant adaptations induced by exercise in cerebellar tissue. Thirty-five 6-week-old Wistar rats were randomly allocated into the following groups: quercetin, exercised (Q-Ex; n = 9); quercetin, sedentary (Q-Sed; n = 9); no quercetin, exercised (NQ-Ex; n = 9); and no quercetin, sedentary (NQ-Sed; n = 8). After 6 weeks of quercetin supplementation and/or exercise training, cerebellums were collected. Protein carbonyl content (PCC), sirtuin 1, peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), messenger RNA levels, citrate synthase (CS), and mitochondrial DNA were measured. When Q-Sed was compared with NQ-Sed, PCC (P < .005) showed decreased levels, whereas PGC-1α, sirtuin 1 (both, P < .01), mitochondrial DNA (P < .001), and CS (P < .01) increased. However, when Q-Ex was compared with Q-Sed, PCC showed increased levels (P < .001), whereas CS decreased (P < .01). Furthermore, the NQ-Ex group experienced an increase in PGC-1α messenger RNA levels in comparison with NQ-Sed (P > .01). This effect, however, did not appear in Q-Ex (P < .05). Therefore, we must hypothesize that either the dose (25 mg/kg) or the length of the quercetin supplementation period that was used in the present study (or perhaps both) may impair exercise-induced adaptations in cerebellar tissue. PMID:26032482

  20. Bioavailability of the flavonol quercetin in cows after intraruminal application of quercetin aglycone and rutin.

    PubMed

    Berger, L M; Wein, S; Blank, R; Metges, C C; Wolffram, S

    2012-09-01

    The bioavailability of quercetin has been intensively investigated in monogastric species, but knowledge about its bioavailability in ruminants does not exist. Thus, the aim of the present study was to determine the bioavailability of quercetin in nonlactating cows equipped with indwelling catheters placed in one jugular vein after intraruminal and additionally after i.v. application, respectively. Quercetin was administered intraruminally in equimolar amounts, either in the aglycone form or as its glucorhamnoside rutin, each at 2 dosages [10 and 50 mg of quercetin/kg of body weight (BW)]. In a second trial, 0.8 mg of quercetin aglycone/kg of BW was applied i.v. Blood samples were drawn 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 h after intraruminal application and every 5 min (first hour), every 10 min(second hour), and at 3 and 6h after i.v. bolus application, respectively. Quercetin and quercetin metabolites with an intact flavonol structure (isorhamnetin, tamarixetin, and kaempferol) in plasma samples were analyzed by HPLC with fluorescence detection. After intraruminal application of quercetin and rutin, respectively, quercetin and its methylated (isorhamnetin, tamarixetin) and dehydroxylated (kaempferol) derivatives were present in plasma mainly as conjugated forms, whereas free quercetin and its derivatives were scarcely detected. For rutin, the relative bioavailability of total flavonols (sum of conjugated and nonconjugated quercetin and its conjugated and nonconjugated derivatives after intake of 50 mg/kg of BW) was 767.3% compared with quercetin aglycone (100%). Absolute bioavailability of total flavonols was only 0.1 and 0.5% after quercetin aglycone and rutin applications, respectively. Our data demonstrate that bioavailability of quercetin from rutin is substantially higher compared with that from quercetin aglycone in cows after intraruminal (or oral) application, unlike in monogastric species. PMID:22916908

  1. ATF936, a novel oral calcilytic, increases bone mineral density in rats and transiently releases parathyroid hormone in humans.

    PubMed

    John, Markus R; Widler, Leo; Gamse, Rainer; Buhl, Thomas; Seuwen, Klaus; Breitenstein, Werner; Bruin, Gerard J M; Belleli, Rossella; Klickstein, Lloyd B; Kneissel, Michaela

    2011-08-01

    Parathyroid hormone (PTH), when injected daily as either the intact hormone PTH(1-84) or the active fragment PTH(1-34) (teriparatide), is an efficacious bone anabolic treatment option for osteoporosis patients. Injections lead to rapid and transient spikes in hormone exposure levels, a profile which is a prerequisite to effectively form bone. Oral antagonists of the calcium-sensing receptor (calcilytics) stimulate PTH secretion and represent thus an alternative approach to elevate hormone levels transiently. We report here on ATF936, a novel calcilytic, which triggered rapid, transient spikes in endogenous PTH levels when given orally in single doses of 10 and 30mg/kg to growing rats, and of 1mg/kg to dogs. Eight weeks daily oral application of 30mg/kg of ATF936 to aged female rats induced in the proximal tibia metaphysis increases in bone mineral density, cancellous bone volume and cortical and trabecular thickness as evaluated by computed tomography. In healthy humans, single oral doses of ATF936 produced peak PTH levels in plasma after a median time of 1h and levels returned to normal at 24-h post-dose. The average maximum PTH concentration increase from baseline was 1.9, 3.6, and 6.0-fold at doses of 40, 70, and 140mg. ATF936 was well tolerated. The sharp, transient increase in PTH levels produced by the oral calcilytic ATF936 was comparable to the PTH profile observed after subcutaneous administration of teriparatide. In conclusion, ATF936 might hold potential as an oral bone-forming osteoporosis therapy.

  2. Light induces a rapid and transient increase in inositol-trisphosphate in toad rod outer segments

    SciTech Connect

    Brown, J.E.; Blazynski, C.; Cohen, A.I.

    1987-08-14

    The sub-second time course of changes in the content of (/sup 3/H)inositol-1,4,5-trisphosphate was determined in rod outer segments from very rapidly frozen Bufo retinas that had been incubated with (/sup 3/H)inositol. Rod outer segments were cut off frozen specimens with a cryostat microtome and the water soluble extracts were analyzed. The content of (/sup 3/H)inositol-1,4,5-trisphosphate rose after approximately 250 msec of bright illumination, but returned to the unstimulated level after 1 sec, whether the stimulus remained on or not. That is, there was rapid but transient change in the content of (/sup 3/H)inositol-1,4,5-trisphosphate after the onset of stimulation.

  3. Effects of quercetin on the sleep-wake cycle in rats: involvement of gamma-aminobutyric acid receptor type A in regulation of rapid eye movement sleep.

    PubMed

    Kambe, Daiji; Kotani, Makiko; Yoshimoto, Makoto; Kaku, Shinsuke; Chaki, Shigeyuki; Honda, Kazuki

    2010-05-12

    The bioflavonoid quercetin is widely found in plants and exerts a large number of biological activities such as anti-hypertensive and anti-inflammatory properties. However, the effect of quercetin on the sleep-wake cycle has not been investigated. In the present study, we investigated the effect of quercetin on sleep-wake regulation. Intraperitoneal administration of quercetin (200mg/kg) significantly increased non-rapid eye movement (non-REM) sleep during dark period in rats, while it significantly decreased REM sleep. The decrease in REM sleep induced by quercetin was blocked by intracerebroventricular (i.c.v.) injection of bicuculline, a GABA(A) receptor antagonist. In contrast, the increase in non-REM sleep induced by quercetin was not affected by i.c.v. injection of bicuculline. Therefore, the present results suggest that quercetin alters the sleep-wake cycle partly through activation of GABA(A) receptors.

  4. Protective mechanism of quercetin on acute myocardial infarction in rats.

    PubMed

    Li, B; Yang, M; Liu, J W; Yin, G T

    2016-03-11

    To investigate the protective mechanism of quercetin on acute myocardial infarction (AMI) rats, an AMI rat model was established by ligating the left coronary anterior descending branch. The rats were randomly divided into the model group and low- and high-dose quercetin groups. The control group comprised sham-operated rats. The rats in the low- and high-dose quercetin groups were administered 100 and 400 mg/kg quercetin, respectively, by gavage. The rats in the control and model groups were administered isometric normal saline once daily for one week. The mRNA and protein levels of TNF-α and IL-1β in the myocardial tissue of rats were detected in each group by real time polymerase chain reaction and enzyme-linked immunosorbent assay. Malondialdehyde (MDA) content in the myocardial tissue and superoxide dismutase (SOD) and catalase (CAT) activities were detected using a colorimetric method. The level of apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling. Compared with those in the control group, the mRNA and protein levels of TNF-α, IL-1β and MDA content in the model, low-, and high-dose groups significantly increased. SOD and CAT activities decreased significantly. The cell apoptosis index increased significantly  (P < 0.05). Compared with those in the model group, the mRNA and protein levels of TNF-α and IL-1β and MDA content in myocardial tissue of rats in the low-dose and high-dose groups decreased significantly. SOD and CAT activities increased significantly. The cell apoptosis index significantly reduced (P < 0.05). In conclusion, quercetin has significant anti-inflammatory, antioxidant, and anti-apoptotic effects on AMI rats and can effectively protect against myocardium damage.

  5. Quercetin and the mitochondria: A mechanistic view.

    PubMed

    de Oliveira, Marcos Roberto; Nabavi, Seyed Mohammad; Braidy, Nady; Setzer, William N; Ahmed, Touqeer; Nabavi, Seyed Fazel

    2016-01-01

    Quercetin is an important flavonoid that is ubiquitously present in the diet in a variety of fruits and vegetables. It has been traditionally viewed as a potent antioxidant and anti-inflammatory molecule. However, recent studies have suggested that quercetin may exert its beneficial effects independent of its free radical-scavenging properties. Attention has been placed on the effect of quercetin on an array of mitochondrial processes. Quercetin is now recognized as a phytochemical that can modulate pathways associated with mitochondrial biogenesis, mitochondrial membrane potential, oxidative respiration and ATP anabolism, intra-mitochondrial redox status, and subsequently, mitochondria-induced apoptosis. The present review evaluates recent evidence on the ability of quercetin to interact with the abovementioned pathways, and critically analyses how, such interactions can exert protection against mitochondrial damage in response to toxicity induced by several exogenously and endogenously-produced cellular stressors, and oxidative stress in particular. PMID:26740171

  6. Transient temperature and sea level response of a two-dimensional ocean-climate model to greenhouse gas increases

    SciTech Connect

    Harvey, L.D.D.

    1994-09-01

    A two-dimensional dynamical ocean model is coupled to an energy balance climate model and used to investigate the transient surface temperature and sea level response to greenhouse gas increases. For most experiments a step function surface-troposphere heating perturbation of 6 W/sq m is applied. A transient reduction in the thermohaline overturning flux of 15-30% occurs in most experiments, although in some cases a near-total circulation collapse occurs within the first 100 years and lasts 700-1000 years. The transient circulation decrease is attributed to the greater rate of downward penetration of the heating anomaly in downwelling rather than in upwelling regions and is not a result of reduced convection. For experiments in which the steady state circulation is qualitatively unchanged after a heating perturbation, the surface temperature response is roughly uniform with latitude, in the absence of ice and snow. However, in some cases a heating perturbation induces the transition from a one-cell to a two-cell overturning circulation, or causes a complete reversal in the direction of overturning when a single cell spans both hemispheres, causing marked latitudinal variations in the surface temperature response.

  7. Quercetin, a Natural Flavonoid Interacts with DNA, Arrests Cell Cycle and Causes Tumor Regression by Activating Mitochondrial Pathway of Apoptosis

    PubMed Central

    Srivastava, Shikha; Somasagara, Ranganatha R.; Hegde, Mahesh; Nishana, Mayilaadumveettil; Tadi, Satish Kumar; Srivastava, Mrinal; Choudhary, Bibha; Raghavan, Sathees C.

    2016-01-01

    Naturally occurring compounds are considered as attractive candidates for cancer treatment and prevention. Quercetin and ellagic acid are naturally occurring flavonoids abundantly seen in several fruits and vegetables. In the present study, we evaluate and compare antitumor efficacies of quercetin and ellagic acid in animal models and cancer cell lines in a comprehensive manner. We found that quercetin induced cytotoxicity in leukemic cells in a dose-dependent manner, while ellagic acid showed only limited toxicity. Besides leukemic cells, quercetin also induced cytotoxicity in breast cancer cells, however, its effect on normal cells was limited or none. Further, quercetin caused S phase arrest during cell cycle progression in tested cancer cells. Quercetin induced tumor regression in mice at a concentration 3-fold lower than ellagic acid. Importantly, administration of quercetin lead to ~5 fold increase in the life span in tumor bearing mice compared to that of untreated controls. Further, we found that quercetin interacts with DNA directly, and could be one of the mechanisms for inducing apoptosis in both, cancer cell lines and tumor tissues by activating the intrinsic pathway. Thus, our data suggests that quercetin can be further explored for its potential to be used in cancer therapeutics and combination therapy. PMID:27068577

  8. Effect of quercetin on nicotine-induced biochemical changes and DNA damage in rat peripheral blood lymphocytes.

    PubMed

    Muthukumaran, Shanmugavelu; Sudheer, Adluri Ram; Nalini, Namasivayam; Menon, Venugopal Padmanabhan

    2008-01-01

    We elucidated the protective effect of quercetin, a polyphenolic flavonoid, on lipid peroxidation, endogenous antioxidant status and DNA damage during nicotine-induced toxicity in cultured rat peripheral blood lymphocytes as compared to N-acetylcysteine (NAC), a well-known antioxidant. Lymphocytes were exposed to nicotine (3 mM) with and without quercetin and NAC (1 mM) in RPMI-1640 medium for 1 h. In preliminary experiments to fix the effective dose of quercetin, different doses of quercetin (25, 50, 75, 100 and 200 microM) were administered to lymphocytes with nicotine, and lipid peroxidation markers (thiobarbituric acid reactive substances and hydroperoxides) were analysed. A 75 microM dose of quercetin was found to be effective as evidenced by decreased lipid peroxidation. To evaluate the protective potential of quercetin against genotoxic effects of nicotine we used comet and micronucleus assays, which are valid parameters to assess genetic damage. In addition, biochemical changes including lipid peroxidation and antioxidant status were assessed. There were significant increases in the levels of lipid peroxidation, comet parameters and micronuclei frequencies, followed by decrease in the endogenous antioxidant status, in nicotine-treated lymphocytes, which were brought back to near normal by quercetin or NAC treatment. The protective effect of quercetin against nicotine toxicity was comparable to that of NAC. These findings suggest that quercetin can be as effective as NAC in protecting rat peripheral lymphocytes against nicotine-induced cellular and DNA damage. PMID:18796241

  9. Quercetin, a Natural Flavonoid Interacts with DNA, Arrests Cell Cycle and Causes Tumor Regression by Activating Mitochondrial Pathway of Apoptosis.

    PubMed

    Srivastava, Shikha; Somasagara, Ranganatha R; Hegde, Mahesh; Nishana, Mayilaadumveettil; Tadi, Satish Kumar; Srivastava, Mrinal; Choudhary, Bibha; Raghavan, Sathees C

    2016-01-01

    Naturally occurring compounds are considered as attractive candidates for cancer treatment and prevention. Quercetin and ellagic acid are naturally occurring flavonoids abundantly seen in several fruits and vegetables. In the present study, we evaluate and compare antitumor efficacies of quercetin and ellagic acid in animal models and cancer cell lines in a comprehensive manner. We found that quercetin induced cytotoxicity in leukemic cells in a dose-dependent manner, while ellagic acid showed only limited toxicity. Besides leukemic cells, quercetin also induced cytotoxicity in breast cancer cells, however, its effect on normal cells was limited or none. Further, quercetin caused S phase arrest during cell cycle progression in tested cancer cells. Quercetin induced tumor regression in mice at a concentration 3-fold lower than ellagic acid. Importantly, administration of quercetin lead to ~5 fold increase in the life span in tumor bearing mice compared to that of untreated controls. Further, we found that quercetin interacts with DNA directly, and could be one of the mechanisms for inducing apoptosis in both, cancer cell lines and tumor tissues by activating the intrinsic pathway. Thus, our data suggests that quercetin can be further explored for its potential to be used in cancer therapeutics and combination therapy. PMID:27068577

  10. Quercetin inhibits intestinal iron absorption and ferroportin transporter expression in vivo and in vitro.

    PubMed

    Lesjak, Marija; Hoque, Rukshana; Balesaria, Sara; Skinner, Vernon; Debnam, Edward S; Srai, Surjit K S; Sharp, Paul A

    2014-01-01

    Balancing systemic iron levels within narrow limits is critical for maintaining human health. There are no known pathways to eliminate excess iron from the body and therefore iron homeostasis is maintained by modifying dietary absorption so that it matches daily obligatory losses. Several dietary factors can modify iron absorption. Polyphenols are plentiful in human diet and many compounds, including quercetin--the most abundant dietary polyphenol--are potent iron chelators. The aim of this study was to investigate the acute and longer-term effects of quercetin on intestinal iron metabolism. Acute exposure of rat duodenal mucosa to quercetin increased apical iron uptake but decreased subsequent basolateral iron efflux into the circulation. Quercetin binds iron between its 3-hydroxyl and 4-carbonyl groups and methylation of the 3-hydroxyl group negated both the increase in apical uptake and the inhibition of basolateral iron release, suggesting that the acute effects of quercetin on iron transport were due to iron chelation. In longer-term studies, rats were administered quercetin by a single gavage and iron transporter expression measured 18 h later. Duodenal FPN expression was decreased in quercetin-treated rats. This effect was recapitulated in Caco-2 cells exposed to quercetin for 18 h. Reporter assays in Caco-2 cells indicated that repression of FPN by quercetin was not a transcriptional event but might be mediated by miRNA interaction with the FPN 3'UTR. Our study highlights a novel mechanism for the regulation of iron bioavailability by dietary polyphenols. Potentially, diets rich in polyphenols might be beneficial for patients groups at risk of iron loading by limiting the rate of intestinal iron absorption. PMID:25058155

  11. Quercetin Inhibits Intestinal Iron Absorption and Ferroportin Transporter Expression In Vivo and In Vitro

    PubMed Central

    Balesaria, Sara; Skinner, Vernon; Debnam, Edward S.; Srai, Surjit K. S.; Sharp, Paul A.

    2014-01-01

    Balancing systemic iron levels within narrow limits is critical for maintaining human health. There are no known pathways to eliminate excess iron from the body and therefore iron homeostasis is maintained by modifying dietary absorption so that it matches daily obligatory losses. Several dietary factors can modify iron absorption. Polyphenols are plentiful in human diet and many compounds, including quercetin – the most abundant dietary polyphenol – are potent iron chelators. The aim of this study was to investigate the acute and longer-term effects of quercetin on intestinal iron metabolism. Acute exposure of rat duodenal mucosa to quercetin increased apical iron uptake but decreased subsequent basolateral iron efflux into the circulation. Quercetin binds iron between its 3-hydroxyl and 4-carbonyl groups and methylation of the 3-hydroxyl group negated both the increase in apical uptake and the inhibition of basolateral iron release, suggesting that the acute effects of quercetin on iron transport were due to iron chelation. In longer-term studies, rats were administered quercetin by a single gavage and iron transporter expression measured 18 h later. Duodenal FPN expression was decreased in quercetin-treated rats. This effect was recapitulated in Caco-2 cells exposed to quercetin for 18 h. Reporter assays in Caco-2 cells indicated that repression of FPN by quercetin was not a transcriptional event but might be mediated by miRNA interaction with the FPN 3′UTR. Our study highlights a novel mechanism for the regulation of iron bioavailability by dietary polyphenols. Potentially, diets rich in polyphenols might be beneficial for patients groups at risk of iron loading by limiting the rate of intestinal iron absorption. PMID:25058155

  12. Steady and transient forced convection heat transfer for water flowing in small tubes with exponentially increasing heat inputs

    NASA Astrophysics Data System (ADS)

    Shibahara, M.; Fukuda, K.; Liu, Q. S.; Hata, K.

    2016-06-01

    Steady and transient heat transfer coefficients for water flowing in small tubes with exponentially increasing heat inputs were measured. Platinum tubes with inner diameters of 1.0 and 2.0 mm were used as test tubes, which were mounted vertically in the experimental water loop. In the experiment, the upward flow velocity ranged from 2 to 16 m/s, and the corresponding Reynolds numbers ranged from 4.77 × 103 to 9.16 × 104 at the inlet liquid temperatures ranged from 298 to 343 K. The heat generation rate exponentially increased with the function. The period of the heat generation rate ranged from 24 ms to 17.5 s. Experimental results indicate that steady heat transfer coefficients decreased with the increase in the inner diameter of the small tube. Moreover, the ratio of bulk viscosity to near-wall viscosity of water increased with the rise in surface temperature of the vertical tube. From the experimental data, correlations of steady-state heat transfer for inner diameters of 1.0 and 2.0 mm were obtained. The heat transfer coefficient increased with decreasing the period of the heat generation rate as the flow velocity decreased. Moreover, the Nusselt number under the transient condition was affected by the Fourier number and the Reynolds number.

  13. Effects of rutin and quercetin on monooxygenase activities in experimental influenza virus infection.

    PubMed

    Savov, Varban M; Galabov, Angel S; Tantcheva, Lyubka P; Mileva, Milka M; Pavlova, Elitsa L; Stoeva, Emilia S; Braykova, Ana A

    2006-08-01

    The aim of this work is to study the effect of the flavonoids rutin and quercetin on hepatic monooxygenase activities in experimental influenza virus infection (EIVI). EIVI causes oxidative stress in the whole organism. This is confirmed by the rapidly increased concentrations of thiobarbituric reactive substances in influenza-infected mice: lungs - 290%; blood plasma - more than 320%; liver - 230%; brain - 50%. Although known for their antioxidant activities, rutin and quercetin exhibit prooxidant effect in healthy and antioxidant activity in influenza-infected animals. The pretreatment with both flavonoids (20 mg/kg b.w.) restores oxidative damage mostly in the target organ of the infection as well as in the liver of all infected mice (lungs: rutin - 30%, quercetin - 40%, combination - 45%; liver: rutin - 12%; quercetin - 40%; combination - 50%). As far as EIVI causes oxidative stress, toxicosis and inhibition of the hepatic monooxygenase activity, it is important to study the effects of rutin and quercetin on these systems. Both flavonoids induce the level of cytochrome P-450 (rutin - 13%, quercetin - 30%, combination - 22%) but inactivate NADPH-cytochrome c reductase, aminopyrine N-demethylase and analgin N-demethylase on the 5th day of EIVI. Probably, these flavonoids affect different components of the monooxygenase system. These effects could be explained with oxidative hepatic intoxication on the 5th critical day of EIVI as well as higher dose treatment. More data are needed on the antioxidant/prooxidant effects of rutin and quercetin, probably due to specific metabolic and physiological activities, chemical structure, etc.

  14. Quercetin mediated reduction of angiogenic markers and chaperones in DLA-induced solid tumours.

    PubMed

    Anand, Kushi; Asthana, Pallavi; Kumar, Anup; Ambasta, Rashmi K; Kumar, Pravir

    2011-01-01

    Diet-derived flavonoids, in particular quercetin, may play advantageous roles by preventing or/and inhibiting oncogenesis. Evidence suggests that quercetin can elicit various properties depending on the cell type. The aim of this study was to evaluate its effects on Dalton's lymphoma ascites (DLA) induced solid tumours and to identify the target(s) of action. We addressed this question by inducing subcutaneous solid tumours in Swiss albino mice and investigated whether the quercetin affects essential biological processes that are responsible for tumour growth, morphology, angiogenesis and apoptosis. We also studied influence on several heat shock proteins (HSPs). Our findings demonstrate that intra-tumour administration of quercetin results in decreased volume/weight. Furthermore, we demonstrate that quercetin promotes apoptosis of cancer cells by down-regulating the levels of Hsp90 and Hsp70. Depletion of these two chaperones by quercetin might result in triggering of caspase-3 in treated tumours. Moreover, it also down-regulated the expression of major key angiogenic or pro-angiogenic factors, like HIF-1α and VEGF In addition, H and E staining together with immunofluorescence of fixed tumour tissue provided evidence in support of increased cell death in quercetin-treated mice. PMID:22393949

  15. Onion skin waste as a valorization resource for the by-products quercetin and biosugar.

    PubMed

    Choi, In Seong; Cho, Eun Jin; Moon, Jae-Hak; Bae, Hyeun-Jong

    2015-12-01

    Onion skin waste (OSW), which is produced from processed onions, is a major industrial waste. We evaluated the use of OSW for biosugar and quercetin production. The carbohydrate content of OSW was analyzed, and the optimal conversion conditions were evaluated by varying enzyme mixtures and loading volumes for biosugar production and quercetin extraction. The enzymatic conversion rate of OSW to biosugar was 98.5% at 0.72 mg of cellulase, 0.16 mg of pectinase, and 1.0mg of xylanase per gram of dry OSW. Quercetin extraction also increased by 1.61-fold after complete enzymatic hydrolysis. In addition, the newly developed nano-matrix (terpyridine-immobilized silica-coated magnetic nanoparticles-zinc (TSMNP-Zn matrix) was utilized to separate quercetin from OSW extracts. The nano-matrix facilitated easy separation and purification of quercetin. Using the TSMNP-Zn matrix the quercetin was approximately 90% absorbed. In addition, the recovery yield of quercetin was approximately 75% after treatment with ethylenediaminetetraacetic acid.

  16. Quercetin in Cancer Treatment, Alone or in Combination with Conventional Therapeutics?

    PubMed

    Brito, Ana Filipa; Ribeiro, Marina; Abrantes, Ana Margarida; Pires, Ana Salomé; Teixo, Ricardo Jorge; Tralhão, José Guilherme; Botelho, Maria Filomena

    2015-01-01

    Cancer is a problem of global importance, since the incidence is increasing worldwide and therapeutic options are generally limited. Thus, it becomes imperative to find new therapeutic targets as well as new molecules with therapeutic potential for tumors. Flavonoids are polyphenolic compounds that may be potential therapeutic agents. Several studies have shown that these compounds have a higher anticancer potential. Among the flavonoids in the human diet, quercetin is one of the most important. In the last decades, several anticancer properties of quercetin have been described, such as cell signaling, pro-apoptotic, anti-proliferative and anti-oxidant effects, growth suppression. In fact, it is now well known that quercetin has diverse biological effects, inhibiting multiple enzymes involved in cell proliferation, as well as, in signal transduction pathways. On the other hand, there are also studies reporting potential synergistic effects when combined quercetin with chemotherapeutic agents or radiotherapy. In fact, several studies which aim to explore the anticancer potential of these combined treatments have already been published, the majority with promising results. Actually it is well known that quercetin can act on the chemosensitization and radiosensitization but also as chemoprotective and radioprotective, protecting normal cells of the side effects that results from chemotherapy and radiotherapy, which obviously provides notable advantages in their use in anticancer treatment. Thus, all these data indicate that quercetin may have a key role in anticancer treatment. In this context, this review is focused on the relationship between flavonoids and cancer, with special emphasis on the role of quercetin.

  17. Cooling treatment transiently increases the permeability of brain capillary endothelial cells through translocation of claudin-5.

    PubMed

    Inamura, Akinori; Adachi, Yasuhiro; Inoue, Takao; He, Yeting; Tokuda, Nobuko; Nawata, Takashi; Shirao, Satoshi; Nomura, Sadahiro; Fujii, Masami; Ikeda, Eiji; Owada, Yuji; Suzuki, Michiyasu

    2013-08-01

    The blood-brain-barrier (BBB) is formed by different cell types, of which brain microvascular endothelial cells are major structural constituents. The goal of this study was to examine the effects of cooling on the permeability of the BBB with reference to tight junction formation of brain microendothelial cells. The sensorimotor cortex above the dura mater in adult male Wistar rats was focally cooled to a temperature of 5 °C for 1 h, then immunostaining for immunoglobulin G (IgG) was performed to evaluate the permeability of the BBB. Permeability produced by cooling was also evaluated in cultured murine brain endothelial cells (bEnd3) based on measurement of trans-epithelial electric resistance (TEER). Immunocytochemistry and Western blotting of proteins associated with tight junctions in bEnd3 were performed to determine protein distribution before and after cooling. After focal cooling of the rat brain cortex, diffuse immunostaining for IgG was observed primarily around the small vasculature and in the extracellular spaces of parenchyma of the cortex. In cultured bEnd3, TEER significantly decreased during cooling (15 °C) and recovered to normal levels after rewarming to 37 °C. Immunocytochemistry and Western blotting showed that claudin-5, a critical regulatory protein for tight junctions, was translocated from the membrane to the cytoplasm after cooling in cultured bEnd3 cells. These results suggest that focal brain cooling may open the BBB transiently through an effect on tight junctions of brain microendothelial cells, and that therapeutically this approach may allow control of BBB function and drug delivery through the BBB.

  18. Cooling treatment transiently increases the permeability of brain capillary endothelial cells through translocation of claudin-5.

    PubMed

    Inamura, Akinori; Adachi, Yasuhiro; Inoue, Takao; He, Yeting; Tokuda, Nobuko; Nawata, Takashi; Shirao, Satoshi; Nomura, Sadahiro; Fujii, Masami; Ikeda, Eiji; Owada, Yuji; Suzuki, Michiyasu

    2013-08-01

    The blood-brain-barrier (BBB) is formed by different cell types, of which brain microvascular endothelial cells are major structural constituents. The goal of this study was to examine the effects of cooling on the permeability of the BBB with reference to tight junction formation of brain microendothelial cells. The sensorimotor cortex above the dura mater in adult male Wistar rats was focally cooled to a temperature of 5 °C for 1 h, then immunostaining for immunoglobulin G (IgG) was performed to evaluate the permeability of the BBB. Permeability produced by cooling was also evaluated in cultured murine brain endothelial cells (bEnd3) based on measurement of trans-epithelial electric resistance (TEER). Immunocytochemistry and Western blotting of proteins associated with tight junctions in bEnd3 were performed to determine protein distribution before and after cooling. After focal cooling of the rat brain cortex, diffuse immunostaining for IgG was observed primarily around the small vasculature and in the extracellular spaces of parenchyma of the cortex. In cultured bEnd3, TEER significantly decreased during cooling (15 °C) and recovered to normal levels after rewarming to 37 °C. Immunocytochemistry and Western blotting showed that claudin-5, a critical regulatory protein for tight junctions, was translocated from the membrane to the cytoplasm after cooling in cultured bEnd3 cells. These results suggest that focal brain cooling may open the BBB transiently through an effect on tight junctions of brain microendothelial cells, and that therapeutically this approach may allow control of BBB function and drug delivery through the BBB. PMID:23653089

  19. Quercetin regulates hepatic cholesterol metabolism by promoting cholesterol-to-bile acid conversion and cholesterol efflux in rats.

    PubMed

    Zhang, Min; Xie, Zongkai; Gao, Weina; Pu, Lingling; Wei, Jingyu; Guo, Changjiang

    2016-03-01

    Quercetin, a common member of the flavonoid family, is widely present in plant kingdom. Despite that quercetin is implicated in regulating cholesterol metabolism, the molecular mechanism is poorly understood. We hypothesized that quercetin regulates cholesterol homeostasis through regulating the key enzymes involved in hepatic cholesterol metabolism. To test this hypothesis, we compared the profile of key enzymes and transcription factors involved in the hepatic cholesterol metabolism in rats with or without quercetin supplementation. Twenty male Wistar rats were randomly divided into control and quercetin-supplemented groups. Serum total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and total bile acids in feces and bile were measured. Hepatic enzymatic activities were determined by activity assay kit and high-performance liquid chromatography-based analyses. The messenger RNA (mRNA) and protein expressions were determined by reverse transcriptase polymerase chain reaction and Western blot analyses, respectively. The results showed that the activity of hepatic cholesterol 7α-hydroxylase, a critical enzyme in the conversion of cholesterol to bile acids, was significantly elevated by quercetin. The expression of cholesterol 7α-hydroxylase, as well as liver X receptor α, an important transcription factor, was also increased at both mRNA and protein levels by quercetin. However, quercetin exposure had no impact on the activity of hepatic HMG-CoA reductase, a rate-limiting enzyme in the biosynthesis of cholesterol. We also found that quercetin treatment significantly increased ATP binding cassette transporter G1 mRNA and protein expression in the liver, suggesting that quercetin may increase hepatic cholesterol efflux. Collectively, the results presented here indicate that quercetin regulates hepatic cholesterol metabolism mainly through the pathways that promote cholesterol-to-bile acid conversion and

  20. The role of grain boundaries and transient porosity increase as fluid pathways for reaction front propagation

    NASA Astrophysics Data System (ADS)

    Jonas, Laura; John, Timm; Geisler, Thorsten; Putnis, Andrew

    2013-04-01

    The pseudomorphic replacement of Carrara marble by calcium phosphates was studied as a model system to examine the influence of different fluid pathways for reaction front propagation induced by fluid-rock interaction. In this model system, the grain boundaries present in the rock and the transient porosity structures developing throughout the replacement reaction enable the reaction front to progress further into the rock as well as to the center of each single grain until complete transformation. Hydrothermal treatment of the marble using phosphate bearing solutions at temperature levels of 150° C and 200° C for different durations lead to the formation of two product phases which were identified as hydroxyapatite [Ca5(PO4)3OH] as well as β-tricalcium phosphate [β-Ca3(PO4)2] (β-TCP). The formation of β-TCP was probably favored by the presence of ~0.6wt.% of Mg in the parent phase. Completely transformed single grains show a distinctive zoning, both in composition and texture. Whereas areas next to the grain boundary consist of nearly pure hydroxyapatite and show a coarse porosity, areas close to the center of the single grains show a high amount of β-TCP and a very fine porous microstructure. If F was added as an additional solution component, the formation of β-TCP was avoided and up to 3wt.% of F were incorporated into the product apatite. The use of the isotope 18O as a chronometer for the replacement reaction makes it possible to reconstruct the chronological development of the calcium phosphate reaction front. Raman analysis revealed that the incorporation of 18O in the PO4 tetrahedron of hydroxyapatite results in the development of distinct profiles in the calcium phosphate reaction front perpendicular to the grain boundaries of the marble. Through the use of the 18O chronometer, it is possible to estimate and compare the time effectiveness of the different fluid pathways in this model system. The results show that the grain boundaries serve as a

  1. Quercetin inhibits radiation-induced skin fibrosis.

    PubMed

    Horton, Jason A; Li, Fei; Chung, Eun Joo; Hudak, Kathryn; White, Ayla; Krausz, Kristopher; Gonzalez, Frank; Citrin, Deborah

    2013-08-01

    Radiation induced fibrosis of the skin is a late toxicity that may result in loss of function due to reduced range of motion and pain. The current study sought to determine if oral delivery of quercetin mitigates radiation-induced cutaneous injury. Female C3H/HeN mice were fed control chow or quercetin-formulated chow (1% by weight). The right hind leg was exposed to 35 Gy of X rays and the mice were followed serially to assess acute toxicity and hind leg extension. Tissue samples were collected for assessment of soluble collagen and tissue cytokines. Human and murine fibroblasts were subjected to clonogenic assays to determine the effects of quercetin on radiation response. Contractility of fibroblasts was assessed with a collagen contraction assay in the presence or absence of quercetin and transforming growth factor-β (TGF-β). Western blotting of proteins involved in fibroblast contractility and TGF-β signaling were performed. Quercetin treatment significantly reduced hind limb contracture, collagen accumulation and expression of TGF-β in irradiated skin. Quercetin had no effect on the radioresponse of fibroblasts or murine tumors, but was capable of reducing the contractility of fibroblasts in response to TGF-β, an effect that correlated with partial stabilization of phosphorylated cofilin. Quercetin is capable of mitigating radiation induced skin fibrosis and should be further explored as a therapy for radiation fibrosis.

  2. Quercetin-induced cardioprotection against doxorubicin cytotoxicity

    PubMed Central

    2013-01-01

    Background Cancer has continually been the leading cause of death worldwide for decades. Thus, scientists have actively devoted themselves to studying cancer therapeutics. Doxorubicin is an efficient drug used in cancer therapy, but also produces reactive oxygen species (ROS) that induce severe cytotoxicity against heart cells. Quercetin, a plant-derived flavonoid, has been proven to contain potent antioxidant and anti-inflammatory properties. Thus, this in vitro study investigated whether quercetin can decrease doxorubicin-induced cytotoxicity and promote cell repair systems in cardiomyocyte H9C2 cells. Results Proteomic analysis and a cell biology assay were performed to investigate the quercetin-induced responses. Our data demonstrated that quercetin treatment protects the cardiomyocytes in a doxorubicin-induced heart damage model. Quercetin significantly facilitated cell survival by inhibiting cell apoptosis and maintaining cell morphology by rearranging the cytoskeleton. Additionally, 2D-DIGE combined with MALDI-TOF MS analysis indicated that quercetin might stimulate cardiomyocytes to repair damage after treating doxorubicin by modulating metabolic activation, protein folding and cytoskeleton rearrangement. Conclusion Based on a review of the literature, this study is the first to report detailed protective mechanisms for the action of quercetin against doxorubicin-induced cardiomyocyte toxicity based on in-depth cell biology and proteomic analysis. PMID:24359494

  3. Quercetin Inhibits Radiation-Induced Skin Fibrosis

    PubMed Central

    Horton, Jason A.; Li, Fei; Chung, Eun Joo; Hudak, Kathryn; White, Ayla; Krausz, Kristopher; Gonzalez, Frank; Citrin, Deborah

    2013-01-01

    Radiation induced fibrosis of the skin is a late toxicity that may result in loss of function due to reduced range of motion and pain. The current study sought to determine if oral delivery of quercetin mitigates radiation-induced cutaneous injury. Female C3H/HeN mice were fed control chow or quercetin-formulated chow (1% by weight). The right hind leg was exposed to 35 Gy of X rays and the mice were followed serially to assess acute toxicity and hind leg extension. Tissue samples were collected for assessment of soluble collagen and tissue cytokines. Human and murine fibroblasts were subjected to clonogenic assays to determine the effects of quercetin on radiation response. Contractility of fibroblasts was assessed with a collagen contraction assay in the presence or absence of quercetin and transforming growth factor-β (TGF-β). Western blotting of proteins involved in fibroblast contractility and TGF-β signaling were performed. Quercetin treatment significantly reduced hind limb contracture, collagen accumulation and expression of TGF-β in irradiated skin. Quercetin had no effect on the radioresponse of fibroblasts or murine tumors, but was capable of reducing the contractility of fibroblasts in response to TGF-β, an effect that correlated with partial stabilization of phosphorylated cofilin. Quercetin is capable of mitigating radiation induced skin fibrosis and should be further explored as a therapy for radiation fibrosis. PMID:23819596

  4. Uptake of quercetin and quercetin 3-glucoside from whole onion and apple peel extracts by Caco-2 cell monolayers.

    PubMed

    Boyer, Jeanelle; Brown, Dan; Liu, Rui Hai

    2004-11-17

    Evidence suggests that regular consumption of fruits and vegetables may reduce the risk of chronic diseases, and phytochemicals from fruits and vegetables may be responsible for this health benefit. However, there is limited knowledge on the bioavailability of specific phytochemicals from whole fruits and vegetables. This study used Caco-2 cells to examine uptake of quercetin aglycon and quercetin 3-glucoside as purified compounds and from whole onion and apple peel extracts. Pure quercetin aglycon was absorbed by the Caco-2 cells in higher concentrations than quercetin 3-glucoside (p < 0.05). Caco-2 cells treated with quercetin 3-glucoside accumulated both quercetin 3-glucoside and quercetin. Caco-2 cells absorbed more onion quercetin aglycon than onion quercetin 3-glucoside (p < 0.05), and the percentage of onion quercetin absorbed was greater than that of pure quercetin, most likely due to enzymatic hydrolysis of quercetin 3-glucoside and other quercetin glucosides found in the onion by the Caco-2 cells. Caco-2 cells absorbed low levels of quercetin 3-glucoside from apple peel extracts, but quercetin aglycon absorption was not detected. Caco-2 cell homogenates demonstrated both lactase and glucosidase activities when incubated with lactose and quercetin 3-glucoside, respectively. This use of the Caco2 cell model appears to be a simple and useful system for studying bioavailability of whole food phytochemicals and may be used to assess differences in bioavailability between foods. PMID:15537334

  5. Uptake of quercetin and quercetin 3-glucoside from whole onion and apple peel extracts by Caco-2 cell monolayers.

    PubMed

    Boyer, Jeanelle; Brown, Dan; Liu, Rui Hai

    2004-11-17

    Evidence suggests that regular consumption of fruits and vegetables may reduce the risk of chronic diseases, and phytochemicals from fruits and vegetables may be responsible for this health benefit. However, there is limited knowledge on the bioavailability of specific phytochemicals from whole fruits and vegetables. This study used Caco-2 cells to examine uptake of quercetin aglycon and quercetin 3-glucoside as purified compounds and from whole onion and apple peel extracts. Pure quercetin aglycon was absorbed by the Caco-2 cells in higher concentrations than quercetin 3-glucoside (p < 0.05). Caco-2 cells treated with quercetin 3-glucoside accumulated both quercetin 3-glucoside and quercetin. Caco-2 cells absorbed more onion quercetin aglycon than onion quercetin 3-glucoside (p < 0.05), and the percentage of onion quercetin absorbed was greater than that of pure quercetin, most likely due to enzymatic hydrolysis of quercetin 3-glucoside and other quercetin glucosides found in the onion by the Caco-2 cells. Caco-2 cells absorbed low levels of quercetin 3-glucoside from apple peel extracts, but quercetin aglycon absorption was not detected. Caco-2 cell homogenates demonstrated both lactase and glucosidase activities when incubated with lactose and quercetin 3-glucoside, respectively. This use of the Caco2 cell model appears to be a simple and useful system for studying bioavailability of whole food phytochemicals and may be used to assess differences in bioavailability between foods.

  6. Transient increase in obese gene expression after food intake or insulin administration.

    PubMed

    Saladin, R; De Vos, P; Guerre-Millo, M; Leturque, A; Girard, J; Staels, B; Auwerx, J

    1995-10-12

    Obesity is a disorder of energy balance, indicating a chronic disequilibrium between energy intake and expenditure. Recently, the mouse ob gene, and subsequently its human and rat homologues, have been cloned. The ob gene product, leptin, is expressed exclusively in adipose tissue, and appears to be a signalling factor regulating body-weight homeostasis and energy balance. Because the level of ob gene expression might indicate the size of the adipose depot, we suggest that it is regulated by factors modulating adipose tissue size. Here we show that ob gene exhibits diurnal variation, increasing during the night, after rats start eating. This variation was linked to changes in food intake, as fasting prevented the cyclic variation and decreased ob messenger RNA. Furthermore, refeeding fasted rats restored ob mRNA within 4 hours to levels of fed animals. A single insulin injection in fasted animals increased ob mRNA to levels of fed controls. Experiments to control glucose and insulin independently in animals, and studies in primary adipocytes, showed that insulin regulates ob gene expression directly in rats, regardless of its glucose-lowering effects. Whereas the ob gene product, leptin, has been shown to reduce food intake and increase energy expenditure, our data demonstrate that ob gene expression is increased after food ingestion in rats, perhaps through a direct action of insulin on the adipocyte.

  7. A Temporal-Specific and Transient cAMP Increase Characterizes Odorant Classical Conditioning

    ERIC Educational Resources Information Center

    Cui, Wen; Smith, Andrew; Darby-King, Andrea; Harley, Carolyn W.; McLean, John H.

    2007-01-01

    Increases in cyclic adenosine monophosphate (cAMP) are proposed to initiate learning in a wide variety of species. Here, we measure changes in cAMP in the olfactory bulb prior to, during, and following a classically conditioned odor preference trial in rat pups. Measurements were taken up to the point of maximal CREB phosphorylation in olfactory…

  8. Quercetin Induces Hepatic Lipid Omega-Oxidation and Lowers Serum Lipid Levels in Mice

    PubMed Central

    Hoek-van den Hil, Elise F.; Keijer, Jaap; Bunschoten, Annelies; Vervoort, Jacques J. M.; Stankova, Barbora; Bekkenkamp, Melissa; Herreman, Laure; Venema, Dini; Hollman, Peter C. H.; Tvrzicka, Eva; Rietjens, Ivonne M. C. M.; van Schothorst, Evert M.

    2013-01-01

    Elevated circulating lipid levels are known risk factors for cardiovascular diseases (CVD). In order to examine the effects of quercetin on lipid metabolism, mice received a mild-high-fat diet without (control) or with supplementation of 0.33% (w/w) quercetin for 12 weeks. Gas chromatography and 1H nuclear magnetic resonance were used to quantitatively measure serum lipid profiles. Whole genome microarray analysis of liver tissue was used to identify possible mechanisms underlying altered circulating lipid levels. Body weight, energy intake and hepatic lipid accumulation did not differ significantly between the quercetin and the control group. In serum of quercetin-fed mice, triglycerides (TG) were decreased with 14% (p<0.001) and total poly unsaturated fatty acids (PUFA) were increased with 13% (p<0.01). Palmitic acid, oleic acid, and linoleic acid were all decreased by 9–15% (p<0.05) in quercetin-fed mice. Both palmitic acid and oleic acid can be oxidized by omega (ω)-oxidation. Gene expression profiling showed that quercetin increased hepatic lipid metabolism, especially ω-oxidation. At the gene level, this was reflected by the up-regulation of cytochrome P450 (Cyp) 4a10, Cyp4a14, Cyp4a31 and Acyl-CoA thioesterase 3 (Acot3). Two relevant regulators, cytochrome P450 oxidoreductase (Por, rate limiting for cytochrome P450s) and the transcription factor constitutive androstane receptor (Car; official symbol Nr1i3) were also up-regulated in the quercetin-fed mice. We conclude that quercetin intake increased hepatic lipid ω-oxidation and lowered corresponding circulating lipid levels, which may contribute to potential beneficial effects on CVD. PMID:23359794

  9. Beneficial effects of quercetin on renal injury and oxidative stress caused by ciprofloxacin in rats: A histological and biochemical study.

    PubMed

    Elbe, H; Dogan, Z; Taslidere, E; Cetin, A; Turkoz, Y

    2016-03-01

    Ciprofloxacin is a broad-spectrum quinolone antibiotic commonly used in clinical practice. Quercetin is an antioxidant belongs to flavonoid group. It inhibits the production of superoxide anion. In this study, we aimed to evaluate the effects of quercetin on renal injury and oxidative stress caused by ciprofloxacin. Twenty-eight female Wistar albino rats were divided into four groups: control, quercetin (20 mg kg(-1) day(-1) gavage for 21 days), ciprofloxacin (20 mg kg(-1) twice a day intraperitoneally for 10 days), and ciprofloxacin + quercetin. Samples were processed for histological and biochemical evaluations. Malondialdehyde (MDA) and glutathione (GSH) levels, superoxide dismutase (SOD), and catalase (CAT) activities were measured in kidney tissue. The ciprofloxacin group showed histopathological changes such as infiltration, dilatation in tubules, tubular atrophy, reduction of Bowman's space, congestion, hemorrhage, and necrosis. In the ciprofloxacin + quercetin group, these histopathological changes markedly reduced. MDA levels increased in the ciprofloxacin group and decreased in the ciptofloxacin + quercetin group. SOD and CAT activities and GSH levels significantly decreased in the ciprofloxacin group. On the other hand, in the ciprofloxacin + quercetin group, SOD and CAT activities and GSH levels significantly increased with regard to the ciprofloxacin group. We concluded that quercetin has antioxidative and therapeutic effects on renal injury and oxidative stress caused by ciprofloxacin in rats.

  10. Role of quercetin as an alternative for obesity treatment: you are what you eat!

    PubMed

    Nabavi, Seyed Fazel; Russo, Gian Luigi; Daglia, Maria; Nabavi, Seyed Mohammad

    2015-07-15

    Obesity is one of the most serious global health problems, which increases the risk of other different chronic diseases. The crucial role of oxidative stress in the initiation and progression of obesity leads to the hypothesis that antioxidants can be used as therapeutic agents for obesity treatment. Among antioxidants, much attention has been paid to polyphenols due to their negligible adverse effects. Among them, quercetin is one of the most common dietary antioxidants widely distributed in different plant materials, such as fruits, vegetables and cereals. Quercetin shows a wide range of biological and health-promoting effects, such as anticancer, hepatoprotective, antidiabetic, anti-inflammatory and antibacterial activities. Furthermore, quercetin has anti-obesity activity through mitogen-activated protein kinase and adenine monophosphate-activated protein kinase signaling pathways. In this study, we reviewed the available scientific reports concerning the beneficial role of quercetin against obesity with emphasis on its mechanisms of action.

  11. 3-Iodothyronamine increases transient receptor potential melastatin channel 8 (TRPM8) activity in immortalized human corneal epithelial cells.

    PubMed

    Lucius, Alexander; Khajavi, Noushafarin; Reinach, Peter S; Köhrle, Josef; Dhandapani, Priyavathi; Huimann, Philipp; Ljubojevic, Nina; Grötzinger, Carsten; Mergler, Stefan

    2016-03-01

    3-Iodothyronamine (3T1AM) is an endogenous thyroid hormone metabolite that interacts with the human trace amine-associated receptor 1 (hTAAR1), a G-protein-coupled receptor, to induce numerous physiological responses including dose-dependent body temperature lowering in rodents. 3T1AM also directly activates cold-sensitive transient receptor potential melastatin 8 (TRPM8) channels in human conjunctival epithelial cells (HCjEC) at constant temperature as well as reducing rises in IL-6 release induced by transient receptor potential vanilloid 1 (TRPV1) activation by capsaicin (CAP). Here, we describe that 3T1AM-induced TRPM8 activation suppresses through crosstalk TRPV1 activation in immortalized human corneal epithelial cells (HCEC). RT-PCR and immunofluorescent staining identified TRPM8 gene and protein expression. Increases in Ca(2+) influx induced by the TRPM8 agonists either 3T1AM (0.1-10 μM), menthol (500 μM), icilin (15-60 μM) or temperature lowering (either <17°C or >17°C) were all blocked by 10-20 μM BCTC, a mixed TRPV1/TRPM8 antagonist. BCTC blocked 3T1AM-induced recombinant TRPM8 activation of Ca(2+) transients in an osteosarcoma heterologous expression system. The effects of BCTC in HCEC were attributable to selective TRPM8 inhibition since whole-cell patch-clamp currents underlying Ca(2+) rises induced by 20 μM CAP were BCTC insensitive. On the other hand, Ca(2+) transients induced by activating TRPV1 with either CAP or a hyperosmolar medium were suppressed during exposure to either 1 μM 3T1AM or 15 μM icilin. All of these modulatory effects on intracellular Ca(2+) regulation induced by the aforementioned agents were attributable to changes in underlying inward and outward current. Taken together, TRPM8 activation by 3T1AM markedly attenuates and even eliminates hyperosmolar and CAP induced TRPV1 activation through crosstalk.

  12. Transient responses of the CSIRO climate model to two different rates of CO2 increase

    NASA Astrophysics Data System (ADS)

    Cai, W.; Gordon, H. B.

    The responses of the CSIRO coupled atmosphere-ocean-sea ice model to two greenhouse gas induced warming scenarios are described and compared to a control run with the current CO2 level. In one scenario, denoted IS92a, the atmospheric CO2 increases such that it reaches doubling after 128 years. In the other, the CO2 increases at 1% per year compounding (doubling after 70 y). As the CO2 increases in both scenarios, the top-of-atmosphere outgoing longwave radiation increases giving enhanced cooling of the coupled system, while the outgoing short wave radiation decreases contributing to a warming of the system. The latter overcompensates the former leading to a global mean net radiative heat gain. The distribution of this heat gain produces the well-known interhemispheric asymmetry in warming, despite a decrease in the sea ice around Antarctica in this model. It is found that the volume mean temperature response over the southern ocean is greater than that over the northern hemispheric oceans, and a maximum warming takes place at the subsurface rather at the surface of the ocean in the southern mid-to-high latitude region. The enhanced high-latitude freshening associated with the strengthened hydrological cycle significantly affects the latitudinal distribution of warming and other responses. It enhances the warming immediately equatorward of the deep water formation regions while produces a reduced warming, even a cooling, in these regions. In both runs, there is a decrease in the large-scale oceanic currents which have a significant thermohaline-driven component. The reduction in these currents reduces the poleward transport of salt out of the tropical and subtropical regions of these oceans. This and the enhanced evaporation contribute to considerable increases in surface salinity in the tropical and subtropical regions. In IS92a, the warming rate before doubling is smaller than that in 1% scenario, but the cumulative effects of the two experiments at the time of

  13. Transient increase in interleukin-8 and pulmonary microvascular permeability following aortic surgery.

    PubMed

    Raijmakers, P G; Groeneveld, A B; Rauwerda, J A; Schneider, A J; Teule, G J; Hack, C E; Thijs, L G

    1995-03-01

    Aortic surgery results in ischemia/reperfusion of the lower body. This may liberate inflammatory mediators that activate neutrophils, and may result in lung microvascular changes with increased permeability and respiratory failure. We studied circulating inflammatory mediators and the pulmonary leak index (PLI) of 67Ga, a measure of transvascular transferrin transport and permeability, in patients scheduled for elective aortic and peripheral vascular surgery, before and after surgery. Aortic surgery patients in Groups 1 (n = 10) and 2 (n = 7) were studied before and at a median of 2.5 and 21.0 h after surgery, respectively. A control Group 3 (n = 6) was studied before and at a median of 2.9 h after peripheral vascular surgery. The PLI (median) increased from a median of 9.1 (range, 6.6 to 14.7) before to a median of 23.4 (range, 18.7 to 86.4) x 10(-3)/min after surgery in Group 1 but not in the other groups (p < 0.001). The postoperative increase in circulating neutrophils and elastase-alpha 1-antitrypsin, a marker of neutrophil activation, was similar among the groups. Plasma levels of activated complement 3a and tumor necrosis factor (TNF-alpha) did not change in any of the groups. In contrast, plasma levels of interleukin-8 (IL-8) increased in Group 1 from < 3 (range, < 3 to 37) before to 324 (range, 36 to 868) pg/ml after surgery, but did not change in the other groups (p < 0.005). The decrease in plasma levels of angiotensin converting enzyme (ACE) was greater in Group 1 than in the other groups (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

  14. Ductile creep and compaction: A mechanism for transiently increasing fluid pressure in mostly sealed fault zones

    USGS Publications Warehouse

    Sleep, N.H.; Blanpied, M.L.

    1994-01-01

    A simple cyclic process is proposed to explain why major strike-slip fault zones, including the San Andreas, are weak. Field and laboratory studies suggest that the fluid within fault zones is often mostly sealed from that in the surrounding country rock. Ductile creep driven by the difference between fluid pressure and lithostatic pressure within a fault zone leads to compaction that increases fluid pressure. The increased fluid pressure allows frictional failure in earthquakes at shear tractions far below those required when fluid pressure is hydrostatic. The frictional slip associated with earthquakes creates porosity in the fault zone. The cycle adjusts so that no net porosity is created (if the fault zone remains constant width). The fluid pressure within the fault zone reaches long-term dynamic equilibrium with the (hydrostatic) pressure in the country rock. One-dimensional models of this process lead to repeatable and predictable earthquake cycles. However, even modest complexity, such as two parallel fault splays with different pressure histories, will lead to complicated earthquake cycles. Two-dimensional calculations allowed computation of stress and fluid pressure as a function of depth but had complicated behavior with the unacceptable feature that numerical nodes failed one at a time rather than in large earthquakes. A possible way to remove this unphysical feature from the models would be to include a failure law in which the coefficient of friction increases at first with frictional slip, stabilizing the fault, and then decreases with further slip, destabilizing it. ?? 1994 Birkha??user Verlag.

  15. Activation of muscarinic receptors in porcine airway smooth muscle elicits a transient increase in phospholipase D activity.

    PubMed

    Mamoon, A M; Smith, J; Baker, R C; Farley, J M

    1999-01-01

    Phospholipase D (PLD) is a phosphodiesterase that catalyses hydrolysis of phosphatidylcholine to produce phosphatidic acid and choline. In the presence of ethanol, PLD also catalyses the formation of phosphatidylethanol, which is a unique characteristic of this enzyme. Muscarinic receptor-induced changes in the activity of PLD were investigated in porcine tracheal smooth muscle by measuring the formation of [3H]phosphatidic acid ([3H]PA) and [3H]phosphatidylethanol ([3H]PEth) after labeling the muscle strips with [3H]palmitic acid. The cholinergic receptor agonist acetylcholine (Ach) significantly but transiently increased formation of both [3H]PA and [3H]PEth in a concentration-dependent manner (>105-400% vs. controls in the presence of 10(-6) to 10(-4) M Ach) when pretreated with 100 mM ethanol. The Ach receptor-mediated increase in PLD activity was inhibited by atropine (10(-6) M), indicating that activation of PLD occurred via muscarinic receptors. Activation of protein kinase C (PKC) by phorbol-12-myristate-13-acetate (PMA) increased PLD activity that was effectively blocked by the PKC inhibitors calphostin C (10(-8) to 10(-6) M) and GFX (10(-8) to 10(-6) M). Ach-induced increases in PLD activity were also significantly, but incompletely, inhibited by both GFX and calphostin C. From the present data, we conclude that in tracheal smooth muscle, muscarinic acetylcholine receptor-induced PLD activation is transient in nature and coupled to these receptors via PKC. However, PKC activation is not solely responsible for Ach-induced activation of PLD in porcine tracheal smooth muscle.

  16. Delay-Induced Transient Increase and Heterogeneity in Gene Expression in Negatively Auto-Regulated Gene Circuits

    PubMed Central

    Maithreye, R.; Sarkar, Ram Rup; Parnaik, Veena K.; Sinha, Somdatta

    2008-01-01

    A generic feature in all intracellular biochemical processes is the time required to complete the whole sequence of reactions to yield any observable quantity-from gene expression to circadian rhythms. This widespread phenomenon points towards the importance of time delay in biological functions. Theoretically time delay is known to be the source of instability, and has been attributed to lead to oscillations or transient dynamics in several biological functions. Negative feedback loops, common in biochemical pathways, have been shown to provide stability and withstand considerable variations and random perturbations of biochemical parameters. The interaction of these two opposing factors-of instability and homeostasis-are features that are widespread in intracellular processes. To test the effect of these divergent forces in the dynamics of gene expression, we have designed and constructed simple negatively auto-regulated gene circuits consisting of a basic regulator and transcriptional repressor module, and compared it with one, which has delayed repression. We show, both theoretically and experimentally, that delayed repression induces transient increase and heterogeneity in gene expression before the gain of stability effected by the negative feedback. This design, therefore, seems to be suitable for conferring both stability and variability in cells required for adaptive response to a noisy environment. PMID:18698420

  17. Transient increase in phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol trisphosphate during activation of human neutrophils.

    PubMed

    Traynor-Kaplan, A E; Thompson, B L; Harris, A L; Taylor, P; Omann, G M; Sklar, L A

    1989-09-15

    We recently showed that phosphatidylinositol trisphosphate (PIP3) was present in a unique lipid fraction generated in neutrophils during activation. Here, we demonstrate that the band containing this fraction isolated from thin layer chromatography consists primarily of PIP3 and that only small amounts of radiolabeled PIP3 exist prior to activation. In addition, high performance liquid chromatography of deacylated phospholipids from stimulated cells reveals an increase in a fraction eluting ahead of glycerophosphoinositol 4,5-P2. After removal of the glycerol we found that it coeluted with inositol 1,3,4-P3 when resubjected to high performance liquid chromatography. Thus, we have detected a second, novel form of phosphatidylinositol bisphosphate in activated neutrophils, PI-(3,4)P2. The elevation of PIP3 through the formyl peptide receptor is blocked by pretreatment with pertussis toxin, implicating mediation of the increase in PIP3 by a guanosine triphosphate-binding (G) protein. The rise in PIP3 is not secondary to calcium elevation. Buffering the rise in intracellular calcium did not diminish the increase in PIP3. The elevation of PIP3 appears to occur during activation with physiological agonists, its level varying with the degree of activation. Leukotriene B4, which elicits many of the same responses as stimulation of the formyl peptide receptor but with minimal oxidant production, stimulates a much attenuated rise in PIP3. Isoproterenol, which inhibits oxidant production also reduces the rise in PIP3. Hence formation of PI(3,4)P2 and PIP3 (presumed to be PI(3,4,5)P3) correlates closely with the early events of neutrophil activation. PMID:2549071

  18. Synthesis and antiviral activity of substituted quercetins.

    PubMed

    Thapa, Mahendra; Kim, Yunjeong; Desper, John; Chang, Kyeong-Ok; Hua, Duy H

    2012-01-01

    Influenza viruses are important pathogens that cause respiratory infections in humans and animals. In addition to vaccination, antiviral drugs against influenza virus play a significant role in controlling viral infections by reducing disease progression and virus transmission. Plant derived polyphenols are associated with antioxidant activity, anti-carcinogenic, and cardio- and neuro-protective actions. Some polyphenols, such as resveratrol and epigallocatechin gallate (EGCG), showed significant anti-influenza activity in vitro and/or in vivo. Recently we showed that quercetin and isoquercetin (quercetin-3-β-d-glucoside), a glucoside form of quercetin, significantly reduced the replication of influenza viruses in vitro and in vivo (isoquercetin). The antiviral effects of isoquercetin were greater than that of quercetin with lower IC(50) values and higher in vitro therapeutic index. Thus, we investigated the synthesis and antiviral activities of various quercetin derivatives with substitution of C3, C3', and C5 hydroxyl functions with various phenolic ester, alkoxy, and aminoalkoxy moieties. Among newly synthesized compounds, quercetin-3-gallate which is structurally related to EGCG showed comparable antiviral activity against influenza virus (porcine H1N1 strain) to that of EGCG with improved in vitro therapeutic index.

  19. Transient Increase in Homocysteine but Not Hyperhomocysteinemia during Acute Exercise at Different Intensities in Sedentary Individuals

    PubMed Central

    Iglesias-Gutiérrez, Eduardo; Egan, Brendan; Díaz-Martínez, Ángel Enrique; Peñalvo, José Luis; González-Medina, Antonio; Martínez-Camblor, Pablo; O’Gorman, Donal J.; Úbeda, Natalia

    2012-01-01

    Considering that hyperhomocysteinemia is an independent risk factor for cardiovascular disease, the purpose of this study was to determine the kinetics of serum homocysteine (tHcy) and the vitamins involved in its metabolism (folates, B12, and B6) in response to acute exercise at different intensities. Eight sedentary males (18–27 yr) took part in the study. Subjects were required to complete two isocaloric (400 kcal) acute exercise trials on separate occasions at 40% (low intensity, LI) and 80% VO2peak (high intensity, HI). Blood samples were drawn at different points before (pre4 and pre0 h), during (exer10, exer20, exer30, exer45, and exer60 min), and after exercise (post0, post3, and post19 h). Dietary, genetic, and lifestyle factors were controlled. Maximum tHcy occurred during exercise, both at LI (8.6 (8.0–10.1) µmol/L, 9.3% increase from pre0) and HI (9.4 (8.2–10.6) µmol/L, 25.7% increase from pre0), coinciding with an accumulated energy expenditure independent of the exercise intensity. From this point onwards tHcy declined until the cessation of exercise and continued descending. At post19, tHcy was not different from pre-exercise values. No values of hyperhomocysteinemia were observed at any sampling point and intensity. In conclusion, acute exercise in sedentary individuals, even at HI, shows no negative effect on tHcy when at least 400 kcal are spent during exercise and the nutritional status for folate, B12, and B6 is adequate, since no hyperhomocysteinemia has been observed and basal concentrations were recovered in less than 24 h. This could be relevant for further informing healthy exercise recommendations. PMID:23236449

  20. Jasmonic acid transient accumulation is needed for abscisic acid increase in citrus roots under drought stress conditions.

    PubMed

    de Ollas, Carlos; Hernando, Bárbara; Arbona, Vicent; Gómez-Cadenas, Aurelio

    2013-03-01

    Phytohormones are central players in sensing and signaling numerous environmental conditions like drought stress. In this work, an experimental system based on severe drought was established and hormone profiling together with gene expression of key enzymes involved in abscisic acid (ABA) and jasmonic acid (JA) biosynthesis was studied in roots of citrumelo CPB 4475 (a commercial citrus rootstock) plants. JA concentration transiently increased after a few hours of stress, returning to control levels 30 h after the onset of the condition. A more progressive ABA accumulation was observed, with the onset of this increase at the same time or right after the JA transient accumulation. Molecular data suggested that, at least, part of the hormonal regulation takes place at the biosynthetic level. These observations also pointed to a possible involvement of JA on ABA biosynthesis under stress. To test this hypothesis, JA and ABA biosynthesis were chemically inhibited and subsequently phenotypes rescued by the addition of exogenous hormones. Results showed that the early JA accumulation was necessary for the subsequent ABA increase in roots under stress whereas the opposite could not be stated. The model includes a burst of JA in roots of citrus under severe drought stress conditions that leads to a more progressive ABA accumulation that will induce later plant responses. The present work adds a new level of interaction between JA and ABA at the biosynthetic level that together with the previously described interaction between signal transduction cascades of the two hormones would allow plants to fine-tune specific responses to different stimuli.

  1. Quercetin inhibits inflammatory bone resorption in a mouse periodontitis model.

    PubMed

    Napimoga, Marcelo H; Clemente-Napimoga, Juliana T; Macedo, Cristina G; Freitas, Fabiana F; Stipp, Rafael N; Pinho-Ribeiro, Felipe A; Casagrande, Rubia; Verri, Waldiceu A

    2013-12-27

    Periodontitis is a disease that leads to bone destruction and represents the main cause of tooth loss in adults. The development of aggressive periodontitis has been associated with increased inflammatory response that is induced by the presence of a subgingival biofilm containing Aggregatibacter actinomycetemcomitans. The flavonoid quercetin (1) is widespread in vegetables and fruits and exhibits many biological properties for possible medical and clinical applications such as its anti-inflamatory and antioxidant effects. Thus, in the present study, the properties of 1 have been evaluated in bone loss and inflammation using a mouse periodontitis model induced by A. actinomycetemcomitans infection. Subcutaneous treatment with 1 reduced A. actinomycetemcomitans-induced bone loss and IL-1β, TNF-α, IL-17, RANKL, and ICAM-1 production in the gingival tissue without affecting bacterial counts. These results demonstrated that quercetin exhibits protective effects in A. actinomycetemcomitans-induced periodontitis in mice by modulating cytokine and ICAM-1 production.

  2. Striatal Injury with 6-OHDA Transiently Increases Cerebrospinal GFAP and S100B

    PubMed Central

    Batassini, Cristiane; Broetto, Núbia; Tortorelli, Lucas Silva; Borsoi, Milene; Zanotto, Caroline; Galland, Fabiana; Souza, Tadeu Mello; Leite, Marina Concli; Gonçalves, Carlos-Alberto

    2015-01-01

    Both glial fibrillary acidic protein (GFAP) and S100B have been used as markers of astroglial plasticity, particularly in brain injury; however, they do not necessarily change in the same time frame or direction. Herein, we induced a Parkinson's disease (PD) model via a 6-OHDA intrastriatal injection in rats and investigated the changes in GFAP and S100B using ELISA in the substantia nigra (SN), striatum, and cerebrospinal fluid on the 1st, 7th, and 21st days following the injection. The model was validated using measurements of rotational behaviour induced by methylphenidate and tyrosine hydroxylase in the dopaminergic pathway. To our knowledge, this is the first measurement of cerebrospinal fluid S100B and GFAP in the 6-OHDA model of PD. Gliosis (based on a GFAP increase) was identified in the striatum, but not in the SN. We identified a transitory increment of cerebrospinal fluid S100B and GFAP on the 1st and 7th days, respectively. This initial change in cerebrospinal fluid S100B was apparently related to the mechanical lesion. However, the 6-OHDA-induced S100B secretion was confirmed in astrocyte cultures. Current data reinforce the idea that glial changes precede neuronal damage in PD; however, these findings also indicate that caution is necessary regarding the interpretation of data in this PD model. PMID:26090233

  3. Osteoblast-specific overexpression of amphiregulin leads to transient increase in femoral cancellous bone mass in mice.

    PubMed

    Vaidya, Mithila; Lehner, Diana; Handschuh, Stephan; Jay, Freya F; Erben, Reinhold G; Schneider, Marlon R

    2015-12-01

    The epidermal growth factor receptor ligand amphiregulin (AREG) has been implicated in bone physiology and in bone anabolism mediated by intermittent parathyroid hormone treatment. However, the functions of AREG in bone have been only incipiently evaluated in vivo. Here, we generated transgenic mice overexpressing AREG specifically in osteoblasts (Col1-Areg). pQCT analysis of the femoral metaphysis revealed increased trabecular bone mass at 4, 8, and 10weeks of age in Col1-Areg mice compared to control littermates. However, the high bone mass phenotype was transient and disappeared in older animals. Micro-CT analysis of the secondary spongiosa confirmed increased trabecular bone volume and trabecular number in the distal femur of 4-week-old AREG-tg mice compared to control littermates. Furthermore, μ-CT analysis of the primary spongiosa revealed unaltered production of new bone trabeculae in distal femora of Col1-Areg mice. Histomorphometric analysis revealed a reduced number of osteoclasts in 4-week-old Col1-Areg mice, but not at later time points. Cancellous bone formation rate remained unchanged in Col1-Areg mice at all time points. In addition, bone mass and bone turnover in lumbar vertebral bodies were similar in Col1-Areg and control mice at all ages examined. Proliferation and differentiation of osteoblasts isolated from neonatal calvariae did not differ between Col1-Areg and control mice. Taken together, these data suggest that AREG overexpression in osteoblasts induces a transient high bone mass phenotype in the trabecular compartment of the appendicular skeleton by a growth-related, non-cell autonomous mechanism, leading to a positive bone balance with unchanged bone formation and lowered bone resorption.

  4. Endoscopic thyroidectomy along with bilateral central neck dissection (ETBC) increases the risk of transient hypoparathyroidism for patients with thyroid carcinoma.

    PubMed

    Xiang, Dapeng; Xie, Liangqi; Li, Zhiyu; Wang, Ping; Ye, Mao; Zhu, Mingzhu

    2016-09-01

    Increasing number of patients with thyroid carcinoma, especially young female patients, prefer to choose endoscopic thyroidectomy with bilateral central neck dissection (ETBC) for perfect cosmetic effects. However, the incidence of hypoparathyroidism after ETBC has not been well studied. Ninety six patients with papillary thyroid carcinoma were enrolled. All patients, including 49 ETBC and 47 open surgery patients, underwent total thyroidectomy with bilateral central neck dissection (CND). Some patients also underwent lateral neck dissection simultaneously. The incidence of hypoparathyroidism and parathyroid hormone (PTH) level were examined. Patients in the open surgery group had more advanced lesions, with larger tumor (p = 0.000), older age (p = 0.000), and more serious local involvement. The dissection extent of the open group was significantly larger than that of the ETBC group (p = 0.006). In contrast, the ETBC group with less dissection extent showed a significantly higher incidence of transient hypoparathyroidism than the open group (59.2 vs. 29.6 %, p = 0.004). The average PTH decline of the ETBC group was significantly higher than that of the open group on postoperative day 1 (POD1) (32.1 vs. 21.6 pg/ml, p = 0.010). Furthermore, the ETBC group had a significantly higher portion of patients with a PTH <10 pg/ml on POD1 (p = 0.001). One patient in the ETBC group developed permanent hypoparathyroidism. Autotransplantation and inadvertent removal rates of parathyroid did not differ between the two groups. Although generally considered a safe method for patients with thyroid carcinoma, ETBC may increase the risk of transient hypoparathyroidism compared with conventional open surgery.

  5. Quercetin, E7 and p53 in papillomavirus oncogenic cell transformation.

    PubMed

    Beniston, R G; Morgan, I M; O'Brien, V; Campo, M S

    2001-07-01

    Bovine papillomavirus type 4 (BPV-4) infects the upper alimentary canal of cattle causing benign papillomas which can progress to squamous carcinomas in cattle grazing on bracken fern (BF). We have previously shown that quercetin, a well characterized and potent mutagen found in BF, causes cell cycle arrest of primary bovine cells (PalF), but that a single exposure to quercetin can cause full oncogenic transformation of PalF cells partially transformed by BPV-4. Here we show that cell cycle arrest correlates with an increase in p53 protein levels and transcriptional activity. However, in cells transformed but non-tumorigenic, p53 protein is elevated and transcriptionally activated in response to quercetin or other DNA damaging stimuli, but the cells bypass quercetin-induced G1 arrest likely due to E7 expression. In transformed tumorigenic cells, p53 is elevated in response to quercetin but its transcriptional activity is inhibited due to mutation, and the cells fail to stop in G1 in the presence of quercetin.

  6. Onion extract and quercetin induce matrix metalloproteinase-1 in vitro and in vivo.

    PubMed

    Cho, Jae-We; Cho, Sun-Young; Lee, Seong-Ryong; Lee, Kyu-Suk

    2010-03-01

    A scar is usually developed by an imbalance of collagen synthesis and degradation. It is believed that the flavonoids (quercetin and kaempferol) in onion extract play a role in reducing scar formation through inhibition of fibroblast activities. Even though several commercial products are composed of onion extract, the precise molecular mechanisms of onion extract in reduction of scar formation in skin are still largely unknown. In this study we investigated the effect both of onion extract and quercetin on the proliferation of fibroblasts, expression of type I collagen and matrix metalloproteinase-1 (MMP-1). Our data show that proliferation rates of fibroblasts were decreased in a dose-dependent manner of the onion extract and quercetin. The expression of type I collagen was not markedly changed by the onion extract and quercetin. Interestingly, the expression of MMP-1 was markedly increased by both onion extract and quercetin in vitro and in vivo. Thus, our data indicate that onion extract and quercetin play a role in the anti-scar effect in skin through up-regulation of MMP-1 expression, implying this agent is a promising material for reducing scar formation.

  7. Protective Effects of Quercetin against Dimethoate-Induced Cytotoxicity and Genotoxicity in Allium sativum Test

    PubMed Central

    Ahmad, Waseem; Shaikh, Sibhghatulla; Nazam, Nazia; Lone, Mohammad Iqbal

    2014-01-01

    The present investigation was directed to study the possible protective activity of quercetin—a natural antioxidant against dimethoate-induced cyto- and genotoxicity in meristematic cells of Allium sativum. So far there is no report on the biological properties of quercetin in plant test systems. Chromosome breaks, multipolar anaphase, stick chromosome, and mitotic activity were undertaken in the current study as markers of cyto- and genotoxicity. Untreated control, quercetin controls (@ 5, 10 and 20 μg/mL for 3 h), and dimethoate exposed groups (@ 100 and 200 μg/mL for 3 h) were maintained. For protection against cytogenotoxicity, the root tip cells treated with dimethoate at 100 and 200 μg/mL for 3 h and quercetin treatment at 5, 10, and 20 μg/mL for 16 h, prior to dimethoate treatment, were undertaken. Quercetin was found to be neither cytotoxic nor genotoxic in Allium sativum control at these doses. A significant increase (P < 0.05) in chromosomal aberrations was noted in dimethoate treated Allium. Pretreatment of Allium sativum with quercetin significantly (P < 0.05) reduced dimethoate-induced genotoxicity and cytotoxicity in meristematic cells, and these effects were dose dependent. In conclusion, quercetin has a protective role in the abatement of dimethoate-induced cyto- and genotoxicity in the meristematic cells of Allium sativum that resides, at least in part, on its antioxidant effects. PMID:27379342

  8. Quercetin alleviates inflammation after short-term treatment in high-fat-fed mice.

    PubMed

    Das, Nilanjan; Sikder, Kunal; Bhattacharjee, Surajit; Majumdar, Suchandra Bhattacharya; Ghosh, Santinath; Majumdar, Subrata; Dey, Sanjit

    2013-06-01

    Consumption of a high-fat diet (HFD) promotes reactive oxygen species (ROS) which ultimately trigger inflammation. The aim of this study was to investigate the role of Moringa oleifera leaf extract (MoLE) and its active component quercetin in preventing NF-κB-mediated inflammation raised by short-term HFD. Quercetin was found to be one of the major flavonoid components from HPLC of MoLE. Swiss mice were fed for 15 days on HFD, both with or without MoLE/quercetin. The antioxidant profile was estimated from liver homogenate. NF-κB and some relevant inflammatory markers were evaluated by immunoblotting, RT-PCR and ELISA. Significantly (P < 0.05) lower antioxidant profile and higher lipid peroxidation was found in HFD group compared to control (P < 0.05). Increased nuclear import of NF-κB and elevated expressions of pro-inflammatory markers were further manifestations in the HFD group. All these changes were reversed in the MoLE/quercetin-treated groups with significant improvement of antioxidant activity compared to the HFD group. MoLE was found to be rich in polyphenols and both MoLE and quercetin showed potent free radical and hydroxyl radical quenching activity. Thus, the present study concluded that short-term treatment with MoLE and its constituent quercetin prevent HFD-mediated inflammation in mice. PMID:23644882

  9. Quercetin alleviates inflammation after short-term treatment in high-fat-fed mice.

    PubMed

    Das, Nilanjan; Sikder, Kunal; Bhattacharjee, Surajit; Majumdar, Suchandra Bhattacharya; Ghosh, Santinath; Majumdar, Subrata; Dey, Sanjit

    2013-06-01

    Consumption of a high-fat diet (HFD) promotes reactive oxygen species (ROS) which ultimately trigger inflammation. The aim of this study was to investigate the role of Moringa oleifera leaf extract (MoLE) and its active component quercetin in preventing NF-κB-mediated inflammation raised by short-term HFD. Quercetin was found to be one of the major flavonoid components from HPLC of MoLE. Swiss mice were fed for 15 days on HFD, both with or without MoLE/quercetin. The antioxidant profile was estimated from liver homogenate. NF-κB and some relevant inflammatory markers were evaluated by immunoblotting, RT-PCR and ELISA. Significantly (P < 0.05) lower antioxidant profile and higher lipid peroxidation was found in HFD group compared to control (P < 0.05). Increased nuclear import of NF-κB and elevated expressions of pro-inflammatory markers were further manifestations in the HFD group. All these changes were reversed in the MoLE/quercetin-treated groups with significant improvement of antioxidant activity compared to the HFD group. MoLE was found to be rich in polyphenols and both MoLE and quercetin showed potent free radical and hydroxyl radical quenching activity. Thus, the present study concluded that short-term treatment with MoLE and its constituent quercetin prevent HFD-mediated inflammation in mice.

  10. Quercetin may suppress rat aberrant crypt foci formation by suppressing inflammatory mediators that influence proliferation and apoptosis.

    PubMed

    Warren, Cynthia A; Paulhill, Kimberly J; Davidson, Laurie A; Lupton, Joanne R; Taddeo, Stella S; Hong, Mee Young; Carroll, Raymond J; Chapkin, Robert S; Turner, Nancy D

    2009-01-01

    The flavonoid quercetin suppresses cell proliferation and enhances apoptosis in vitro. In this study, we determined whether quercetin protects against colon cancer by regulating the protein level of phosphatidylinositol 3-kinase (PI 3-kinase) and Akt or by suppressing the expression of proinflammatory mediators [cyclooxygenase (COX)-1, COX-2, inducible nitric oxide synthase (iNOS)] during the aberrant crypt (AC) stage. Forty male rats were randomly assigned to receive diets containing quercetin (0 or 4.5 g/kg) and injected subcutaneously with saline or azoxymethane (AOM; 2 times during wk 3 and 4). The colon was resected 4 wk after the last AOM injection and samples were used to determine high multiplicity AC foci (HMACF; foci with >4 AC) number, colonocyte proliferation and apoptosis by immunohistochemistry, expression of PI 3-kinase (p85 and p85alpha subunits) and Akt by immunoblotting, and COX-1, COX-2, and iNOS expression by real time RT-PCR. Quercetin-fed rats had fewer (P = 0.033) HMACF. Relative to the control diet, quercetin lowered the proliferative index (P = 0.035) regardless of treatment and diminished the AOM-induced elevation in crypt column cell number (P = 0.044) and expansion of the proliferative zone (P = 0.021). The proportion of apoptotic colonocytes in AOM-injected rats increased with quercetin treatment (P = 0.014). Levels of p85 and p85alpha subunits of PI 3-kinase and total Akt were unaffected by dietary quercetin. However, quercetin tended to suppress (P < 0.06) the expression of COX-1 and COX-2. Expression of iNOS was elevated by AOM injection (P = 0.0001). In conclusion, quercetin suppresses the formation of early preneoplastic lesions in colon carcinogenesis, which occurred in concert with reductions in proliferation and increases in apoptosis. It is possible the effects on proliferation and apoptosis resulted from the tendency for quercetin to suppress the expression of proinflammatory mediators.

  11. Effect of quercetin on metallothionein, nitric oxide synthases and cyclooxygenase-2 expression on experimental chronic cadmium nephrotoxicity in rats

    SciTech Connect

    Morales, Ana I.; Vicente-Sanchez, Cesar; Jerkic, Mirjana; Santiago, Jose M.; Sanchez-Gonzalez, Penelope D.; Perez-Barriocanal, Fernando; Lopez-Novoa, Jose M. . E-mail: jmlnovoa@usal.es

    2006-01-15

    Inflammation can play a key role in Cd-induced dysfunctions. Quercetin is a potent oxygen free radical scavenger and a metal chelator. Our aim was to study the effect of quercetin on Cd-induced kidney damage and metallothionein expression. The study was performed in Wistar rats that were administered during 9 weeks with either cadmium (1.2 mg Cd/kg/day, s.c.), quercetin (50 mg/kg/day, i.p.) or cadmium + quercetin. Renal toxicity was evaluated by measuring blood urea nitrogen concentration and urinary excretion of enzymes marker of tubular damage. Endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) renal expression were assessed by Western blot. Renal expression of metallothionein 1 and 2 (MT-1, MT-2) and eNOS mRNA was assessed by Northern blot. Our data demonstrated that Cd-induced renal toxicity was markedly reduced in rats that also received quercetin. MT-1 and MT-2 mRNA levels in kidney were substantially increased during treatment with Cd, being even higher when the animals received Cd and quercetin. Renal eNOS expression was significantly higher in rats receiving Cd and quercetin than in animals receiving Cd alone or in control rats. In the group that received Cd, COX-2 and iNOS expression was markedly higher than in control rats. In the group Cd + quercetin, no changes in COX-2 and iNOS expression were observed compared with the control group. Our results demonstrate that quercetin treatment prevents Cd-induced overexpression of iNOS and COX-2, and increases MT expression. These effects can explain the protection by quercetin of Cd-induced nephrotoxicity.

  12. Benzbromarone, Quercetin, and Folic Acid Inhibit Amylin Aggregation

    PubMed Central

    López, Laura C.; Varea, Olga; Navarro, Susanna; Carrodeguas, José A.; Sanchez de Groot, Natalia; Ventura, Salvador; Sancho, Javier

    2016-01-01

    Human Amylin, or islet amyloid polypeptide (hIAPP), is a small hormone secreted by pancreatic β-cells that forms aggregates under insulin deficiency metabolic conditions, and it constitutes a pathological hallmark of type II diabetes mellitus. In type II diabetes patients, amylin is abnormally increased, self-assembled into amyloid aggregates, and ultimately contributes to the apoptotic death of β-cells by mechanisms that are not completely understood. We have screened a library of approved drugs in order to identify inhibitors of amylin aggregation that could be used as tools to investigate the role of amylin aggregation in type II diabetes or as therapeutics in order to reduce β-cell damage. Interestingly, three of the compounds analyzed—benzbromarone, quercetin, and folic acid—are able to slow down amylin fiber formation according to Thioflavin T binding, turbidimetry, and Transmission Electron Microscopy assays. In addition to the in vitro assays, we have tested the effect of these compounds in an amyloid toxicity cell culture model and we have found that one of them, quercetin, has the ability to partly protect cultured pancreatic insulinoma cells from the cytotoxic effect of amylin. Our data suggests that quercetin can contribute to reduce oxidative damage in pancreatic insulinoma β cells by modulating the aggregation propensity of amylin. PMID:27322259

  13. Benzbromarone, Quercetin, and Folic Acid Inhibit Amylin Aggregation.

    PubMed

    López, Laura C; Varea, Olga; Navarro, Susanna; Carrodeguas, José A; Sanchez de Groot, Natalia; Ventura, Salvador; Sancho, Javier

    2016-01-01

    Human Amylin, or islet amyloid polypeptide (hIAPP), is a small hormone secreted by pancreatic β-cells that forms aggregates under insulin deficiency metabolic conditions, and it constitutes a pathological hallmark of type II diabetes mellitus. In type II diabetes patients, amylin is abnormally increased, self-assembled into amyloid aggregates, and ultimately contributes to the apoptotic death of β-cells by mechanisms that are not completely understood. We have screened a library of approved drugs in order to identify inhibitors of amylin aggregation that could be used as tools to investigate the role of amylin aggregation in type II diabetes or as therapeutics in order to reduce β-cell damage. Interestingly, three of the compounds analyzed-benzbromarone, quercetin, and folic acid-are able to slow down amylin fiber formation according to Thioflavin T binding, turbidimetry, and Transmission Electron Microscopy assays. In addition to the in vitro assays, we have tested the effect of these compounds in an amyloid toxicity cell culture model and we have found that one of them, quercetin, has the ability to partly protect cultured pancreatic insulinoma cells from the cytotoxic effect of amylin. Our data suggests that quercetin can contribute to reduce oxidative damage in pancreatic insulinoma β cells by modulating the aggregation propensity of amylin. PMID:27322259

  14. Quercetin, not caffeine, is a major neuroprotective component in coffee.

    PubMed

    Lee, Moonhee; McGeer, Edith G; McGeer, Patrick L

    2016-10-01

    Epidemiologic studies indicate that coffee consumption reduces the risk of Parkinson's disease and Alzheimer's disease. To determine the factors involved, we examined the protective effects of coffee components. The test involved prevention of neurotoxicity to SH-SY5Y cells that was induced by lipopolysaccharide plus interferon-γ or interferon-γ released from activated microglia and astrocytes. We found that quercetin, flavones, chlorogenic acid, and caffeine protected SH-SY5Y cells from these toxins. They also reduced the release of tumor necrosis factor-α and interleukin-6 from the activated microglia and astrocytes and attenuated the activation of proteins from P38 mitogen-activated protein kinase (MAPK) and nuclear factor kappa light chain enhancer of activated B cells (NFκB). After exposure to toxin containing glial-stimulated conditioned medium, we also found that quercetin reduced oxidative/nitrative damage to DNA, as well as to the lipids and proteins of SH-SY5Y cells. There was a resultant increase in [GSH]i in SH-SY5Y cells. The data indicate that quercetin is the major neuroprotective component in coffee against Parkinson's disease and Alzheimer's disease. PMID:27479153

  15. Quercetin, not caffeine, is a major neuroprotective component in coffee.

    PubMed

    Lee, Moonhee; McGeer, Edith G; McGeer, Patrick L

    2016-10-01

    Epidemiologic studies indicate that coffee consumption reduces the risk of Parkinson's disease and Alzheimer's disease. To determine the factors involved, we examined the protective effects of coffee components. The test involved prevention of neurotoxicity to SH-SY5Y cells that was induced by lipopolysaccharide plus interferon-γ or interferon-γ released from activated microglia and astrocytes. We found that quercetin, flavones, chlorogenic acid, and caffeine protected SH-SY5Y cells from these toxins. They also reduced the release of tumor necrosis factor-α and interleukin-6 from the activated microglia and astrocytes and attenuated the activation of proteins from P38 mitogen-activated protein kinase (MAPK) and nuclear factor kappa light chain enhancer of activated B cells (NFκB). After exposure to toxin containing glial-stimulated conditioned medium, we also found that quercetin reduced oxidative/nitrative damage to DNA, as well as to the lipids and proteins of SH-SY5Y cells. There was a resultant increase in [GSH]i in SH-SY5Y cells. The data indicate that quercetin is the major neuroprotective component in coffee against Parkinson's disease and Alzheimer's disease.

  16. Quercetin metabolites inhibit MMP-2 expression in A549 lung cancer cells by PPAR-γ associated mechanisms.

    PubMed

    Chuang, Cheng-Hung; Yeh, Chiao-Lin; Yeh, Shu-Lan; Lin, En-Shyh; Wang, Li-Yu; Wang, Ying-Hsuna

    2016-07-01

    Our previous study demonstrated that quercetin-metabolite-enriched plasma (QP) but not quercetin itself upregulates peroxisome proliferator-activated receptor gamma (PPAR-γ) expression to induce G2/M arrest in A549 cells. In the present study, we incubated A549 cells with QP as well as quercetin-3-glucuronide (Q3G) and quercetin-3'-sulfate (Q3'S), two major metabolites of quercetin, to investigate the effects of quercetin metabolites on cell invasion and migration, the possible mechanisms and the role of PPAR-γ. We also compared the effects of QP with those of quercetin and troglitazone (TGZ), a PPAR-γ ligand. The results showed that QP significantly suppressed cell invasion and migration, as well as matrix metalloproteinases (MMPs)-2 activity and expression in a dose-dependent manner. The effects of 10% QP on those parameters were similar to those of 10μM quercetin and 20μM TGZ. However, QP and TGZ rather than quercetin itself increased the expressions of nm23-H1 and tissue inhibitor of metalloproteinase (TIMP-2). Furthermore, we demonstrated that Q3G and Q3'S also inhibited the protein expression of MMP-2. GW9662, a PPAR-γ antagonist, significantly diminished such an effect of Q3G and Q3'S. Silencing PPAR-γ expression in A549 cells also significantly diminished the suppression effect of Q3G and Q3'S on MMP-2 expression. Taken together, our study demonstrated that QP inhibited cell invasion and migration through nm23-H1/TIMP-2/MMP-2 associated mechanisms. The upregulation of PPAR-γ by quercetin metabolites such as Q3G and Q3'S could play an important role in the effects of QP. PMID:27260467

  17. Transient increase of interleukin-1β after prolonged febrile seizures promotes adult epileptogenesis through long-lasting upregulating endocannabinoid signaling

    PubMed Central

    Feng, Bo; Tang, Yangshun; Chen, Bin; Xu, Cenglin; Wang, Yi; Dai, Yunjian; Wu, Dengchang; Zhu, Junmin; Wang, Shuang; Zhou, Yudong; Shi, Liyun; Hu, Weiwei; Zhang, Xia; Chen, Zhong

    2016-01-01

    It remains unclear how infantile febrile seizures (FS) enhance adult seizure susceptibility. Here we showed that the transient increase of interleukin-1β (IL-1β) after prolonged FS promoted adult seizure susceptibility, which was blocked by interleukin-1 receptor antagonist (IL-1Ra) within a critical time window. Postnatal administered IL-1β alone mimicked the effect of FS on adult seizure susceptibility. IL-1R1 knockout mice were not susceptible to adult seizure after prolonged FS or IL-1β treatment. Prolonged FS or early-life IL-1β treatment increased the expression of cannabinoid type 1 receptor (CB1R) for over 50 days, which was blocked by IL-1Ra or was absent in IL-1R1 knockout mice. CB1R antagonist, knockdown and endocannabinoid synthesis inhibitor abolished FS or IL-1β-enhanced seizure susceptibility. Thus, this work identifies a pathogenic role of postnatal IL-1β/IL-1R1 pathway and subsequent prolonged prominent increase of endocannabinoid signaling in adult seizure susceptibility following prolonged FS, and highlights IL-1R1 as a potential therapeutic target for preventing the development of epilepsy after infantile FS. PMID:26902320

  18. Acidic retinoids in small amounts promote retinyl ester formation in neonatal lung, with transient increases in retinoid homeostatic gene expression

    PubMed Central

    2013-01-01

    Background Mixing a small proportion, 10%, of retinoic acid (RA) into an oral dose of vitamin A (VA) has been shown to markedly increase retinol uptake and retinyl ester (RE) formation in the neonatal lung, as compared to VA given alone. Concomitantly, several retinoid homeostatic genes, lecithin:retinol acyltransferase (LRAT), RA-4-hydroxylase (CYP26B1), and stimulated by retinoic acid gene-6 (STRA6) were upregulated. However, whether multiple doses may act accumulatively and whether less than 10% RA can be used has not been determined. Methods Neonatal rats were treated once on postnatal day (PD) 4 or PD14 with VA alone or VA combined with 10% RA (VARA10%) or a stable analog, Am580 (VAAm10%), or they were treated with multiple doses on PD4, 7, 11, and 14. Results RE increased cumulatively with multiple dosing. However, LRAT, CYP26B1 and STRA6 mRNA levels were similar for single and multiple treatments, indicating a transient noncumulative impact on gene expression. Lung RE was elevated with as little as 0.5% RA (P < 0.05) in a single dosing study. Whereas all concentrations of VARA elevated lung RE in single dosing studies, only 10% RA increased lung RE after multiple dosing, suggesting an attenuation of RA action with repeated dosing. In contrast, VAAm10%, 2%, and 1% all significantly increased lung RE after multiple doses (P < 0.05), while also increasing the expression of LRAT and CYP26B1. Conclusions These results indicate that the neonatal lung is very sensitive to acidic retinoid exposure and suggest that a VA combined with a very small fraction of acidic retinoid could be effective in increasing the lung’s storage pool of VA. PMID:24351038

  19. Effects of O-methylated metabolites of quercetin on oxidative stress, thermotolerance, lifespan and bioavailability on Caenorhabditis elegans.

    PubMed

    Surco-Laos, Felipe; Cabello, Juan; Gómez-Orte, Eva; González-Manzano, Susana; González-Paramás, Ana M; Santos-Buelga, Celestino; Dueñas, Montserrat

    2011-08-01

    Quercetin is a major flavonoid in the human diet and the most commonly used in studies of biological activity. Most of the knowledge about its biological effects has originated from in vitro studies while in vivo data are scarce. Quercetin mostly occurs in foodstuffs as glycosides that are deglycosylated during absorption and further submitted to different conjugation reactions. Methylation to isorhamnetin (quercetin 3'-O-methylether) or tamarixetin (quercetin 4'-O-methylether) seems to be an important conjugation process in quercetin metabolism. In this work, the effects of quercetin and its 3'- and 4'-O-methylated metabolites on the phenotypic characteristics, stress oxidative resistance, thermotolerance and lifespan of the model organism Caenorhabditis elegans have been assessed. The three assayed flavonols significantly prolonged the lifespan of this nematode with an increase from 11% to 16% in the mean lifespan with respect to controls. However, only quercetin significantly increased the reproductive capacity of the worm and enlarged the body size. Exposure to the assayed flavonols also increased significantly the resistance against thermal and juglone-induced oxidative stress, although differences were found depending on the stage of development of the worm. Thus, quercetin offered greater protection when thermal stress was applied in the 1st day of adulthood, whereas tamarixetin was more efficient in worms submitted to stress in the 6th day of adulthood. Similarly, significantly greater protection was provided by quercetin than by its methylated derivatives at the 1st day of adulthood, whilst quercetin and isorhamnetin were equally efficient when the oxidative stress was induced in the 6th of day of adulthood. Further evidence of antioxidant protection was obtained checking the oxidation status of proteins by the OxyBlot™ detection kit. Analyses by HPLC-DAD-ESI/MS confirmed that the three flavonols were taken up by C. elegans leading to the formation of

  20. Role of Quercetin Benefits in Neurodegeneration.

    PubMed

    Elumalai, Preetham; Lakshmi, Sreeja

    2016-01-01

    Neurodegenerative disorders are often life threatening and hired as an economic burden to the health-care system. Nutritional interventions principally involving polyphenols were practiced to arrest or reverse the age-related health disorders. Flavonoids, a class of dietary polyphenols, are rising to superstardom in preventing brain disorders with their potent antioxidant defense mechanism. Quercetin is a ubiquitous flavonoid reported to have all-natural myriad of health benefits. Citrus fruits, apple, onion, parsley, berries, green tea, and red wine comprise the major dietary supplements of quercetin apart from some herbal remedies like Ginkgo biloba. Appositeness of quercetin in reducing risks of neurodegenerative disorders, cancer, cardiovascular diseases, allergic disorders, thrombosis, atherosclerosis, hypertension, and arrhythmia, to name a few, is attributed to its highly pronounced antioxidant and anti-inflammatory properties. Neurodegeneration, characterized by progressive deterioration of the structure and function of neurons, is crucially accompanied by severe cognitive deficits. Aging is the major risk factor for neurodegenerative disorders in Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD) being coequal high hands. Oxidative stress and mitochondrial dysfunction are the key players in triggering neurodegeneration. The upsurge of neurodegenerative disorders is always appalling since there exists a paucity in effective treatment practices. Past few years' studies have underpinned the mechanisms through which quercetin boons the brain health in many aspects including betterment in cognitive output. Undoubtedly, quercetin will be escalating as an arable field, both in scientific research and in pharmacological and clinical applications. PMID:27651256

  1. Modulation of paraoxonase 2 (PON2) in mouse brain by the polyphenol quercetin: a mechanism of neuroprotection?

    PubMed Central

    Costa, Lucio G.; Tait, Leah; de Laat, Rian; Dao, Khoi; Giordano, Gennaro; Pellacani, Claudia; Cole, Toby B.; Furlong, Clement E.

    2013-01-01

    Quercetin is a common flavonoid polyphenol which has been shown to exert neuroprotective actions in vitro and in vivo. Though quercetin has antioxidant properties, it has been suggested that neuroprotection may be ascribed to its ability of inducing the cell’s own defense mechanisms. The present study investigated whether quercetin could increase the levels of paraoxonase 2 (PON2), a mitochondrial enzyme expressed in brain cells, which has been shown to have potent antioxidant properties. PON2 protein, mRNA, and lactonase activity were highest in mouse striatal astrocytes. Quercetin increased PON2 levels, possibly by activating the JNK/AP-1 pathway. The increased PON2 levels induced by quercetin resulted in decreased oxidative stress and ensuing toxicity induced by two oxidants. The neuroprotective effect of quercetin was significantly diminished in cells from PON2 knockout mice. These findings suggest that induction of PON2 by quercetin represents an important mechanism by which this polyphenol may exert its neuroprotective action. PMID:23743621

  2. Axial Stretch of Rat Single Ventricular Cardiomyocytes Causes an Acute and Transient Increase in Ca2+ Spark Rate

    PubMed Central

    Iribe, Gentaro; Ward, Christopher W.; Camelliti, Patrizia; Bollensdorff, Christian; Mason, Fleur; Burton, Rebecca A.B.; Garny, Alan; Morphew, Mary K.; Hoenger, Andreas; Lederer, W. Jonathan; Kohl, Peter

    2010-01-01

    We investigate acute effects of axial stretch, applied by carbon fibers (CFs), on diastolic Ca2± spark rate in rat isolated cardiomyocytes. CFs were attached either to both cell ends (to maximize the stretched region), or to the center and one end of the cell (to compare responses in stretched and nonstretched half-cells). Sarcomere length was increased by 8.01 ± 0.94% in the stretched cell fraction, and time series of XY confocal images were recorded to monitor diastolic Ca2± spark frequency and dynamics. Whole-cell stretch causes an acute increase of Ca2± spark rate (to 130.7 ± 6.4%) within 5 seconds, followed by a return to near background levels (to 104.4±5.1%) within 1 minute of sustained distension. Spark rate increased only in the stretched cell region, without significant differences in spark amplitude, time to peak, and decay time constants of sparks in stretched and nonstretched areas. Block of stretch-activated ion channels (2 gmol/L GsMTx-4), perfusion with Na±/Ca2±-free solution, and block of nitric oxide synthesis (1 mmol/L L-NAME) all had no effect on the stretch-induced acute increase in Ca2± spark rate. Conversely, interference with cytoskeletal integrity (2 hours of 10 gmol/L colchicine) abolished the response. Subsequent electron microscopic tomography confirmed the close approximation of microtubules with the T-tubular–sarcoplasmic reticulum complex (to within · 10−8m). In conclusion, axial stretch of rat cardiomyocytes acutely and transiently increases sarcoplasmic reticulum Ca2± spark rate via a mechanism that is independent of sarcolemmal stretch-activated ion channels, nitric oxide synthesis, or availability of extracellular calcium but that requires cytoskeletal integrity. The potential of microtubule-mediated modulation of ryanodine receptor function warrants further investigation. PMID:19197074

  3. Pressure changes within the sac of human cerebral aneurysms in response to artificially induced transient increases in systemic blood pressure.

    PubMed

    Hasan, David M; Hindman, Bradley J; Todd, Michael M

    2015-08-01

    Formation and rupture of cerebral aneurysms have been associated with chronic hypertension. The effect of transient increase in blood pressure and its effect on intra-aneurysmal hemodynamics have not been studied. We examined the effects of controlled increases in blood pressure on different pressure parameters inside the sac of human cerebral aneurysms and corresponding parent arteries using invasive technology. Twelve patients (10 female, 2 male, age 54±15 years) with unruptured cerebral aneurysms undergoing endovascular coiling were recruited. Dual-sensor microwires with the capacity to simultaneously measure flow velocity and pressure were used to measure systolic, diastolic, and mean pressure inside the aneurysm sac and to measure both pressures and flow velocities in the feeder vessel just outside the aneurysm. These pressures were recorded simultaneously with pressures from a radial arterial catheter. Measurements were taken at baseline and then during a gradual increase in systemic systolic blood pressure to a target value of ≈25 mm Hg above baseline, using a phenylephrine infusion. The dose needed to achieve the required increase in radial arterial systolic blood pressure was 0.8±0.2 μg/kg/min. There was a clear linear relationship between changes in radial and aneurysmal pressures with substantial patient-by-patient variation in the slopes of those relationships. The overall increases in systolic and mean pressures in both radial artery and in the aneurysms were similar. Pressures in the aneurysm and in the parent vessels were similar. Peak and mean flow velocities in the parent arteries did not change significantly with phenylephrine infusion, nor did vessel diameters as measured angiographically.

  4. Quercetin Directly Interacts with Vitamin D Receptor (VDR): Structural Implication of VDR Activation by Quercetin

    PubMed Central

    Lee, Ki-Young; Choi, Hye-Seung; Choi, Ho-Sung; Chung, Ka Young; Lee, Bong-Jin; Maeng, Han-Joo; Seo, Min-Duk

    2016-01-01

    The vitamin D receptor (VDR) is a member of the nuclear receptor (NR) superfamily. The VDR binds to active vitamin D3 metabolites, which stimulates downstream transduction signaling involved in various physiological activities such as calcium homeostasis, bone mineralization, and cell differentiation. Quercetin is a widely distributed flavonoid in nature that is known to enhance transactivation of VDR target genes. However, the detailed molecular mechanism underlying VDR activation by quercetin is not well understood. We first demonstrated the interaction between quercetin and the VDR at the molecular level by using fluorescence quenching and saturation transfer difference (STD) NMR experiments. The dissociation constant (Kd) of quercetin and the VDR was 21.15 ± 4.31 μM, and the mapping of quercetin subsites for VDR binding was performed using STD-NMR. The binding mode of quercetin was investigated by a docking study combined with molecular dynamics (MD) simulation. Quercetin might serve as a scaffold for the development of VDR modulators with selective biological activities. PMID:26902087

  5. Quercetin protects human hepatoma HepG2 against oxidative stress induced by tert-butyl hydroperoxide

    SciTech Connect

    Alia, Mario . E-mail: luisgoya@if.csic.es

    2006-04-15

    Flavonols such as quercetin, have been reported to exhibit a wide range of biological activities related to their antioxidant capacity. The objective of the present study was to investigate the protective effect of quercetin on cell viability and redox status of cultured HepG2 cells submitted to oxidative stress induced by tert-butyl hydroperoxide. Concentrations of reduced glutathione and malondialdehyde, generation of reactive oxygen species and activity and gene expression of antioxidant enzymes were used as markers of cellular oxidative status. Pretreatment of HepG2 with 10 {mu}M quercetin completely prevented lactate dehydrogenase leakage from the cells. Pretreatment for 2 or 20 h with all doses of quercetin (0.1-10 {mu}M) prevented the decrease of reduced glutathione and the increase of malondialdehyde evoked by tert-butyl hydroperoxide in HepG2 cells. Reactive oxygen species generation induced by tert-butyl hydroperoxide was significantly reduced when cells were pretreated for 2 or 20 h with 10 {mu}M and for 20 h with 5 {mu}M quercetin. Finally, some of the quercetin treatments prevented the significant increase of glutathione peroxidase, superoxide dismutase, glutathione reductase and catalase activities induced by tert-butyl hydroperoxide. Gene expression of antioxidant enzymes was also affected by the treatment with the polyphenol. The results of the biomarkers analyzed clearly show that treatment of HepG2 cells in culture with the natural dietary antioxidant quercetin strongly protects the cells against an oxidative insult.

  6. Therapeutic detoxification of quercetin against carbon tetrachloride-induced acute liver injury in mice and its mechanism*

    PubMed Central

    Zhang, Jia-qi; Shi, Liang; Xu, Xi-ning; Huang, Si-chong; Lu, Bin; Ji, Li-li; Wang, Zheng-tao

    2014-01-01

    This study observes the therapeutic detoxification of quercetin, a well-known flavonoid, against carbon tetrachloride (CCl4) induced acute liver injury in vivo and explores its mechanism. Quercetin decreased CCl4-increased serum activities of alanine and aspartate aminotransferases (ALT/AST) when orally taken 30 min after CCl4 intoxication. The results of a histological evaluation further evidenced the ability of quercetin to protect against CCl4-induced liver injury. Quercetin decreased the CCl4-increased malondialdehyde (MDA) and reduced the glutathione (GSH) amounts in the liver. It also reduced the enhanced immunohistochemical staining of the 4-hydroxynonenal (4-HNE) in the liver induced by CCl4. Peroxiredoxin (Prx) 1, 2, 3, 5, 6, thioredoxin reductase 1 and 2 (TrxR1/2), thioredoxin 1 and 2 (Trx1/2), nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) all play critical roles in maintaining cellular redox homeostasis. Real-time polymerase chain reaction (PCR) results demonstrated that quercetin reversed the decreased mRNA expression of all those genes induced by CCl4. In conclusion, our results demonstrate that quercetin ameliorates CCl4-induced acute liver injury in vivo via alleviating oxidative stress injuries when orally taken after CCl4 intoxication. This protection may be caused by the elevation of the antioxidant capacity induced by quercetin. PMID:25471833

  7. Synergy and Mode of Action of Ceftazidime plus Quercetin or Luteolin on Streptococcus pyogenes

    PubMed Central

    Siriwong, Supatcharee; Thumanu, Kanjana; Hengpratom, Tanaporn; Eumkeb, Griangsak

    2015-01-01

    Streptococcus pyogenes causes streptococcal toxic shock syndrome. The recommended therapy has been often failure through the interfering of beta-lactamase-producing bacteria (BLPB). The present study was to investigate antibacterial activity, synergy, and modes of action of luteolin and quercetin using alone and plus ceftazidime against S. pyogenes. The MICs of ceftazidime, luteolin, and quercetin against all S. pyogenes were 0.50, 128, and 128 µg mL−1, respectively. A synergistic effect was exhibited on luteolin and quercetin plus ceftazidime against these strains at fractional inhibitory concentration indices 0.37 and 0.27, respectively, and was confirmed by the viable count. These combinations increased cytoplasmic membrane (CM) permeability, caused irregular cell shape, peptidoglycan, and CM damage, and decreased nucleic acid but increased proteins in bacterial cells. Enzyme assay demonstrated that these flavonoids had an inhibitory activity against β-lactamase. In summary, this study provides evidence that the inhibitory mode of action of luteolin and quercetin may be mediated via three mechanisms: (1) inhibiting of peptidoglycan synthesis, (2) increasing CM permeability, and (3) decreasing nucleic acid but increasing the protein contents of bacterial cells. So, luteolin and quercetin propose the high potential to develop adjunct to ceftazidime for the treatment of coexistence of the BLPB and S. pyogenes infections. PMID:26576195

  8. Quercetin Induces Dose-Dependent Differential Morphological and Proliferative Changes in Rat Uteri in the Presence and in the Absence of Estrogen.

    PubMed

    Shahzad, Huma; Giribabu, Nelli; Sekaran, Muniandy; Salleh, Naguib

    2015-12-01

    Quercetin could have profound effects on uterine morphology and proliferation, which are known to be influenced by estrogen. This study investigated the effect of quercetin on these uterine parameters in the presence and in the absence of estrogen. Ovariectomized adult female rats received peanut oil, quercetin (10, 50, and 100 mg/kg/day), estrogen, or estrogen+quercetin (10, 50, or 100 mg/kg/day) treatment for 7 consecutive days. At the end of the treatment, uteri were harvested for histological and molecular biological analyses. Distribution of proliferative cell nuclear antigen (PCNA) protein in the uterus was observed by immunohistochemistry. Levels of expression of PCNA protein and mRNA in uterine tissue homogenates were determined by Western blotting and real-time polymerase chain reaction, respectively. Our findings indicated that administration of 10 mg/kg/day of quercetin either alone or with estrogen resulted in decreased uterine expression of PCNA protein and mRNA with the percentage of PCNA-positive cells in uterine luminal and glandular epithelia markedly reduced compared with estrogen-only treatment. Changes in uterine morphology were the opposite of changes observed following estrogen treatment. Treatment with 100 mg/kg/day of quercetin either alone or with estrogen resulted in elevated PCNA protein and mRNA expression. In addition, the percentages of PCNA-positive cells in the epithelia, which line the lumen and glands, were increased with morphological features mimicking changes that occur following estrogen treatment. Following 50 mg/kg/day quercetin treatment, the changes observed were in between those changes that occur following 10 and 100 mg/kg/day quercetin treatment. In conclusion, changes in uterine morphology and proliferation following 10 mg/kg/day quercetin treatment could be attributed to quercetin's antiestrogenic properties, while changes that occur following 100 mg/kg/day quercetin treatment could be attributed to

  9. Transient increase in the levels of gamma-tubulin complex in reorientation of cortical microtubules by gravity in azuki bean epicotyls

    NASA Astrophysics Data System (ADS)

    Soga, Kouichi; Kotake, Toshihisa; Wakabayashi, Kazuyuki; Kamisaka, Seiichiro; Hoson, Takayuki

    Azuki bean (Vigna angularis Ohwi et Ohashi) seedlings were exposed to centrifugal hypergravity, and the changes in the orientation of cortical microtubules and the expression of genes cording γ-tubulin complex (VaTUBG and VaSpc98p) were examined. By 300 g treatment, the percentage of cells with transverse microtubules was decreased, while that with longitudinal microtubules was increased in epicotyls. Hypergravity increased the expression of VaTUBG and VaSpc98p transiently. Also, the expression of both genes was increased transiently by removal of hypergravity stimulus. Lanthanum and gadolinium ions, potential blockers of mechanosensitive calcium ion-permeable channels (mechanoreceptors), nullified reorientation of microtubules as well as up-regulation of expression of VaTUBG and VaSpc98p by hypergravity. These results suggest that mechanoreceptors on the plasma membrane may perceive the gravity signal, which leads to reorientation of cortical microtubules by transiently stimulating the formation of γ-tubulin complex.

  10. Hyaluronic acid-quercetin conjugate micelles: synthesis, characterization, in vitro and in vivo evaluation.

    PubMed

    Pang, Xin; Lu, Zhen; Du, Hongliang; Yang, Xiaoye; Zhai, Guangxi

    2014-11-01

    A tumor cell-targeted prodrug was developed for quercetin, using hyaluronic acid as polymeric carrier. Hyaluronic acid-quercetin (HA-QT) bioconjugates were synthesized by linking the hydroxy of quercetin via a succinate ester to adipic dihydrazide-modified hyaluronic acid. The mirco-morphology demonstrated that the prepared prodrug could form self-assembled micelles possessing spherical shape, 172.1 nm average diameter and -20.30 mV surface potential. The HA-QT micelles exhibited significant sustained and pH-dependent drug release behaviors without dramatic initial burst. Compared to free quercetin solution, the HA-QT micelles were found a 4 times increase in cytotoxicity on MCF-7 cells (CD44-overexpressing cell lines), while weak enhancement in inhibitory activity was observed towards L929 cells (CD44 deficient cell lines). Promisingly, 20.1-fold increase in the half-life and 4.9-fold increase in the area-under-the-curve (AUC) of quercetin were achieved for the HA-QT micelles compared with the parent drug. In addition, the HA-QT micelles also showed excellent inhibition effect on tumor growth in H22 tumor-bearing mice. Hemolytic toxicity and vein irritation assay further suggested that the HA-QT micelles were a safe and potent drug delivery system for targeted antitumor therapy. PMID:25454664

  11. Metabonomic analysis of quercetin against the toxicity of chronic exposure to low-level dichlorvos in rats via ultra-performance liquid chromatography-mass spectrometry.

    PubMed

    Wang, Hong; Li, Sifan; Qi, Lei; Xu, Wei; Zeng, Yan; Hou, Yurong; Zhao, Xiujuan; Sun, Changhao

    2014-03-01

    This study aims to determine whether quercetin elicits a protective effect against the toxicity of chronic exposure to low-level DDVP using metabonomic technology. Rats were randomly assigned into the control, DDVP-treated, quercetin-treated, and quercetin plus DDVP-treated groups. DDVP and quercetin were given to rats daily via drinking water and gavage respectively for 90 days. Eighteen metabolites, including the biomarkers of DDVP exposure (dimethyl phosphate, DMP) and quercetin exposure (quercetin and isorhamnetina), were identified from the metabonomic profiles of rat urine using ultra-performance liquid chromatography-mass spectrometry. Compared with the control group, the DDVP-treated group showed statistically significantly increased intensities of indoxyl sulfate, estrone sulfate, cholic acid, deoxycholic acid, p-cresol, p-cresol sulfate, and orotic acid but decreased intensities of suberic acid, citric acid, sebacic acid, hippuric acid, taurine, phosphocreatine, 3-hydroxyanthranilic acid, and kynurenic acid. The tendency of the aforesaid metabolites to change was significantly ameliorated in the quercetin (50mg/kg·bw) plus DDVP (7.2mg/kg·bw)-treated group compared with the DDVP-treated group. However, the levels of these metabolites in the quercetin plus DDVP-treated groups were still significantly different from those of the control group. These results indicate that quercetin has a partial protective effect on DDVP-induced toxicity.

  12. Inhibition of lung cancer cell growth by quercetin glucuronides via G2/M arrest and induction of apoptosis.

    PubMed

    Yang, Jen-Hung; Hsia, Te-Chun; Kuo, Hsiu-Maan; Chao, Pei-Dawn Lee; Chou, Chi-Chung; Wei, Yau-Huei; Chung, Jing-Gung

    2006-02-01

    Lung cancer is the leading cause of cancer death in many developed countries, including Taiwan. Quercetin, a widely distributed bioflavonoid, is well known to induce growth inhibition in a variety of human cancer cells. Quercetin glucuronides are the main circulating metabolites after dietary supplements with quercetin in humans. However, there is little information available as to how quercetin glucuronides affect human cancer cells. We investigated the effects of quercetin glucuronides in a human lung cancer cell line NCI-H209. We checked the cell viability, cell cycle checkpoint proteins, pro- and antiapoptotic proteins, caspase-3 activity, and gene expression by flow cytometry and Western blot. The viability of cells decreased in a dose- and time-dependent manner. Cell cycle analysis revealed a significant increase of the proportion of cells in G2/M phase and subG0/G1 phase (corresponding to apoptotic cells). Moreover, quercetin glucuronides increased the expressions of cyclin B, Cdc25c-ser-216-p, and Wee1 proteins, indicating the G2/M arrest. We also demonstrated a concurrent decrease of the mitochondrial membrane potential, release of cytochrome c, up-regulation of Bax, down-regulation of Bcl-2, and activation of caspase-3, and subsequently, cleavage of poly(ADP-ribose) polymerase. In addition, quercetin glucuronide-induced apoptosis was totally blocked by the broad-spectrum caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp fluoromethylketone. Taken together, we demonstrated that quercetin glucuronides inhibited proliferation through G2/M arrest of the cell cycle and induced apoptosis via caspase-3 cascade in the human lung cancer cell line NCI-H209. Delineation of the biological effects of specific major quercetin metabolites on chemotherapeutic potential or chemoprevention of human cancers warrants further investigation. PMID:16280456

  13. HPV-18 transformed cells fail to arrest in G1 in response to quercetin treatment.

    PubMed

    Beniston, R G; Campo, M S

    2005-05-01

    Previous work with primary human keratinocytes demonstrated that quercetin, a potent mutagen found in high levels in bracken fern (Pteridium aquilinum), arrested cells in G1 with concomitant elevation of the cyclin-dependent kinase inhibitor (cdki) p27Kip1. Expression of the human papillomavirus type 16 (HPV-16) E6 and E7 oncoproteins, under transcriptional control of a heterologous promoter, in transformed keratinocytes failed to abrogate this arrest [Beniston, R., Campo, M.S., 2003. Quercetin elevates p27Kip1 and arrests both primary and HPV-16 E6/E7 transformed human keratinocytes in G1. Oncogene 22, 5504-5514]. Given the link between papillomavirus infection, bracken fern in the diet and cancer of the oesophagus in humans, we wished to investigate further whether cells transformed by the whole genome of HPV-16 or HPV-18, with E6 and E7 under the transcriptional control of their respective homologous promoters, would be similarly arrested in G1 by quercetin. In agreement with earlier work, quercetin arrested HPV-16 transformed cells in G1 with an increase in the cyclin-dependent kinase inhibitor p27Kip1. However, HPV-18 transformed cells did not arrest after quercetin treatment. The failure of HPV-18 transformed cells to arrest in G1 was linked to the up-regulation of the HPV-18 long control region (LCR) by quercetin, maintaining high expression of the viral transforming proteins. Transcriptional up-regulation of the HPV-18 LCR was mediated by a "quercetin responsive element" homologous to the one identified previously in the bovine papillomavirus type 4 (BPV-4) LCR.

  14. Co-encapsulation of biodegradable nanoparticles with silicon quantum dots and quercetin for monitored delivery.

    PubMed

    Wang, Qi; Bao, Yongping; Ahire, Jayshree; Chao, Yimin

    2013-03-01

    Polymer nanoparticles have emerged as a promising new strategy for the efficient delivery of drugs. They have several advantages when used as drug carriers, such as high stability, high capacity, improvement of drug bioavailability, as well as allowing for sustained drug release. Quercetin has therapeutic potential as an anticancer drug, but has poor solubility and low bioavailability. In this study it is shown that co-encapsulation of quercetin and fluorescent Silicon quantum dots (SiQDs) in poly (ethylene glycol)-block-polylactide (PEG-PLA) nanoparticles can be used for simultaneous in vitro imaging and to improve the biocompatibility of quercetin. Fluorescent imaging with SiQDs can provide a new concept to monitor the delivery of anti-cancer drugs. The nanoparticles are synthesized based on the double emulsion method and are extensively characterized and assayed for cytotoxicity in vitro. HepG2 cells are incubated with quercetin and SiQDs dual-loaded PEG-PLA nanoparticles, resulting in a red fluorescent staining which can be detected with a confocal microscope. PEG-PLA nanoparticle encapsulated quercetin suppresses human hepatoma HepG2 cell proliferation more effectively than the free-standing form. In addition, nanoparticle-encapsulated quercetin significantly inhibits hydrogen peroxide-induced DNA damage in HepG2 cells. These data show that nanocapsulated quercetin possesses the potential bioactivity to reduce the drug dosage frequency, as well as increase patient compliance. The combination of polymeric nanoparticles and semiconductor quantum dots can allow monitoring of delivery, improve aqueous solubility, and enhance biocompatibility. Such nanoparticulated systems could shape the future of drug delivery.

  15. Quercetin alleviates pulmonary angiogenesis in a rat model of hepatopulmonary syndrome

    PubMed Central

    Li, X.; Chen, Y.; Wang, L.; Shang, G.; Zhang, C.; Zhao, Z.; Zhang, H.; Liu, A.

    2016-01-01

    Quercetin shows protective effects against hepatopulmonary syndrome (HPS), as demonstrated in a rat model. However, whether these effects involve pulmonary vascular angiogenesis in HPS remains unclear. Therefore, this study aimed to assess the effect of quercetin on pulmonary vascular angiogenesis and explore the underlying mechanisms. Male Sprague-Dawley rats weighing 200-250 g underwent sham operation or common bile duct ligation (CBDL). Two weeks after surgery, HIF-1α and NFκB levels were assessed in rat lung tissue by immunohistochemistry and western blot. Then, CBDL and sham-operated rats were further divided into 2 subgroups each to receive intraperitoneal administration of quercetin (50 mg/kg daily) or 0.2% Tween for two weeks: Sham (Sham+Tween; n=8), CBDL (CBDL+Tween; n=8), Q (Sham+quercetin; n=8), and CBDL+Q (CBDL+quercetin; n=8). After treatment, lung tissue specimens were assessed for protein (immunohistochemistry and western blot) and/or gene expression (quantitative real-time PCR) levels of relevant disease markers, including VEGFA, VEGFR2, Akt/p-Akt, HIF-1α, vWf, and IκB/p-IκB. Finally, arterial blood was analyzed for alveolar arterial oxygen pressure gradient (AaPO2). Two weeks after CBDL, HIF-1α expression in the lung decreased, but was gradually restored at four weeks. Treatment with quercetin did not significantly alter HIF-1α levels, but did reduce AaPO2 as well as lung tissue NF-κB activity, VEGFA gene and protein levels, Akt activity, and angiogenesis. Although hypoxia is an important feature in HPS, our findings suggest that HIF-1α was not the main cause for the VEGFA increase. Interestingly, quercetin inhibited pulmonary vascular angiogenesis in rats with HPS, with involvement of Akt/NF-κB and VEGFA/VEGFR-2 pathways. PMID:27383124

  16. Alleviative effects of quercetin and onion on male reproductive toxicity induced by diesel exhaust particles.

    PubMed

    Izawa, Hiromi; Kohara, Machiko; Aizawa, Koichi; Suganuma, Hiroyuki; Inakuma, Takahiro; Watanabe, Gen; Taya, Kazuyoshi; Sagai, Masaru

    2008-05-01

    Diesel exhaust particles (DEPs) are particulate matter from diesel exhaust that contain many toxic compounds, such as polyaromatic hydrocarbons (PAHs). Some toxicities of PAH are thought to be expressed via aryl hydrocarbon receptors (AhRs). The male reproductive toxicity of DEPs might depend on AhR activation induced by PAHs. We hypothesized that AhR antagonists protect against the male reproductive toxicity of DEPs. Quercetin is a flavonoid and a well-known AhR antagonist, while onion contains many flavonoids, including quercetin. Hence, we examined whether quercetin and onion have alleviative effects against the male reproductive toxicity induced by DEPs. BALB/c male mice were fed quercetin- or onion-containing diets and received 10 injections of DEP suspension or vehicle into the dorsal subcutaneous layer over 5 weeks. The mice were euthanized at 2 weeks, after the last treatment, and their organs were collected. Daily sperm production and total incidence of sperm abnormalities were significantly affected in the DEP groups as compared with the vehicle group, but the total incidence of sperm abnormalities in the quercetin + DEP-treated mice was significantly reduced as compared with the DEP-treated mice. The numbers of Sertoli cells were significantly decreased in DEP-treated mice as compared with the vehicle-treated mice, but, the numbers of Sertoli cells were significantly increased in the quercetin and the onion + DEP-treated mice as compared with the DEP-treated mice. These results clearly indicate alleviative effects of quercetin and onion against the male reproductive toxicity induced by DEP.

  17. Therapeutic effects of quercetin against bisphenol A induced testicular damage in male Sprague Dawley rats.

    PubMed

    Jahan, Sarwat; Ain, Qurat Ul; Ullah, Hizb

    2016-01-01

    The present study was designed to investigate protective effects of quercetin against bisphenol A (BPA) induced testicular toxicity in male Sprague Dawley rats. Twenty adult male rats were divided into four groups. The first group served as the control and was provided with normal saline. The second group of rats was treated with 50 mg/kg of BPA dissolved in alcoholic saline. The third group received oral gavage of 50 mg/kg quercetin while the fourth group was treated with quercetin (50 mg/kg) along with BPA (50 mg/kg). All of the treatments were carried out for 52 days. Testicular tissues and epididymis were used for histology while blood plasma was used for hormonal and biochemical analysis. BPA administration resulted in a significant reduction in seminiferous tubule diameter and epithelial height with impaired spermatogenesis. Quercetin treatment resulted in restoration of spermatogenesis and reversal of histological damage. In addition, BPA treatment significantly reduced (p < 0.05) plasma testosterone level (ng/ml) while estrogen was not affected. Similarly, BPA caused a significant alteration in the lipid profile. Interestingly, quercetin treatment led to a marked increase in plasma testosterone, decrease in estrogen concentration, as well as a normalized lipid profile. In conclusion, results indicated that BPA administration induces toxic effects on testis and epididymis, impairs spermatogenesis, with an imbalance in hormonal levels and lipid profile while quercetin amended these toxic effects by restoring normal spermatogenesis, testicular tissue damage, and hormonal levels. This suggests that quercetin may be a potential therapeutic against BPA induced testicular toxicity. PMID:26787223

  18. Inhibition of the transient receptor potential melastatin-2 channel causes increased DNA damage and decreased proliferation in breast adenocarcinoma cells

    PubMed Central

    HOPKINS, MANDI M.; FENG, XIAOXING; LIU, MENGWEI; PARKER, LAUREN P.; KOH, DAVID W.

    2015-01-01

    Transient receptor potential, melastatin-2 (TRPM2) is a plasma membrane cation channel with important roles in sensory functions and promoting cell death. However, we demonstrated here that TRPM2 was present in the nuclei of MCF-7 and MDA-MB-231 human breast adenocarcinoma cells, and its pharmacologic inhibition or RNAi silencing caused decreased cell proliferation. Neither an effect on proliferation nor a localization of TRPM2 in the nucleus was observed in noncancerous HMEC and MCF-10A human mammary epithelial cells. Investigation of possible effects of TRPM2 function in the nucleus demonstrated that pharmacologic inhibition or RNAi silencing of TRPM2 in MCF-7 and MDA-MB-231 human breast adenocarcinoma cells caused up to 4-fold increases in DNA damage levels, as compared to noncancerous breast cells after equivalent treatments. These results indicate that TRPM2 has a novel nuclear function in human breast adenocarcinoma cells that facilitates the integrity of genomic DNA, a finding that is distinct from its previously reported role as a plasma membrane cation channel in noncancerous cells. In summary, we report here a novel effect promoted by TRPM2, where it functions to minimize DNA damage and thus may have a role in the protection of genomic DNA in breast cancer cells. Our study therefore provides compelling evidence that TRPM2 has a unique role in breast adenocarcinoma cells. Accordingly, these studies suggest that TRPM2 is a potential therapeutic target, where its pharmacologic inhibition may provide an innovative strategy to selectively increase DNA damage levels in breast cancer cells. PMID:25760245

  19. Transient attention does increase perceived contrast of suprathreshold stimuli: a reply to Prinzmetal, Long, and Leonhardt (2008).

    PubMed

    Carrasco, Marisa; Fuller, Stuart; Ling, Sam

    2008-10-01

    Carrasco, Ling, and Read (2004) showed that transient attention increases perceived contrast. However, Prinzmetal, Long, and Leonhardt (2008) suggest that for targets of low visibility, observers may bias their response toward the cued location, and they propose a cue-bias explanation for our previous results. Our response is threefold. First, we outline several key methodological differences between the studies that could account for the different results. We conclude that the cue-bias hypothesis is a plausible explanation for Prinzmetal et al.'s (2008) results, given the characteristics of their stimuli, but not for the studies by Carrasco and colleagues, in which the stimuli were suprathreshold (Carrasco, Ling, & Read, 2004; Fuller, Rodriguez, & Carrasco, 2008; Ling & Carrasco, 2007). Second, we conduct a study to show that the stimuli used in our previous studies are not near-threshold, but suprathreshold (Experiment 1, Phase 1). Furthermore, we found an increase in apparent contrast for a high-contrast stimulus when it was precued, but not when it was postcued, providing more evidence against a cue-bias hypothesis (Experiment 1, Phase 2). We also show that the visibility of the stimuli in Prinzmetal et al. (2008) was much lower than that of Carrasco, Ling, and Read, rendering their stimuli susceptible to their cue-bias explanation (Experiment 2). Third, we present a comprehensive summary of all the control conditions used in different labs that have ruled out a cue bias explanation of the appearance studies. We conclude that a cue-bias explanation may operate with near-threshold and low-visibility stimuli, as was the case in Prinzmetal et al. (2008), but that such an explanation has no bearing on studies with suprathreshold stimuli. Consistent with our previous studies, the present data support the claim that attention does alter the contrast appearance of suprathreshold stimuli.

  20. Effects of quercetin on intracavernous pressure and expression of nitrogen synthase isoforms in arterial erectile dysfunction rat model

    PubMed Central

    Zhang, Yueyang; Huang, Changting; Liu, Shaoming; Bai, Jianqi; Fan, Xiaojing; Guo, Jun; Jia, Yingyu; Zhang, Zhijie; Chen, Xiaojun; Jia, Yusen; Zhang, Ping; Wang, Bin; Zhang, Xiuju

    2015-01-01

    Object: Oxidative stress involved in the regulation of arterial erectile dysfunction (A-ED). Previously report have indicated that quercetin have an antioxidant effect. In the current study, we have established the rats’ model for study the therapeutic effect of quercetin on A-ED and further investigated the molecular mechanism of action. Methods: Wistar rats were divided into sham group, A-ED group, A-ED group with low dose of quercetin, and A-ED group with high dose of quercetin. Intracavernous pressure (ICP) and mean arterial pressure (MBp) are two important indicators used for evaluation the A-ED. The changes of ICP and MBp were determined by cavernous nerve electrostimulation after treatment of quercetin at indicated doses. The expression of nitric oxide synthase (NOS) subtypes was detected by RT-PCR and Western blotting. Results: Our results indicated that ICP was significantly reduced in A-ED rats model compared with sham group, and was significantly increased after quercetin treatment (P < 0.01), while no significant effect on the MBp. The data also showed that sGC inhibitor ODQ and NOS inhibitor LNNA can significantly inhibited the ICP which induced by quercetin. These results suggest that NO-cGMP signaling pathway plays a crucial role in A-ED. Then, we found that the mRNA and protein levels of eNOS were significantly reduced in A-ED group compared with sham group. After treated with quercetin may cause the eNOS RNA and protein were significantly up-regulated (P < 0.01), showing a dose-dependent effect. iNOS expression have a certain degree of increased after quercetin treatment. nNOS expression was not significantly increased before and after treated with quercetin. In a word, quercetin can improved the A-ED by up-regulated ICP, which related to up-regulation of NO-cGMP signaling pathway. Conclusion: Preliminary results of this study suggested that quercetin protected expression and function of eNOS in cavernous endothelial cells, and restored part of

  1. Bioavailability of quercetin from its aglycone and its glucorhamnoside rutin in lactating dairy cows after intraduodenal administration.

    PubMed

    Gohlke, A; Ingelmann, C J; Nürnberg, G; Starke, A; Wolffram, S; Metges, C C

    2013-04-01

    Because of their health-promoting properties, flavonoids are used in feed supplements for ruminants, although scientific evidence for their efficacy in vivo is limited. It has been shown recently that bioavailability of quercetin is low after ruminal administration in cows because of degradation by the ruminal microbiota. It is unknown whether quercetin could be absorbed from the small intestine in ruminants if degradation is prevented; therefore, we investigated the bioavailability of quercetin after duodenal administration in 6 German Holstein cows. On 88 ± 3 d in milk, each cow received equivalent doses of quercetin [9, 18, or 27 mg of quercetin equivalents (QE)/kg of body weight] either as quercetin aglycone (QA) or as its glucorhamnoside rutin (RU). In addition, 2 control studies with duodenal administration of NaCl solution (0.9%) were conducted per cow to examine concentrations of flavonoids in plasma during regular feeding. Blood samples were collected at defined time intervals over a period of 24h before and after administration of the test compounds. A washout period of 2d was applied between the runs to avoid possible carryover effects. Concentrations of plasma quercetin aglycone and its metabolites isorhamnetin, tamarixetin, and kaempferol were measured after treatment with glucuronidase/sulfatase by HPLC with fluorescence detection. After administration of RU, levels of plasma quercetin did not increase above baseline, irrespective of dose administered. After duodenal administration of QA, the plasma concentration of QA and its methylated metabolites clearly increased above baseline. The maximal plasma concentrations of total flavonols (about 2h after application) increased in a dose-dependent manner but showed high interindividual variability (range 368.8 to 983.3 nmol/L at 27 mg of QE/kg of body weight) but peak time did not differ. Preadministration baseline values of total flavonols were reached again 3 to 4h after QA administration. The

  2. Quercetin modulates keratoconus metabolism in vitro

    PubMed Central

    McKay, Tina B; Sarker-Nag, Akhee; Lyon, Desiree’; Asara, John M; Karamichos, Dimitrios

    2016-01-01

    Corneal scarring is the result of a disease, infection or injury. The resulting scars cause significant loss of vision or even blindness. To-date, the most successful treatment is corneal transplantation, but it does not come without side effects. One of the corneal dystrophies that are correlated with corneal scarring is keratoconus (KC). The onset of the disease is still unknown; however, altered cellular metabolism has been linked to promoting the fibrotic phenotype and therefore scarring. We have previously shown that human keratoconus cells (HKCs) have altered metabolic activity when compared to normal human corneal fibroblasts (HCFs). In our current study, we present evidence that quercetin, a natural flavonoid, is a strong candidate for regulating metabolic activity of both HCFs and HKCs in vitro and therefore a potential therapeutic to target the altered cellular metabolism characteristic of HKCs. Targeted mass spectrometry-based metabolomics was performed on HCFs and HKCs with and without quercetin treatment in order to identify variations in metabolite flux. Overall, our study reveals a novel therapeutic target OF Quercetin on corneal stromal cell metabolism in both healthy and diseased states. Clearly, further studies are necessary in order to dissect the mechanism of action of quercetin. PMID:26173740

  3. Deglycosylation is a key step in biotransformation and lifespan effects of quercetin-3-O-glucoside in Caenorhabditis elegans.

    PubMed

    Dueñas, Montserrat; Surco-Laos, Felipe; González-Manzano, Susana; González-Paramás, Ana M; Gómez-Orte, Eva; Cabello, Juan; Santos-Buelga, Celestino

    2013-10-01

    Due to their purported healthful activities, quercetin and other flavonoids are being increasingly proposed as nutraceuticals. Quercetin occurs in food as glycosides; however, most assays on its activity have been performed with the aglycone, despite glycosylation deeply affects compound bioavailability. In this work, the uptake and lifespan effects of quercetin-3-O-glucoside (Q3Glc) and quercetin have been assessed in Caenorhabditis elegans. Q3Glc was taken up by this nematode in a concentration-dependent manner and rapidly deglycosylated to quercetin, which was accumulated in the worm and partially biotransformed to conjugated metabolites. Significant mean lifespan extension up to 23% compared to controls was observed in wild type worms cultivated in the presence of low concentrations of Q3Glc (10 μM and 25 μM), whereas exposure to greater concentrations of Q3Glc (50-200 μM) caused a reduction in mean and maximum lifespan compared with the control. By contrast, treatment of klo-1 and klo-2 mutant worms lacking β-glucosidase activity with 200 μM of Q3Glc led to extended mean lifespan (up to 39%), similar to quercetin aglycone at the same concentration levels. In those mutants, Q3Glc was accumulated without important deglycosylation to quercetin was produced. Taken together, these findings indicated that Q3Glc was taken up by the nematode in greater extent than quercetin, and that deglycosylation and subsequent aglycone accumulation in the worm appeared as key points to explain the observed lifespan effects. The obtained results also suggested that facilitated absorption should be more important for the uptake of quercetin derivatives than passive diffusion.

  4. Differential analysis of transient increases of serum cTnI in response to handling in rats.

    PubMed

    Mikaelian, Igor; Dunn, Michael E; Mould, Diane R; Hirkaler, Gerard; Geng, Wanping; Coluccio, Denise; Nicklaus, Rosemary; Singer, Thomas; Reddy, Micaela

    2013-12-01

    Serum cardiac troponins are the key biomarkers of myocardial necrosis in humans and in preclinical species. The use of ultrasensitive assays for serum cardiac troponin I (cTnI) as a biomarker in safety studies is hampered by interindividual differences. In this study, we investigated the effect of handling procedures on serum cTnI and explored modeling and simulation approaches to mitigate the impact of these interindividual differences. Femoral-catheterized male Crl:WI(Han) rats (n = 16/group) were left undisturbed in their cages with no handling; subjected to 5 min of isoflurane/O2 anesthesia (A); or placed into a rodent restrainer followed by simulated tail vein injection (RR). Serum cTnI concentrations were assessed over a 24-h period using an ultrasensitive assay, and the study was repeated for confirmation. The mean serum cTnI concentration pre-procedure was 4.2 pg/mL, and remained stable throughout the duration of the study in the rats submitted to the A procedure. Serum cTnI concentrations increased transiently after the RR procedure with a median time to maximum concentration (T max), of 1 and 2 h and a mean maximum value concentration (C max), of 53.0 and 7.2 pg/mL in the initial and repeat studies, respectively. A population pharmacodynamic model identified interindividual, procedure- and study-specific effects on serum cTnI concentrations in rats. It is concluded that a modeling and simulation approach more appropriately describes and statistically analyzes the data obtained with this ultrasensitive assays.

  5. Mesoporous silica as topical nanocarriers for quercetin: characterization and in vitro studies.

    PubMed

    Sapino, Simona; Ugazio, Elena; Gastaldi, Lucia; Miletto, Ivana; Berlier, Gloria; Zonari, Daniele; Oliaro-Bosso, Simonetta

    2015-01-01

    The flavonoid quercetin is extensively studied for its antioxidant and chemopreventive properties. However the poor water-solubility, low stability and short half-life could restrict its use in skin care products and therapy. The present study was aimed to evaluate the potential of aminopropyl functionalized mesoporous silica nanoparticles (NH2-MSN) as topical carrier system for quercetin delivery. Thermo gravimetric analysis, X-ray diffraction, high resolution transmission electron microscopy, nitrogen adsorption isotherms, FT-IR spectroscopy, zeta potential measurements and differential scanning calorimetry allowed analyzing with great detail the organic-inorganic molecular interaction. The protective effect of this vehicle on UV-induced degradation of the flavonoid was investigated revealing a certain positive influence of the inclusion on the photostability over time. Epidermal accumulation and transdermal permeation of this molecule were ex vivo evaluated using porcine skin mounted on Franz diffusion cells. The inclusion complexation with the inorganic nanoparticles increased the penetration of quercetin into the skin after 24h post-application without transdermal delivery. The effect of quercetin alone or given as complex with NH2-MSN on proliferation of JR8 human melanoma cells was evaluated by sulforhodamine B colorimetric proliferation assay. At a concentration 60 μM the complex with NH2-MSN was more effective than quercetin alone, causing about 50% inhibition of cell proliferation. PMID:25478737

  6. Quercetin Attenuates Chronic Ethanol-Induced Hepatic Mitochondrial Damage through Enhanced Mitophagy

    PubMed Central

    Yu, Xiao; Xu, Yanyan; Zhang, Shanshan; Sun, Jian; Liu, Peiyi; Xiao, Lin; Tang, Yuhan; Liu, Liegang; Yao, Ping

    2016-01-01

    Emerging evidence suggested mitophagy activation mitigates ethanol-induced liver injury. However, the effect of ethanol on mitophagy is inconsistent. Importantly, the understanding of mitophagy status after chronic ethanol consumption is limited. This study evaluated the effect of quercetin, a naturally-occurring flavonoid, on chronic ethanol-induced mitochondrial damage focused on mitophagy. An ethanol regime to mice for 15 weeks (accounting for 30% of total calories) led to significant mitochondrial damage as evidenced by changes of the mitochondrial ultrastructure, loss of mitochondrial membrane potential and remodeling of membrane lipid composition, which was greatly attenuated by quercetin (100 mg/kg.bw). Moreover, quercetin blocked chronic ethanol-induced mitophagy suppression as denoted by mitophagosomes-lysosome fusion and mitophagy-related regulator elements, including LC3II, Parkin, p62 and voltage-dependent anion channel 1 (VDAC1), paralleling with increased FoxO3a nuclear translocation. AMP-activated protein kinase (AMPK) and extracellular signal regulated kinase 2 (ERK2), instead of AKT and Sirtuin 1, were involved in quercetin-mediated mitophagy activation. Quercetin alleviated ethanol-elicited mitochondrial damage through enhancing mitophagy, highlighting a promising preventive strategy for alcoholic liver disease. PMID:26742072

  7. Quercetin-induced benzophenanthridine alkaloid production in suspension cell cultures of Sanguinaria canadensis.

    PubMed

    Mahady, G B; Beecher, C W

    1994-12-01

    Addition of micromolar concentrations of quercetin or rutin to suspension cell cultures of Sanguinaria canadensis L. (bloodroot) induced the biosynthesis of sanguinarine and chelerythrine in a dose-dependent manner. In contrast, related compounds: baicalein, naringin, naringenin, catechin, caffeic acid and benzoic acid displayed very weak inductive activity. Of the two active flavonoids, quercetin was the most effective for inducing benzophenanthridine alkaloid biosynthesis, with doses of 100 microM increasing alkaloid production over 375% as compared to negative controls. Quercetin's inductive effects were similar to that of an elicitor derived from fungus Penicillium expansum (PE-elicitor). Suppression of quercetin and PE-induced alkaloid biosynthesis by low doses of actinomycin D (5 micrograms/ml, alpha-amanitin (20 micrograms/ml), or cycloheximide (1 microgram/ml) demonstrate a requirement for both RNA and de novo cytoplasmic protein synthesis and suggest that alterations in gene expression are involved in the inductive mechanism. Furthermore, quercetin-induced alkaloid biosynthesis was significantly reduced by pretreatment of the cells with the calcium chelator, EGTA (3 mM), or the calcium channel inhibitor, verapamil (100 microM), suggesting that this process was calcium dependent.

  8. Quercetin ameliorates polychlorinated biphenyls-induced testicular DNA damage in rats.

    PubMed

    Lovato, F L; de Oliveira, C R; Adedara, I A; Barbisan, F; Moreira, K L S; Dalberto, M; da Rocha, M I U M; Marroni, N P; da Cruz, I B; Costabeber, I B

    2016-02-01

    Polychlorinated biphenyls (PCBs) are a group of environmental contaminants widely reported to cause gonadal toxicity in both humans and animals. This study investigated the amelioratory role of quercetin in PCBs-induced DNA damage in male Wistar rats. Polychlorinated biphenyls were administered intraperitoneally at a dose of 2 mg kg(-1) alone or in combination with quercetin (orally) at 50 mg kg(-1) for 25 days. Quercetin modulation of PCBs-induced gonadal toxicity was evaluated using selected oxidative stress indices, comet assay, measurement of DNA concentration and histology of the testes. Administration of PCBs alone caused a significant (P < 0.05) depletion in the total thiol level in testes of treated rats. Conversely, the levels of reactive oxygen species (ROS) and thiobarbituric acid reactive substances (TBARS) production were markedly elevated in testes of PCBs-treated rats compared with control. Further, PCBs exposure produced statistically significant increases in DNA tail migration, degraded double-stranded DNA (dsDNA) concentration and histological alterations of testes of the treated rats compared to control. Quercetin cotreatment significantly improved the testicular antioxidant status, decreased DNA fragmentation and restored the testicular histology, thus demonstrating the protective effect of quercetin in PCBs-treated rats.

  9. Mesoporous silica as topical nanocarriers for quercetin: characterization and in vitro studies.

    PubMed

    Sapino, Simona; Ugazio, Elena; Gastaldi, Lucia; Miletto, Ivana; Berlier, Gloria; Zonari, Daniele; Oliaro-Bosso, Simonetta

    2015-01-01

    The flavonoid quercetin is extensively studied for its antioxidant and chemopreventive properties. However the poor water-solubility, low stability and short half-life could restrict its use in skin care products and therapy. The present study was aimed to evaluate the potential of aminopropyl functionalized mesoporous silica nanoparticles (NH2-MSN) as topical carrier system for quercetin delivery. Thermo gravimetric analysis, X-ray diffraction, high resolution transmission electron microscopy, nitrogen adsorption isotherms, FT-IR spectroscopy, zeta potential measurements and differential scanning calorimetry allowed analyzing with great detail the organic-inorganic molecular interaction. The protective effect of this vehicle on UV-induced degradation of the flavonoid was investigated revealing a certain positive influence of the inclusion on the photostability over time. Epidermal accumulation and transdermal permeation of this molecule were ex vivo evaluated using porcine skin mounted on Franz diffusion cells. The inclusion complexation with the inorganic nanoparticles increased the penetration of quercetin into the skin after 24h post-application without transdermal delivery. The effect of quercetin alone or given as complex with NH2-MSN on proliferation of JR8 human melanoma cells was evaluated by sulforhodamine B colorimetric proliferation assay. At a concentration 60 μM the complex with NH2-MSN was more effective than quercetin alone, causing about 50% inhibition of cell proliferation.

  10. Transient increases in choroidal thickness are consistently associated with brief daily visual stimuli that inhibit ocular growth in chicks.

    PubMed

    Nickla, Debora L

    2007-05-01

    comparisons). In all the effect was axial with growth rate being significantly inhibited. In all cases the choroids showed significant transient increases in thickness as well. Form deprivation: vision or strobe vs control: 58 and 15 vs -3 microm. Negative lenses: vision or strobe vs controls: 74 and 17 vs -17 microm. Dark: vision or myopic defocus vs control: 56 and 46 vs 11 microm. Dark: frequent vs control: 103 vs 5 microm. In the "infrequent myopic defocus" condition eyes did not compensate to the defocus, however they did not become myopic. The choroidal response was not significant. These results support the hypothesis that these brief choroidal responses may play a role in ocular growth inhibition.

  11. Effect of quercetin supplementation on lung antioxidants after experimental influenza virus infection.

    PubMed

    Kumar, Pankaj; Khanna, Madhu; Srivastava, Vikram; Tyagi, Yogesh Kumar; Raj, Hanumanthrao G; Ravi, K

    2005-06-01

    In the mice, instillation of influenza virus A/Udorn/317/72(H3N2) intranasally resulted in a significant decrease in the pulmonary concentrations of catalase, reduced glutathione, and superoxide dismutase. There was a decrease in vitamin E level also. These effects were observed on the 5th day after viral instillation. Oral supplementation with quercetin simultaneous with viral instillation produced significant increases in the pulmonary concentrations of catalase, reduced glutathione, and superoxide dismutase. However, quercetin did not reverse the fall in vitamin E level associated with the viral infection. It is concluded that during influenza virus infection, there is "oxidative stress." Because quercetin restored the concentrations of many antioxidants, it is proposed that it may be useful as a drug in protecting the lung from the deleterious effects of oxygen derived free radicals released during influenza virus infection.

  12. Essential role of Nrf2 in keratinocyte protection from UVA by quercetin

    SciTech Connect

    Kimura, Shintarou; Warabi, Eiji; Yanagawa, Toru; Ma, Dongmei; Itoh, Ken; Ishii, Yoshiyuki; Kawachi, Yasuhiro; Ishii, Tetsuro

    2009-09-11

    Much of the cell injury caused by ultraviolet A (UVA) irradiation is associated with oxidative stress. Quercetin is a major natural polyphenol that is known to protect cells from UVA-induced damage. Here, we investigated the molecular mechanism of this protection. Quercetin pretreatment strongly suppressed UVA-induced apoptosis in human keratinocyte HaCaT cells, markedly increased protein levels of the transcription factor Nrf2, induced the expression of antioxidative genes, and dramatically reduced the production of reactive oxygen species following UVA irradiation. Importantly, these beneficial effects were greatly attenuated by downregulating Nrf2 expression. Thus, quercetin protects cells from UVA damage mainly by elevating intracellular antioxidative activity via the enhanced accumulation of a transcription factor for antioxidant genes, Nrf2.

  13. Solid dispersion of quercetin in cellulose derivative matrices influences both solubility and stability.

    PubMed

    Li, Bin; Konecke, Stephanie; Harich, Kim; Wegiel, Lindsay; Taylor, Lynne S; Edgar, Kevin J

    2013-02-15

    Amorphous solid dispersions (ASD) of quercetin (Que) in cellulose derivative matrices, carboxymethylcellulose acetate butyrate (CMCAB), hydroxypropylmethylcellulose acetate succinate (HPMCAS), and cellulose acetate adipate propionate (CAAdP) were prepared with the goal of identifying an ASD that effectively increased Que aqueous solution concentration. Crystalline quercetin and Que/poly(vinylpyrrolidinone) (PVP) ASD were evaluated for comparison. Powder X-ray diffraction (XRPD) and differential scanning calorimetry (DSC) were used to examine the crystallinity of ASDs, physical mixtures (PM) and quercetin. ASDs were amorphous up to 50 wt% Que. Que stability against crystallization and solution concentrations from these ASDs were significantly higher than those observed for physical mixtures and crystalline Que. PVP stabilizes against both Que degradation and recrystallization; in contrast, these carboxylated cellulose derivatives inhibit recrystallization but release Que slowly. PVP ASDs afforded fast and complete drug release, while ASDs using these three cellulose derivatives provide slow, incomplete, pH-triggered drug release. PMID:23399255

  14. Quercetin suppresses immune cell accumulation and improves mitochondrial gene expression in adipose tissue of diet‐induced obese mice

    PubMed Central

    Takahashi, Yumiko; Sakurai, Mutsumi; Akimoto, Yukari; Tsushida, Tojiro; Oike, Hideaki; Ippoushi, Katsunari

    2015-01-01

    Scope To examine the effect of dietary quercetin on the function of epididymal adipose tissue (EAT) in Western diet‐induced obese mice. Methods and results C57BL/6J mice were fed a control diet; a Western diet high in fat, cholesterol, and sucrose; or the same Western diet containing 0.05% quercetin for 18 weeks. Supplementation with quercetin suppressed the increase in the number of macrophages, the decrease in the ratio of CD4+ to CD8+ T cells in EAT, and the elevation of plasma leptin and tumor necrosis factor α levels in mice fed the Western diet. Comprehensive gene expression analysis revealed that quercetin suppressed gene expression associated with the accumulation and activation of immune cells, including macrophages and lymphocytes in EAT. It also improved the expression of the oxidative stress‐sensitive transcription factor NFκB, NADPH oxidases, and antioxidant enzymes. Quercetin markedly increased gene expression associated with mitochondrial oxidative phosphorylation and mitochondrial DNA content. Conclusion Quercetin most likely universally suppresses the accumulation and activation of immune cells, including antiinflammatory cells, whereas it specifically increased gene expression associated with mitochondrial oxidative phosphorylation. Suppression of oxidative stress and NFκB activity likely contributed to the prevention of the accumulation and activation of immune cells and resulting chronic inflammation. PMID:26499876

  15. Quercetin protects human brain microvascular endothelial cells from fibrillar β-amyloid1–40-induced toxicity

    PubMed Central

    Li, Yongjie; Zhou, Sibai; Li, Jinze; Sun, Yuhua; Hasimu, Hamlati; Liu, Rui; Zhang, Tiantai

    2015-01-01

    Amyloid beta-peptides (Aβ) are known to undergo active transport across the blood-brain barrier, and cerebral amyloid angiopathy has been shown to be a prominent feature in the majority of Alzheimer׳s disease. Quercetin is a natural flavonoid molecule and has been demonstrated to have potent neuroprotective effects, but its protective effect on endothelial cells under Aβ-damaged condition is unclear. In the present study, the protective effects of quercetin on brain microvascular endothelial cells injured by fibrillar Aβ1–40 (fAβ1–40) were observed. The results show that fAβ1–40-induced cytotoxicity in human brain microvascular endothelial cells (hBMECs) can be relieved by quercetin treatment. Quercetin increases cell viability, reduces the release of lactate dehydrogenase, and relieves nuclear condensation. Quercetin also alleviates intracellular reactive oxygen species generation and increases superoxide dismutase activity. Moreover, it strengthens the barrier integrity through the preservation of the transendothelial electrical resistance value, the relief of aggravated permeability, and the increase of characteristic enzyme levels after being exposed to fAβ1–40. In conclusion, quercetin protects hBMECs from fAβ1–40-induced toxicity. PMID:26579424

  16. Chromatographic separation and concentration of quercetin and (+)-catechin using mesoporous composites based on MCM-41

    NASA Astrophysics Data System (ADS)

    Karpov, S. I.; Belanova, N. A.; Korabel'nikova, E. O.; Nedosekina, I. V.; Roessner, F.; Selemenev, V. F.

    2015-05-01

    Data on chromatographic separation of quercetin and (+)-catechin-flavonoids with similar physicochemical (including sorption) properties—are presented. The highest efficiency of chromatographic process at high sorption capacity of the material with respect to quercetin and slightly lower capacity for (+)-catechin were observed when silylated composites of ordered MCM-41 type materials were used. The application of acetonitrile as a solvent increased the sorption capacity of the material and can be recommended for separation of related polyphenol substances and their determination using ordered MCM-41 modified with trimethylchlorosilane as a stationary phase in a chromatographic column.

  17. Transient feeding of a concentrate-rich diet increases the severity of subacute ruminal acidosis in dairy cattle.

    PubMed

    Pourazad, P; Khiaosa-Ard, R; Qumar, M; Wetzels, S U; Klevenhusen, F; Metzler-Zebeli, B U; Zebeli, Q

    2016-02-01

    The objective of this study was to investigate the effect of the pattern of concentrate-rich feeding on subacute ruminal acidosis (SARA), its severity, and the corresponding changes in VFA concentration. Eight rumen-cannulated Holstein cows were assigned to a 2 × 2 crossover design with 2 SARA challenge models and 2 experimental runs ( = 8 per treatment). Each run lasted for 40 d, consisting of a 6-d baseline, a 6-d gradual grain adaptation, and a 28-d SARA challenge period. The 2 SARA challenge models were transient (TRA) and persistent (PER) SARA. Initially, all cows were subjected to a forage-only diet (baseline) and gradually switched to 60% concentrate (DM basis). Then, cows in the PER model were continuously challenged for 28 d, whereas cows in the TRA model had a 7-d break from the SARA diet and were fed the forage-only diet after the first 7 d of SARA challenge. Thereafter, the TRA cows were rechallenged with the SARA diet. Wireless ruminal pH sensors were used to obtain ruminal pH profiles and temperature over the experimental period. For the determination of VFA, free ruminal liquid (FRL) and particle-associated ruminal liquid (PARL) were collected once for the baseline and twice (d 20 and 40 for the PER model) or 3 times (d 13, 30, and 40 for the TRA model) during SARA, each time at 0, 4, and 8 h after the morning feeding. Cows in both models experienced SARA albeit with day-to-day variation. From the start until the first 7-d SARA, cows of both models had similar pH profiles, but during the rechallenge, SARA was more severe in the TRA model than in the PER model based on lower daily mean ruminal pH (5.93 vs. 6.15; SEM 0.058) and double the amount of time at pH < 5.8 (497 vs. 278 min; SEM 68.61, < 0.05). Mean ruminal temperature was raised during SARA compared with the baseline (38.9 vs. 38.7°C; SEM 0.057, < 0.001). Concentrations of VFA increased with increasing time after feeding ( < 0.001). In general, SARA challenge (d 40 vs. the baseline), but not

  18. Effects of quercetin, a natural phenolic compound, in the differentiation of human mesenchymal stem cells (MSC) into adipocytes and osteoblasts.

    PubMed

    Casado-Díaz, Antonio; Anter, Jaouad; Dorado, Gabriel; Quesada-Gómez, José Manuel

    2016-06-01

    Natural phenols may have beneficial properties against oxidative stress, which is associated with aging and major chronic aging-related diseases, such as loss of bone mineral mass (osteoporosis) and diabetes. The main aim of this study was to analyze the effect of quercetin, a major nutraceutical compound present in the "Mediterranean diet", on mesenchymal stem-cell (MSC) differentiation. Such cells were induced to differentiate into osteoblasts or adipocytes in the presence of two quercetin concentrations (0.1 and 10μM). Several physiological parameters and the expression of osteoblastogenesis and adipogenesis marker genes were monitored. Quercetin (10μM) inhibited cell proliferation, alkaline phosphatase (ALPL) activity and mineralization, down-regulating the expression of ALPL, collagen type I alpha 1 (COL1A1) and osteocalcin [bone gamma-carboxyglutamate protein (BGLAP)] osteoblastogenesis-related genes in MSC differentiating into osteoblasts. Moreover, in these cultures, CCAAT/enhancer-binding protein alpha (CEBPA) and peroxisome proliferator-activated receptor gamma 2 (PPARG2) adipogenic genes were induced, and cells differentiated into adipocytes were observed. Quercetin did not affect proliferation, but increased adipogenesis, mainly at 10-μM concentration in MSC induced to differentiate to adipocytes. β- and γ-catenin (plakoglobin) nuclear levels were reduced and increased, respectively, in quercetin-treated cultures. This suggests that the effect of high concentration of quercetin on MSC osteoblastic and adipogenic differentiation is mediated via Wnt/β-catenin inhibition. In conclusion, quercetin supplementation inhibited osteoblastic differentiation and promoted adipogenesis at the highest tested concentration. Such possible adverse effects of high quercetin concentrations should be taken into account in nutraceutical or pharmaceutical strategies using such flavonol. PMID:27142748

  19. Quercetin Modulates the Effects of Chromium Exposure on Learning, Memory and Antioxidant Enzyme Activity in F1 Generation Mice.

    PubMed

    Halder, Sumita; Kar, Rajarshi; Mehta, Ashish K; Bhattacharya, Swapan K; Mediratta, Pramod K; Banerjee, Basu D

    2016-06-01

    In the present study, we investigated whether chromium (Cr) administered to the dams (F0) during lactation period could affect memory and oxidative stress in F1 generation mice in their adulthood and whether quercetin could modulate these effects. Morris water maze (MWM) was used to test for spatial memory. Passive avoidance task and elevated plus maze were used to test for acquisition and retention memory. Oxidative stress was evaluated by measuring glutathione-S-transferase (GST), catalase activity and malonaldehyde (MDA) levels in the brain tissue. The results of MWM showed that the animals in the Cr-treated group compared to control have better spatial memory that was further enhanced when Cr was administered along with quercetin (50 mg/kg). The elevated plus maze test also showed the Cr-treated group to improve acquisition as well as retention memory compared to control. Co-treatment with quercetin (all doses) also exhibited enhanced acquisition and retention memory compared to control. The passive avoidance task demonstrated no significant improvement in memory in the Cr-treated mice but co-treatment with quercetin (100 mg/kg) showed improved acquisition memory compared to control which was significantly better than the animals treated with chromium alone. GST activity was significantly increased in the Cr-treated animals, and this was further increased in groups treated with Cr and quercetin (all doses). Chromium when administered alone and in combination with quercetin (all doses) significantly reduced MDA levels. However, Cr treatment did not show significant change in catalase activity. Nevertheless, co-treatment with quercetin (25 and 50 mg/kg) resulted in significant decrease in catalase activity. Thus, our study demonstrates that Cr exposure during lactation could be beneficial for pups with respect to augmentation of cognitive function and reduction of oxidative stress. Quercetin could probably enhance this effect to some extent.

  20. Red wine alcohol promotes quercetin absorption and directs its metabolism towards isorhamnetin and tamarixetin in rat intestine in vitro

    PubMed Central

    Dragoni, Stefania; Gee, Jennifer; Bennett, Richard; Valoti, Massimo; Sgaragli, Giampietro

    2006-01-01

    Moderate consumption of red wine has been associated with beneficial effects on human health, and this has been attributed to the flavonoid content. Factors that influence the bioavailability of this group of polyphenolic compounds are therefore important. Using the rat cannulated everted jejunal sac technique, we have investigated the effect of alcohol on the intestinal absorption of quercetin and its 3-O-glucoside from red wine. Tissue preparations were incubated in whole or dealcoholised red wine, diluted 1 : 1 with Krebs buffer for 20 min at 37°C, after which the mucosa was removed and processed for HPLC analysis. Tissues exposed to red wine had significantly higher amounts of both quercetin (× 3; P<0.001) and quercetin-3-O-glucoside (× 1.5; P<0.01) associated with them, compared with sacs incubated in the dealcoholised equivalent. In addition, both tamarixetin (T) and isorhamnetin (I), in the mucosal tissue from sacs exposed to the whole wine, were significantly elevated approximately two fold (P<0.05; P<0.01, respectively). Similar results were obtained when sacs were incubated in Krebs buffer containing a mixture of pure quercetin and quercetin-3-O-glucoside with or without alcohol, and, although effects on the apparent absorption of Q and Q-3-G were not so marked, concentrations of the metabolites quercetin-3-O-glucuronide and I were significantly increased by the presence of alcohol (P<0.01 and P<0.001, respectively). It is therefore plausible that the moderate alcohol content of red wine contributes to its beneficial health effects in humans by both increasing the absorption of quercetin and quercetin-3-O-glucoside and by channelling their metabolism towards O-methylation to yield compounds (T and I), which have potential protective effects against cancer and cardiovascular diseases. PMID:16444288

  1. Quercetin Modulates the Effects of Chromium Exposure on Learning, Memory and Antioxidant Enzyme Activity in F1 Generation Mice.

    PubMed

    Halder, Sumita; Kar, Rajarshi; Mehta, Ashish K; Bhattacharya, Swapan K; Mediratta, Pramod K; Banerjee, Basu D

    2016-06-01

    In the present study, we investigated whether chromium (Cr) administered to the dams (F0) during lactation period could affect memory and oxidative stress in F1 generation mice in their adulthood and whether quercetin could modulate these effects. Morris water maze (MWM) was used to test for spatial memory. Passive avoidance task and elevated plus maze were used to test for acquisition and retention memory. Oxidative stress was evaluated by measuring glutathione-S-transferase (GST), catalase activity and malonaldehyde (MDA) levels in the brain tissue. The results of MWM showed that the animals in the Cr-treated group compared to control have better spatial memory that was further enhanced when Cr was administered along with quercetin (50 mg/kg). The elevated plus maze test also showed the Cr-treated group to improve acquisition as well as retention memory compared to control. Co-treatment with quercetin (all doses) also exhibited enhanced acquisition and retention memory compared to control. The passive avoidance task demonstrated no significant improvement in memory in the Cr-treated mice but co-treatment with quercetin (100 mg/kg) showed improved acquisition memory compared to control which was significantly better than the animals treated with chromium alone. GST activity was significantly increased in the Cr-treated animals, and this was further increased in groups treated with Cr and quercetin (all doses). Chromium when administered alone and in combination with quercetin (all doses) significantly reduced MDA levels. However, Cr treatment did not show significant change in catalase activity. Nevertheless, co-treatment with quercetin (25 and 50 mg/kg) resulted in significant decrease in catalase activity. Thus, our study demonstrates that Cr exposure during lactation could be beneficial for pups with respect to augmentation of cognitive function and reduction of oxidative stress. Quercetin could probably enhance this effect to some extent. PMID:26521059

  2. Protective effect of quercetin on pig intestinal integrity after transport stress is associated with regulation oxidative status and inflammation

    PubMed Central

    ZOU, Yi; WEI, Hong Kui; XIANG, Quan-Hang; WANG, Jun; ZHOU, Yuan-Fei; PENG, Jian

    2016-01-01

    This experiment was conducted to evaluate the effects of quercetin supplementation on intestinal integrity, intestinal reactive oxygen species (ROS) levels and intestinal inflammation in pigs under transport stress. A total of 170 finishing pigs were randomly assigned into two groups. Animals in the control group consumed a basal diet, while those in the treatment group consumed the same diet supplemented with 25 mg quercetin per kg feed. After a 4-week period, pigs were transported for 5 hr. The quercetin-supplemented pigs showed decreased serum levels of endotoxin (P<0.05), increased height of jejunum villi (P<0.05), and increased occludin and zonula occudens-1 (ZO-1) mRNA expression in the jejunum (P<0.05). These parameters are associated with intestinal health and were markedly improved by quercetin supplementation. Pigs consuming the quercetin-supplemented diet had lower intestinal levels of ROS and malondialdehyde (MDA) compared with the control group (P<0.05). This finding coincided with greater inhibition of the innate immune system (P<0.05), including mitogen-activated protein kinase (MAPK), protein kinase B (Akt) and nuclear factor κB (NF-κB) signaling pathways, as well as decreased expression of inflammatory cytokines in the jejunum. These results indicate that quercetin alleviates intestinal injury in pigs during transport, probably through modulation of intestinal oxidative status and inflammation. PMID:27301842

  3. Amelioration of intracellular stress and reduction of neural tube defects in embryos of diabetic mice by phytochemical quercetin

    PubMed Central

    Cao, Lixue; Tan, Chengyu; Meng, Fantong; Liu, Peiyan; Reece, E. Albert; Zhao, Zhiyong

    2016-01-01

    Diabetes mellitus in early pregnancy causes birth defects, including neural tube defects (NTDs). Hyperglycemia increases production of nitric oxide (NO) through NO synthase 2 (Nos2) and reactive oxygen species (ROS), generating nitrosative and oxidative stress conditions in the embryo. The present study aimed to target nitrosative stress using a naturally occurring Nos2 inhibitor, quercetin, to prevent NTDs in the embryos of diabetic mice. Daily administration of quercetin to diabetic pregnant mice during the hyperglycemia-susceptible period of organogenesis significantly reduced NTDs and cell apoptosis in the embryos, compared with those of vehicle-treated diabetic pregnant mice. Using HPLC-coupled ESI-MS/MS, quercetin metabolites, including methylated and sulfonylated derivatives, were detected in the conceptuses. The methylated metabolite, 3-O-methylquercetin, was shown to reduce ROS level in embryonic stem cells cultured in high glucose. Quercetin treatment decreased the levels of Nos2 expression, protein nitrosylation, and protein nitration, alleviating nitrosative stress. Quercetin increased the expression of superoxide dismutase 1 and 2, and reduced the levels of oxidative stress markers. Expression of genes of redox regulating enzymes and DNA damage repair factors was upregulated. Our study demonstrates that quercetin ameliorates intracellular stresses, regulates gene expression, and reduces embryonic malformations in diabetic pregnancy. PMID:26887929

  4. Quercetin conjugated superparamagnetic magnetite nanoparticles for in-vitro analysis of breast cancer cell lines for chemotherapy applications.

    PubMed

    Kumar, S Rajesh; Priyatharshni, S; Babu, V N; Mangalaraj, D; Viswanathan, C; Kannan, S; Ponpandian, N

    2014-12-15

    The magnetic nanoparticles attract increasing interest due to their opportunities in cancer therapy and used as drug carriers for several other diseases. The present study investigates the quercetin conjugated superparamagnetic Fe3O4 nanoparticles for in-vitro analysis of breast cancer cell lines for chemotherapy. A simple precipitation method was used to prepare the dextran coated Fe3O4 nanoparticles and the anticancer flavonoid quercetin was conjugated on the surface via carboxylic/amine group using nanoprecipitation method. The structural, morphological and the magnetic properties of the prepared materials were studied by using X-ray diffractometer (XRD), Fourier transformed infer-red spectrometer (FTIR), transmission electron microscope (TEM) and vibrating sample magnetometer (VSM). The MTT (3-(4,5-dimethylthiahiazol-2-yl)-2,5-diphenyl tetrazolium) assay of dextran coated Fe3O4 nanoparticles did not exhibit notable toxicity against MCF7 cells, whereas the cytotoxicity of quercetin conjugated Fe3O4 nanoparticles increased significantly in comparison with pure quercetin. The incubation of MCF-7 cells with quercetin conjugated Fe3O4 nanoparticles (QCMNPs) shows significant changes in cellular morphology observed through fluorescent microscopy. The results validate the prepared quercetin conjugated Fe3O4 nanoparticles are promising anticancer agents for targeted drug delivery. PMID:25278361

  5. Quercetin conjugated superparamagnetic magnetite nanoparticles for in-vitro analysis of breast cancer cell lines for chemotherapy applications.

    PubMed

    Kumar, S Rajesh; Priyatharshni, S; Babu, V N; Mangalaraj, D; Viswanathan, C; Kannan, S; Ponpandian, N

    2014-12-15

    The magnetic nanoparticles attract increasing interest due to their opportunities in cancer therapy and used as drug carriers for several other diseases. The present study investigates the quercetin conjugated superparamagnetic Fe3O4 nanoparticles for in-vitro analysis of breast cancer cell lines for chemotherapy. A simple precipitation method was used to prepare the dextran coated Fe3O4 nanoparticles and the anticancer flavonoid quercetin was conjugated on the surface via carboxylic/amine group using nanoprecipitation method. The structural, morphological and the magnetic properties of the prepared materials were studied by using X-ray diffractometer (XRD), Fourier transformed infer-red spectrometer (FTIR), transmission electron microscope (TEM) and vibrating sample magnetometer (VSM). The MTT (3-(4,5-dimethylthiahiazol-2-yl)-2,5-diphenyl tetrazolium) assay of dextran coated Fe3O4 nanoparticles did not exhibit notable toxicity against MCF7 cells, whereas the cytotoxicity of quercetin conjugated Fe3O4 nanoparticles increased significantly in comparison with pure quercetin. The incubation of MCF-7 cells with quercetin conjugated Fe3O4 nanoparticles (QCMNPs) shows significant changes in cellular morphology observed through fluorescent microscopy. The results validate the prepared quercetin conjugated Fe3O4 nanoparticles are promising anticancer agents for targeted drug delivery.

  6. Quercetin relieves chronic lead exposure-induced impairment of synaptic plasticity in rat dentate gyrus in vivo.

    PubMed

    Hu, Pu; Wang, Ming; Chen, Wei-Heng; Liu, Ji; Chen, Liang; Yin, Shu-Ting; Yong, Wu; Chen, Ju-Tao; Wang, Hui-Li; Ruan, Di-Yun

    2008-07-01

    Increasing evidence suggests that lead (Pb) produces impairments partly through oxidative stress. Though many researchers have investigated protective effect of some antioxidant nutrients against Pb toxicity, little information is available about the effect of antioxidants on Pb-induced impairment of synaptic plasticity. Quercetin, a strong antioxidant and radical scavenger, is the representative natural flavonoid molecule abundant in fruits and vegetables. Previous studies have found that quercetin was neuroprotective in many cases. This study was designed to evaluate the effect of quercetin on chronic Pb exposure-induced impairment of synaptic plasticity in adult rat dentate gyrus (DG) area in vivo. The input/output (I/O) functions, paired-pulse reactions (PPR), excitatory postsynaptic potential (EPSP), and population spike (PS) amplitude were measured in the DG area of different groups of rats in response to stimulation applied to the lateral perforant path. The results showed that the depressed I/O, PPR, and long-term potentiation (LTP) of Pb-exposed group were significantly increased by quercetin treatment. In addition, hippocampal Pb concentration was partially reduced after quercetin treatment. These findings suggest that quercetin treatment could relieve chronic Pb exposure-induced impairment of synaptic plasticity and might be a potential therapeutic intervention to cure cognitive deficits induced by Pb.

  7. Quercetin, an in vitro inhibitor of CYP3A, does not contribute to the interaction between nifedipine and grapefruit juice.

    PubMed Central

    Rashid, J; McKinstry, C; Renwick, A G; Dirnhuber, M; Waller, D G; George, C F

    1993-01-01

    Quercetin, a flavonoid present in various fruits, is a potent in vitro inhibitor of CYP3A. Its role in the reported interaction between grapefruit juice and nifedipine has been determined in vivo in humans. Eight healthy volunteers were given in random order 10 mg nifedipine orally, either alone or with 200 ml double strength grapefruit juice, or with 400 mg quercetin. The area under the plasma concentration-time curve (AUC) for nifedipine with grapefruit juice (mean 320 ng ml(-1) h) was increased significantly (P < 0.01) compared with the AUC when nifedipine was given alone (mean 218 ng ml(-1) h). The time to peak plasma concentration for nifedipine with grapefruit juice (1.5 h) was also increased (P < 0.05) compared with control (0.5 h) suggesting delayed absorption. Although quercetin delayed the time to peak nifedipine concentration (1.3 h) it did not alter the AUC of either the parent drug (mean 209 ng ml(-1) h) or its first-pass metabolite. The results suggest that quercetin does not contribute to the effects of grapefruit juice (which contains <10 mg of quercetin 200 ml(-1)) on the metabolism of nifedipine. Oral doses of quercetin, similar to those possible from the ingestion of other fruits such as strawberries, do not produce in vivo inhibition of CYP3A mediated metabolism of nifedipine. PMID:12959295

  8. Electrospun quercetin-loaded zein nanoribbons.

    PubMed

    Li, Xiao-Yan; Shi, Chen-Jie; Yu, Deng-Guang; Liao, Yao-Zu; Wang, Xia

    2014-01-01

    This study investigates quercetin-loaded zein nanoribbons, which were fabricated using different types of electrospinning processes. Using ethanol aqueous solutions as sheath fluids, the widths of quercetin-loaded zein nanoribbons (D, nm) could be manipulated simply through the adjustment of water contents(C) in the sheath fluids according to an equation of D=958-8.01C(r=0.9977), as indicated by the field emission scanning electron microscopic observations. X-ray diffraction and attenuated total reflectance Fourier transform infrared analysis suggested that the quercetin presented in the zein nanoribbons in an amorphous state due to their high compability resulted from hydrogen bonds. In vitro dissolution tests verified that nanoribbons from the coaxial process and single fluid process could provide drug sustained release profiles via a typical Fickian diffusion mechanism, and the former exhibited better performance than the later in terms of small initial burst effect and leveling-off release. Coaxial electrospinning with solvents can expand the capability of electrospinning in generating nanoproducts and provide a way for improving the nanoproducts' quality and functional performance. PMID:25226898

  9. Chronic administration of quercetin prevent spatial learning and memory deficits provoked by chronic stress in rats.

    PubMed

    Mohammadi, Hadis Said; Goudarzi, Iran; Lashkarbolouki, Taghi; Abrari, Kataneh; Elahdadi Salmani, Mahmoud

    2014-08-15

    There are several reports that cognitive impairment is observed in stress related disorders and chronic stress impairs learning and memory. However, very few studies have looked into the possible ways of preventing this stress-induced deficit. This research study was conducted to evaluate the effects of quercetin, a natural flavonoid, with strong antioxidant and free radical scavenger properties, on chronic stress induced learning and memory deficits and oxidative stress in hippocampus. For chronic stress, rats were restrained daily for 6h/day (from 9:00 to 15:00) for 21 days in well-ventilated plexiglass tubes without access to food and water. The animals were injected with quercetin or vehicle 60 min before restraint stress over a period of 21 days. Then, rats trained with six trials per day for 6 consecutive days in the water maze. On day 28, a probe test was done to measure memory retention. In addition, oxidative stress markers in the hippocampus were evaluated. Results of this study demonstrated that chronic stress exposure rats exhibited higher escape latency during training trials and reduced time spent in target quadrant, higher escape location latency and average proximity in probe trial test. Quercetin (50mg/kg) treatment during restraint stress (21 days) markedly decreased escape latency and increased time spent in target quadrant during Morris water maze task. In comparison to vehicle treated group, chronic-stress group had significantly higher malondialdehyde (MDA) levels, significantly higher superoxide dismutase (SOD) activity and significantly lower glutathione peroxidase (GPx) activity in the hippocampus. Quercetin treatment caused a significant decrease in the hippocampus MDA levels and improves SOD and GPx activities in stressed animals. Finally, quercetin significantly decreased plasma corticosterone levels in stressed animals. Based on results of this study, chronic stress has detrimental effects on learning and memory and quercetin treatment

  10. The Effect of Quercetin on Plasma Oxidative Status, C-Reactive Protein and Blood Pressure in Women with Rheumatoid Arthritis

    PubMed Central

    Javadi, Fatemeh; Eghtesadi, Shahryar; Ahmadzadeh, Arman; Aryaeian, Naheed; Zabihiyeganeh, Mozhdeh; Foroushani, Abbas Rahimi; Jazayeri, Shima

    2014-01-01

    Background: Considering the increased production of free radicals and inflammatory factors in rheumatoid arthritis (RA) and the effects of bioflavonoid quercetin on reducing oxidative stress, inflammation and blood pressure, the present study examined the effects of bioflavonoid quercetin on total antioxidant capacity (TAC) of plasma, lipid peroxidation and blood pressure in women with RA. Methods: The current study was a randomized double-blind clinical trial in which 51 women with RA aged 19-70 years, were participated. Patients were assigned into quercetin (500 mg/day) or placebo groups for 8 weeks. Dietary intake was recorded using 24-h dietary recall questionnaire and the physical activity was assessed through an international short questionnaire of physical activity at the beginning and end of the study. Plasma TAC and malondialdehyde (MDA) using colorimetric method, oxidized low density lipoprotein (ox-LDL) and high sensitivity C-reactive protein (hs-CRP) using enzyme-linked immunosorbent assay method and also blood pressure were measured at the beginning and end of intervention. Results: After 8 weeks there were no significant differences in TAC of plasma, ox-LDL, MDA, hs-CRP, systolic and diastolic blood pressure between quercetin and placebo groups and in each group comparing before and after. Conclusions: In this study, quercetin had no effect on oxidative and inflammatory status of plasma and blood pressure in patients with RA. Further studies are needed to ensure the effect of quercetin on oxidative stress and inflammation in human. PMID:24829713

  11. Quercetin decreases high-fat diet induced body weight gain and accumulation of hepatic and circulating lipids in mice.

    PubMed

    Hoek-van den Hil, E F; van Schothorst, E M; van der Stelt, I; Swarts, H J M; Venema, D; Sailer, M; Vervoort, J J M; Hollman, P C H; Rietjens, I M C M; Keijer, J

    2014-09-01

    Dietary flavonoids may protect against cardiovascular diseases (CVD). Increased circulating lipid levels and hepatic lipid accumulation are known risk factors for CVD. The aim of this study was to investigate the effects and underlying molecular mechanisms of the flavonoid quercetin on hepatic lipid metabolism in mice with high-fat diet induced body weight gain and hepatic lipid accumulation. Adult male mice received a 40 energy% high-fat diet without or with supplementation of 0.33 % (w/w) quercetin for 12 weeks. Body weight gain was 29 % lower in quercetin fed mice (p < 0.01), while the energy intake was not significantly different. Quercetin supplementation lowered hepatic lipid accumulation to 29 % of the amount present in the control mice (p < 0.01). (1)H nuclear magnetic resonance serum lipid profiling revealed that the supplementation significantly lowered serum lipid levels. Global gene expression profiling of liver showed that cytochrome P450 2b (Cyp2b) genes, key target genes of the transcription factor constitutive androstane receptor (Car; official symbol Nr1i3), were downregulated. Quercetin decreased high-fat diet induced body weight gain, hepatic lipid accumulation and serum lipid levels. This was accompanied by regulation of cytochrome P450 2b genes in liver, which are possibly under transcriptional control of CAR. The quercetin effects are likely dependent on the fat content of the diet.

  12. Application of Bioactive Quercetin in Oncotherapy: From Nutrition to Nanomedicine.

    PubMed

    Nam, Ju-Suk; Sharma, Ashish Ranjan; Nguyen, Lich Thi; Chakraborty, Chiranjib; Sharma, Garima; Lee, Sang-Soo

    2016-01-01

    Phytochemicals as dietary constituents are being explored for their cancer preventive properties. Quercetin is a major constituent of various dietary products and recently its anti-cancer potential has been extensively explored, revealing its anti-proliferative effect on different cancer cell lines, both in vitro and in vivo. Quercetin is known to have modulatory effects on cell apoptosis, migration and growth via various signaling pathways. Though, quercetin possesses great medicinal value, its applications as a therapeutic drug are limited. Problems like low oral bioavailability and poor aqueous solubility make quercetin an unreliable candidate for therapeutic purposes. Additionally, the rapid gastrointestinal digestion of quercetin is also a major barrier for its clinical translation. Hence, to overcome these disadvantages quercetin-based nanoformulations are being considered in recent times. Nanoformulations of quercetin have shown promising results in its uptake by the epithelial system as well as enhanced delivery to the target site. Herein we have tried to summarize various methods utilized for nanofabrication of quercetin formulations and for stable and sustained delivery of quercetin. We have also highlighted the various desirable measures for its use as a promising onco-therapeutic agent. PMID:26797598

  13. Quercetin protects against aluminium induced oxidative stress and promotes mitochondrial biogenesis via activation of the PGC-1α signaling pathway.

    PubMed

    Sharma, Deep Raj; Sunkaria, Aditya; Wani, Willayat Yousuf; Sharma, Reeta Kumari; Verma, Deepika; Priyanka, Kumari; Bal, Amanjit; Gill, Kiran Dip

    2015-12-01

    The present investigation was carried out to elucidate a possible molecular mechanism related to the protective effect of quercetin administration against aluminium-induced oxidative stress on various mitochondrial respiratory complex subunits with special emphasis on the role of PGC-1α and its downstream targets, i.e. NRF-1, NRF-2 and Tfam in mitochondrial biogenesis. Aluminium lactate (10mg/kg b.wt./day) was administered intragastrically to rats, which were pre-treated with quercetin 6h before aluminium (10mg/kg b.wt./day, intragastrically) for 12 weeks. We found a decrease in ROS levels, mitochondrial DNA oxidation and citrate synthase activity in the hippocampus (HC) and corpus striatum (CS) regions of rat brain treated with quercetin. Besides this an increase in the mRNA levels of the mitochondrial encoded subunits - ND1, ND2, ND3, Cyt b, COX1, COX3 and ATPase6 along with increased expression of nuclear encoded subunits COX4, COX5A and COX5B of electron transport chain (ETC). In quercetin treated group an increase in the mitochondrial DNA copy number and mitochondrial content in both the regions of rat brain was observed. The PGC-1α was up regulated in quercetin treated rats along with NRF-1, NRF-2 and Tfam, which act downstream from PGC-1α. Electron microscopy results revealed a significant decrease in the mitochondrial cross-section area, mitochondrial perimeter length and increase in mitochondrial number in case of quercetin treated rats as compared to aluminium treated ones. Therefore it seems quercetin increases mitochondrial biogenesis and makes it an almost ideal flavanoid to control or limit the damage that has been associated with the defective mitochondrial function seen in many neurodegenerative diseases.

  14. Differential protein expression of peroxiredoxin I and II by benzo(a)pyrene and quercetin treatment in 22Rv1 and PrEC prostate cell lines

    SciTech Connect

    Chaudhary, Amit; Pechan, Tibor; Willett, Kristine L. . E-mail: kwillett@olemiss.edu

    2007-04-15

    Mechanisms of benzo(a)pyrene (BaP)-mediated toxicity and chemopreventative potential of quercetin in prostate cancer are poorly understood. Two-dimensional gel electrophoresis was used to map the differences in protein expression in BaP (1 {mu}M)- and quercetin (5 {mu}M)-treated 22Rv1 human prostate cancer cells. As compared to DMSO, 26 proteins in BaP and 41 proteins in quercetin were found to be differentially expressed ({+-} 2-fold). Western blots confirmed that BaP increased peroxiredoxin (Prx) Prx I and decreased Prx II in 22Rv1 cells. Similar results were found in PrEC normal prostate epithelial cells. Quercetin (up to 10 {mu}M) upregulated Prx II without altering Prx I levels in 22Rv1 cells whereas in PrEC cells, it did not alter the constitutive protein expression of Prx I or II. The lack of quercetin-mediated changes in Prx expression suggests that quercetin does not interfere with H{sub 2}O{sub 2} levels, and thus may have no deleterious effect in normal prostate cells. Quercetin inhibited both BaP-mediated effects on Prx I and II in 22Rv1 cells. In PrEC cells, quercetin inhibited BaP-mediated upregulation of Prx I and had tendency to neutralize BaP-mediated downregulation of Prx II. Quercetin also inhibited BaP-induced concentrations of reactive oxygen species in both 22Rv1 and PrEC cells. These results suggest that Prx I and II may be involved in BaP-mediated toxicity and the potential chemopreventative mechanisms of quercetin.

  15. Modulation of the Expression of the GABAA Receptor β1 and β3 Subunits by Pretreatment with Quercetin in the KA Model of Epilepsy in Mice

    PubMed Central

    Moghbelinejad, Sahar; Rashvand, Zahra; Khodabandehloo, Fatemeh; Mohammadi, Ghazaleh

    2016-01-01

    Objectives: Quercetin is a flavonoid and an important dietary constituent of fruits and vegetables. In recent years, several pharmacological activities of quercetin, such as its neuroprotective activity and, more specifically, its anti-convulsant effects in animal models of epilepsy, have been reported. This study evaluated the role of quercetin pretreatment on gene expression of γ-amino butyric acid type A (GABAA) receptor beta subunits in kainic acid (KA)-induced seizures in mice. Methods: The animals were divided into four groups: one saline group, one group in which seizures were induced by using KA (10 mg/kg) without quercetin pretreatment and two groups pretreated with quercetin (50 and 100 mg/kg) prior to seizures being induced by using KA. Next, the messenger ribonucleic acid (mRNA) levels of the GABAA receptor β subunits in the hippocampus of each animal were assessed at 2 hours and 7 days after KA administration. Quantitative real-time polymerase chain reaction (RT-PCR) assay was used to detect mRNA content in hippocampal tissues. Results: Pretreatments with quercetin at doses of 50 and 100 mg/kg prevented significant increases in the mRNA levels of the β1 and the β3 subunits of the GABAA receptor at 2 hours after KA injection. Pretreatment with quercetin (100 mg/kg) significantly inhibited β1 and β3 gene expression in the hippocampus at 7 days after KA injection. But, this inhibitory effect of quercetin at 50 mg/kg on the mRNA levels of the β3 subunit of the GABAA receptor was not observed at 7 days after KA administration. Conclusion: These results suggest that quercetin (100 mg/kg) modulates the expression of the GABAA receptor β1 and β3 subunits in the KA model of epilepsy, most likely to prevent compensatory responses. This may be related to the narrow therapeutic dose range for the anticonvulsant activities of quercetin. PMID:27386150

  16. Quercetin ameliorates paclitaxel-induced neuropathic pain by stabilizing mast cells, and subsequently blocking PKCε-dependent activation of TRPV1

    PubMed Central

    Gao, Wei; Zan, Yan; Wang, Zai-jie Jim; Hu, Xiao-yu; Huang, Fang

    2016-01-01

    Aim: Severe painful sensory neuropathy often occurs during paclitaxel chemotherapy. Since paclitaxel can activate mast cell and basophils, whereas quercetin, a polyphenolic flavonoid contained in various plants, which can specifically inhibit histamine release as a mast cell stabilizer. In this study we explore whether quercetin could ameliorate paclitaxel-induced neuropathic pain and elucidated the underlying mechanisms. Methods: Quercetin inhibition on histamine release was validated in vitro by detecting histamine release from rat basophilic leukemia (RBL-2H3) cells stimulated with paclitaxel (10 μmol/L). In the in vivo experiments, rats and mice received quercetin (20, 40 mg·kg-1·d-1) for 40 and 12 d, respectively. Meanwhile, the animals were injected with paclitaxel (2 mg/kg, ip) four times on d 1, 3, 5 and 7. Heat hyperalgesia and mechanical allodynia were evaluated at the different time points. The animals were euthanized and spinal cords and dorsal root ganglions were harvested for analyzing PKCε and TRPV1 expression levels. The plasma histamine levels were assessed in rats on d 31. Results: Pretreatment with quercetin (3, 10, 30 μmol/L) dose-dependently inhibited excessive histamine release from paclitaxel-stimulated RBL-2H3 cells in vitro, and quercetin administration significantly suppressed the high plasma histamine levels in paclitaxel-treated rats. Quercetin administration dose-dependently raised the thresholds for heat hyperalgesia and mechanical allodynia in paclitaxel-treated rats and mice. Furthermore, quercetin administration dose-dependently suppressed the increased expression levels of PKCε and TRPV1 in the spinal cords and DRGs of paclitaxel-treated rats and mice. Moreover, quercetin administration may inhibited the translocation of PKCε from the cytoplasm to the membrane in the spinal cord and DRG of paclitaxel-treated rats. Conclusion: Our results reveal the underlying mechanisms of paclitaxel-induced peripheral neuropathy and

  17. [Time resolved UV-Vis absorption spectra of quercetin reacting with various concentrations of sodium hydroxide].

    PubMed

    Yang, Li-Jun; Li, Ping; Gao, Yan-Jun; Li, Hui-Feng; Wu, Da-Cheng; Li, Rui-Xia

    2009-06-01

    A real time investigation of chemical reaction process of quercetin with various concentrations of sodium hydroxide was performed by using an intensified spectroscopic detector ICCD. The time resolved UV-Vis absorption spectra of 5 x 10(-5) mol x L(-1) quercetin respectively reacting with sodium hydroxide at concentrations of 2, 0.2, 0.1, 0.04 and 0.02 mol x L(-1) were acquired. A total of 200 spectra with the same exposure time of 0.1 ms for each spectrum but different time interval between two consecutive spectra were recorded for each reaction. The first 50 spectra have the time interval of 20 ms, the next 50 have 1 s, and the last 100 have 2 s. Results indicate that quercetin reacted with sodium hydroxide easily and there was an intermediate product formed during the reaction, with different concentrations of reactants, the changes of absorption bands were the same, but the moments at which the changes happened were different and the total reaction time was various from 1 s to 100 s. Spectra recorded showed the disappearing process of the typical bands centered at 254 and 374 nm of pure quercetin, the growing and disappearing processes of a new band centered at 427 nm of the intermediate product, and the growing process of the new band centered at 314 nm of the final product obviously. No other transient spectroscopic data are currently available on the reaction of quercrtin with sodium hydroxide, the results obtained in the present work provide useful experimental data for the study of the microscopic process of the reaction.

  18. Natural flavonoids silymarin and quercetin improve the brain distribution of co-administered P-gp substrate drugs.

    PubMed

    Ravikumar Reddy, D; Khurana, Amit; Bale, Swarna; Ravirala, Ramu; Samba Siva Reddy, V; Mohankumar, M; Godugu, Chandraiah

    2016-01-01

    P-glycoprotein (P-gp), a well known efflux transporter in the blood brain barrier inhibits the uptake of substrate drugs into brain. The main aim of this study is to evaluate the effect of natural product based P-gp inhibitors on brain penetration of various CNS drugs which are P-gp substrates. In this study, we have evaluated the inhibitory effects of natural bioflavonoids (quercetin and silymarin) on P-gp by using digoxin and quinidine as model P-gp model substrate drugs. In vitro inhibitory effects were evaluated in Caco-2 cell lines using digoxin as a model drug and in vivo P-gp inhibiting effect was evaluated in mice model using quinidine as model drug. The accumulation and bidirectional transport of digoxin in Caco-2 cells was determined in presence and absence of quercetin and silymarin. Elacridar was used as standard P-gp inhibitor and used to compare the inhibitory effects of test compounds. The apical to basolateral transport of digoxin was increased where as basolateral to apical transport of digoxin was decreased in concentration dependent manner in the presence of elacridar, quercetin and silymarin. After intravenous administration of P-gp inhibitors, brain levels of quinidine were estimated using LC-MS method. Increased brain uptake was observed with quercetin (2.5-fold) and silymarin (3.5-fold). Though the brain penetration potential of P-gp substrates was lower than that observed in elacridar, both quercetin and silymarin improved plasma quinidine levels. Caco-2 permeability studies and brain uptake indicate that both quercetin and silymarin can inhibit P-gp mediated efflux of drug into brain. Our results suggest that both silymarin and quercetin could potentially increase the brain distribution of co-administered drugs that are P-gp substrates.

  19. Natural flavonoids silymarin and quercetin improve the brain distribution of co-administered P-gp substrate drugs.

    PubMed

    Ravikumar Reddy, D; Khurana, Amit; Bale, Swarna; Ravirala, Ramu; Samba Siva Reddy, V; Mohankumar, M; Godugu, Chandraiah

    2016-01-01

    P-glycoprotein (P-gp), a well known efflux transporter in the blood brain barrier inhibits the uptake of substrate drugs into brain. The main aim of this study is to evaluate the effect of natural product based P-gp inhibitors on brain penetration of various CNS drugs which are P-gp substrates. In this study, we have evaluated the inhibitory effects of natural bioflavonoids (quercetin and silymarin) on P-gp by using digoxin and quinidine as model P-gp model substrate drugs. In vitro inhibitory effects were evaluated in Caco-2 cell lines using digoxin as a model drug and in vivo P-gp inhibiting effect was evaluated in mice model using quinidine as model drug. The accumulation and bidirectional transport of digoxin in Caco-2 cells was determined in presence and absence of quercetin and silymarin. Elacridar was used as standard P-gp inhibitor and used to compare the inhibitory effects of test compounds. The apical to basolateral transport of digoxin was increased where as basolateral to apical transport of digoxin was decreased in concentration dependent manner in the presence of elacridar, quercetin and silymarin. After intravenous administration of P-gp inhibitors, brain levels of quinidine were estimated using LC-MS method. Increased brain uptake was observed with quercetin (2.5-fold) and silymarin (3.5-fold). Though the brain penetration potential of P-gp substrates was lower than that observed in elacridar, both quercetin and silymarin improved plasma quinidine levels. Caco-2 permeability studies and brain uptake indicate that both quercetin and silymarin can inhibit P-gp mediated efflux of drug into brain. Our results suggest that both silymarin and quercetin could potentially increase the brain distribution of co-administered drugs that are P-gp substrates. PMID:27652191

  20. Bioavailability of quercetin: problems and promises.

    PubMed

    Cai, X; Fang, Z; Dou, J; Yu, A; Zhai, G

    2013-01-01

    Quercetin (QC) is a typical plant flavonoid, possesses diverse pharmacologic effects including antiinflammatory, antioxidant, anti-cancer, anti-anaphylaxis effects and against aging. However, the application of QC in pharmaceutical field is limited due to its poor solubility, low bioavailability, poor permeability and instability. To improve the bioavailability of QC, numerous approaches have been undertaken, involving the use of promising drug delivery systems such as inclusion complexes, liposomes, nanoparticles or micelles, which appear to provide higher solubility and bioavailability. Enhanced bioavailability of QC in the near future is likely to bring this product to the forefront of therapeutic agents for treatment of human disease.

  1. Arctigenin in combination with quercetin synergistically enhances the anti-proliferative effect in prostate cancer cells

    PubMed Central

    Wang, Piwen; Phan, Tien; Gordon, David; Chung, Seyung; Henning, Susanne M.; Vadgama, Jaydutt V.

    2014-01-01

    Scope We investigated whether a combination of two promising chemopreventive agents arctigenin and quercetin increases the anti-carcinogenic potency at lower concentrations than necessary when used individually in prostate cancer. Methods and results Androgen-dependent LAPC-4 and LNCaP prostate cancer cells were treated with low doses of arctigenin and quercetin alone or in combination for 48h. The anti-proliferative activity of arctigenin was 10-20 fold stronger than quercetin in both cell lines. Their combination synergistically enhanced the anti-proliferative effect, with a stronger effect in androgen receptor (AR) wild-type LAPC-4 cells than in AR mutated LNCaP cells. Arctigenin demonstrated a strong ability to inhibit AR protein expression in LAPC-4 cells. The combination treatment significantly inhibited both AR and PI3K/Akt pathways compared to control. A protein array analysis revealed that the mixture targets multiple pathways particularly in LAPC-4 cells including Stat3 pathway. The mixture significantly inhibited the expression of several oncogenic microRNAs including miR-21, miR-19b, and miR-148a compared to control. The mixture also enhanced the inhibition of cell migration in both cell lines compared to individual compounds tested. Conclusion The combination of arctigenin and quercetin, that target similar pathways, at low physiological doses, provides a novel regimen with enhanced chemoprevention in prostate cancer. PMID:25380086

  2. Kaempferol and quercetin glycosides from Rubus idaeus L. leaves.

    PubMed

    Gudej, Jan

    2003-01-01

    Quercetin 3-0-beta-D-glucoside (I), quercetin and kaempferol 3-0-beta-D-galactosides (II, III), kaempferol 3-0-beta-L-arabinopyranoside (IV), kaempferol 3-0-beta-D-(6''-E-p-coumaroyl)-glucoside (tiliroside) (V) and methyl gallate (VI) were isolated from Rubus idaeus L. subspecies culture of Norna leaves and fully characterized.

  3. Quercetin Reduces Ehrlich Tumor-Induced Cancer Pain in Mice

    PubMed Central

    Calixto-Campos, Cassia; Corrêa, Mab P.; Carvalho, Thacyana T.; Zarpelon, Ana C.; Hohmann, Miriam S. N.; Rossaneis, Ana C.; Coelho-Silva, Leticia; Pavanelli, Wander R.; Pinge-Filho, Phileno; Crespigio, Jefferson; Bernardy, Catia C. F.; Casagrande, Rubia; Verri, Waldiceu A.

    2015-01-01

    Cancer pain directly affects the patient's quality of life. We have previously demonstrated that the subcutaneous administration of the mammary adenocarcinoma known as Ehrlich tumor induces pain in mice. Several studies have shown that the flavonoid quercetin presents important biological effects, including anti-inflammatory, antioxidant, analgesic, and antitumor activity. Therefore, the analgesic effect and mechanisms of quercetin were evaluated in Ehrlich tumor-induced cancer pain in mice. Intraperitoneal (i.p.) treatments with quercetin reduced Ehrlich tumor-induced mechanical and thermal hyperalgesia, but not paw thickness or histological alterations, indicating an analgesic effect without affecting tumor growth. Regarding the analgesic mechanisms of quercetin, it inhibited the production of hyperalgesic cytokines IL-1β and TNFα and decreased neutrophil recruitment (myeloperoxidase activity) and oxidative stress. Naloxone (opioid receptor antagonist) inhibited quercetin analgesia without interfering with neutrophil recruitment, cytokine production, and oxidative stress. Importantly, cotreatment with morphine and quercetin at doses that were ineffective as single treatment reduced the nociceptive responses. Concluding, quercetin reduces the Ehrlich tumor-induced cancer pain by reducing the production of hyperalgesic cytokines, neutrophil recruitment, and oxidative stress as well as by activating an opioid-dependent analgesic pathway and potentiation of morphine analgesia. Thus, quercetin treatment seems a suitable therapeutic approach for cancer pain that merits further investigation. PMID:26351625

  4. TOPAZ: The transient one-dimensional pipe flow analyzer: An update on code improvements and increased capabilities

    SciTech Connect

    Winters, W.S.

    1987-09-01

    TOPAZ is a ''user-friendly'' computer code for modeling the one-dimensional, transient physics of multi-species gas transfer in arbitrary arrangements of pipes, valves, vessels, and flow branches. This report, the fourth in a series of reports documenting TOPAZ, discusses coding improvements and the addition of new capabilities. These improvements make the current version of TOPAZ considerably more versatile than the original version which was distributed last year. For example, the new version does not restrict the user to modeling only hydrogen and helium isotope flows. Users now have the capability of modeling arbitrary gas mixture flows. In addition users may define time-dependent functions for mass generation, energy deposition, flow area, and maximum integration time step. Parallel flow paths and flows through channels having noncircular cross-sections may now be simulated. Improvements in TOPAZ mesh generation have been made which permit users to add additional ''plumbing'' to existing models without renumbering the mesh. 7 refs., 3 figs., 8 tabs.

  5. In Vitro Antiophidian Mechanisms of Hypericum brasiliense Choisy Standardized Extract: Quercetin-Dependent Neuroprotection

    PubMed Central

    Lucho, Ana Paula de Bairros; Vinadé, Lúcia; Seibert França, Hildegardo; Marangoni, Sérgio; Rodrigues-Simioni, Léa

    2013-01-01

    The neuroprotection induced by Hypericum brasiliense Choisy extract (HBE) and its main active polyphenol compound quercetin, against Crotalus durissus terrificus (Cdt) venom and crotoxin and crotamine, was enquired at both central and peripheral mammal nervous system. Cdt venom (10 μg/mL) or crotoxin (1 μg/mL) incubated at mouse phrenic nerve-diaphragm preparation (PND) induced an irreversible and complete neuromuscular blockade, respectively. Crotamine (1 μg/mL) only induced an increase of muscle strength at PND preparations. At mouse brain slices, Cdt venom (1, 5, and 10 μg/mL) decreased cell viability. HBE (100 μg/mL) inhibited significantly the facilitatory action of crotamine (1 μg/mL) and was partially active against the neuromuscular blockade of crotoxin (1 μg/mL) (data not shown). Quercetin (10 μg/mL) mimicked the neuromuscular protection of HBE (100 μg/mL), by inhibiting almost completely the neurotoxic effect induced by crotoxin (1 μg/mL) and crotamine (1 μg/mL). HBE (100 μg/mL) and quercetin (10 μg/mL) also increased cell viability in mice brain slices. Quercetin (10 μg/mL) was more effective than HBE (100 μg/mL) in counteracting the cell lysis induced by Cdt venom (1 and 10 μg/mL, resp.). These results and a further phytochemical and toxicological investigations could open new perspectives towards therapeutic use of Hypericum brasiliense standardized extract and quercetin, especially to counteract the neurotoxic effect induced by snake neurotoxic venoms. PMID:24490174

  6. Quercetinase pirin makes poliovirus replication resistant to flavonoid quercetin.

    PubMed

    Neznanov, Nickolay; Kondratova, Anna; Chumakov, Konstantin M; Neznanova, Lubov; Kondratov, Roman; Banerjee, Amiya K; Gudkov, Andrei V

    2008-04-01

    Flavonoid quercetin and its derivative, methylquercetin, inhibit the replication of poliovirus in several cell lines. Here, we show that replication of poliovirus is inhibited by quercetin and that the extent of this inhibition depends on the intracellular content of pirin, a quercetinase. HeLa cells contain higher content of pirin protein than normal kidney human epithelial (NKE) or 293 cells do. Poliovirus replication in HeLa cells is significantly more resistant to quercetin than its replication in NKE and 293 cells. Overexpression of pirin reduced antiviral inhibitory effect of quercetin, while siRNA-induced suppression of pirin level made poliovirus replication more sensitive to the flavonoid. The results suggest that quercetinase activity of pirin determines the resistance of poliovirus infection to quercetin.

  7. Dopaminergic agonists that result in ocular growth inhibition also elicit transient increases in choroidal thickness in chicks.

    PubMed

    Nickla, Debora L; Totonelly, Kristen; Dhillon, Balprit

    2010-11-01

    The dopaminergic system has been implicated in ocular growth regulation in chicks and monkeys. In both, dopamine D2 agonists inhibit the development of myopia in response to form deprivation, and in chicks, to negative lenses as well. Because there is mounting evidence that the choroidal response to defocus plays a role in ocular growth regulation, we asked whether the effective agonists also elicit transient thickening of the choroid concomitant with the growth inhibition. Negative lenses mounted on velcro rings were worn on one eye starting at age 8-12 days. Intravitreal injections (20 μl; dose = 10 nmole) of the agonist (dissolved in saline) or saline, were given through the superior temporal sclera using a 30G needle. Eyes were injected daily at noon, for 4 days, and the lenses immediately replaced. Agonists used were apomorphine (non-specific; n = 17), quinpirole (D2; n = 10), SKF-38393 (D1; n = 9), and saline controls (n = 22). For the antagonists, the same protocol was used, but on each day, the lenses were removed for 2 h. Immediately prior to lens-removal, the antagonist was injected (20 μl; dose = 5 nmole). Antagonists used were methylergonovine (non-specific; n = 12), spiperone (D2; n = 20), SCH-23390 (D1; n = 6) and saline controls (n = 27). Comparisons to saline (continuous lens wear) controls were from the agonist experiment. Axial dimensions were measured using high frequency A-scan ultrasonography at the start of lens wear, and on day 4 prior to the injections, and then again 3 h later. Refractive errors were measured using a Hartinger's refractometer at the end of the experiment. Apomorphine and quinpirole inhibited the refractive response to the hyperopic defocus induced by the negative lenses (drug vs saline controls: -1.3 and 1.2 D vs -5.6 D; p < 0.005 for both). This effect was axial: both drugs prevented the excessive ocular elongation (change in axial length: 233 and 205 μm vs 417 μm; p < 0.01 for both

  8. Enhancement of the in vitro penetration of quercetin through pig skin by combined microneedles and lipid microparticles.

    PubMed

    Paleco, Roberto; Vučen, Sonja R; Crean, Abina M; Moore, Anne; Scalia, Santo

    2014-09-10

    Silicon microneedle patches were investigated, alone or in combination with lipid microparticles (LMs), as a system to improve the in vitro skin penetration of the antioxidant flavonoid, quercetin. LMs loaded with quercetin were prepared by melt emulsification and sonication. The flavonoid content of LMs was 11.7±0.3% and their mean diameter and polydispersity index were 8.1 μm and 0.66, respectively. Emulsions containing quercetin, free or microencapsulated, were applied to untreated- or microneedle-treated pig skin mounted in Franz diffusion cells. The amount of flavonoid penetrated into the stratum corneum and viable epidermis were measured by HPLC, after validated tape-stripping and bead mill homogenization procedures, respectively. Compared to intact skin, a marked increase in quercetin levels permeated into the stratum corneum (from 1.19 ± 0.12 μg/cm(2) to 2.23 ± 0.54 μg/cm(2)) and viable epidermis (from 0.10 ± 0.01 μg/cm(2) to 0.56 ± 0.27 μg/cm(2)) was achieved when skin was treated with the flavonoid-loaded LMs in combination with microneedle arrays. Conversely, perforation of the cutaneous surface by microneedles did not produce any significant improvement in the skin penetration of non-encapsulated quercetin. The enhanced (5.5-fold) intra-epidermal delivery of quercetin attained by the LM/microneedle strategy described here, is particularly relevant since the main quercetin site of action is in the epidermis.

  9. Absorption and disposition of naringenin and quercetin after simultaneous administration via intestinal perfusion in mice.

    PubMed

    Orrego-Lagarón, Naiara; Martínez-Huélamo, Miriam; Quifer-Rada, Paola; Lamuela-Raventos, Rosa M; Escribano-Ferrer, Elvira

    2016-09-14

    As common constituents of tomatoes and other fruits and/or vegetables, naringenin and quercetin are usually ingested together, so for a clearer understanding of their bioavailability, metabolic fates and health benefits, it is more insightful to study them together. The purpose of the present work was to study how co-administration of naringenin and quercetin at realistic doses (3.5 μg ml(-1) and 2.36 μg ml(-1), respectively) influences their absorption and intestinal first-pass metabolism. A single-pass intestinal perfusion model in mice (n = 4-6) was used. Perfusate (every 10 minutes), blood (at 60 min) and bile samples were analysed by an UPLC-ESI-MS/MS method to evaluate the presence of the aglycones and their metabolites. Both naringenin and quercetin showed high permeability coefficients when administered separately (7.71 ± 0.82 × 10(-4) cm s(-1)vs. 7.30 ± 1.95 × 10(-4) cm s(-1), respectively), but these values decreased by 50% with co-administration (4.09 ± 0.89 × 10(-4) cm s(-1) for naringenin and 3.18 ± 0.45 × 10(-4) cm s(-1) for quercetin). Moreover, the level of phase II metabolites in perfusion, plasma and bile samples increased when naringenin and quercetin were administered together. The higher biliary excretion of these metabolites could thus favour the entero-hepatic recycling of the aglycones and metabolites. The results of this study may have several useful applications: to know and consider the possible interactions between polyphenols and drugs that use the same mechanism of absorption and elimination; when polyphenol-rich nutritional supplements are supplied, and in our regular diets to optimize the health benefits afforded by the biological activities of such aglycones and/or metabolites.

  10. Protective effect of quercetin on cadmium-induced oxidative toxicity on germ cells in male mice.

    PubMed

    Bu, Tongliang; Mi, Yuling; Zeng, Weidong; Zhang, Caiqiao

    2011-03-01

    Cadmium is a toxic heavy metal that is widely distributed in the environment. As a critical process, oxidative toxicity mediates the morphological and functional damages in germ cells after cadmium exposure. In this study, the protective effect of quercetin on cadmium-induced oxidative toxicity was investigated in mouse testicular germ cells. After oral administration of cadmium chloride at 4 mg/kg body weight for 2 weeks, damages in spermatozoa occurred in the early stage of spermatogenesis. Cadmium treatment significantly decreased the testicular antioxidant system, including decreases in the glutathione (GSH) level, superoxide dismutase (SOD), and GSH peroxidase (GSH-Px) activities. Moreover, exposure to cadmium resulted in an increase of hydrogen peroxide production and lipid peroxidation in testes. In addition, cadmium provoked germ cell apoptosis by upregulating expression of the proapoptotic proteins Bax and caspase-3 and downregulating expression of the antiapoptotic protein Bcl-XL. However, combined administration of a common flavonoid quercetin at 75 mg/kg body weight significantly attenuated cadmium-induced germ cell apoptosis by suppressing the hydrogen peroxide production and lipid peroxidation in testicular tissue. Simultaneous supplementation of quercetin markedly restored the decrease in GSH level and SOD and GSH-Px activities elicited by cadmium treatment. Additionally, quercetin protected germ cells from cadmium-induced apoptosis by downregulating the expression of Bax and caspase-3 and upregulating Bcl-XL expression. These results indicate that quercetin, due to its antioxidative and antiapoptotic characters, may manifest effective protective action against cadmium-induced oxidative toxicity in mouse testicular germ cells. PMID:21337715

  11. The protective effects of oral low-dose quercetin on diabetic nephropathy in hypercholesterolemic mice

    PubMed Central

    Gomes, Isabele B. S.; Porto, Marcella L.; Santos, Maria C. L. F. S.; Campagnaro, Bianca P.; Gava, Agata L.; Meyrelles, Silvana S.; Pereira, Thiago M. C.; Vasquez, Elisardo C.

    2015-01-01

    Aims: Diabetic nephropathy (DN) is one of the most important causes of chronic renal disease, and the incidence of DN is increasing worldwide. Considering our previous report (Gomes et al., 2014) indicating that chronic treatment with oral low-dose quercetin (10 mg/Kg) demonstrated anti-oxidative, anti-apoptotic and renoprotective effects in the C57BL/6J model of DN, we investigated whether this flavonoid could also have beneficial effects in concurrent DN and spontaneous atherosclerosis using the apolipoprotein E-deficient mouse (apoE−/−). Methods: Streptozotocin was used to induce diabetes (100 mg/kg/day, 3 days) in male apoE−/− mice (8 week-old). After 6 weeks, the mice were randomly separated into DQ: diabetic apoE−/− mice treated with quercetin (10 mg/kg/day, 4 weeks, n = 8), DV: diabetic ApoE−/− mice treated with vehicle (n = 8) and ND: non-treated non-diabetic mice (n = 8). Results: Quercetin treatment diminished polyuria (~30%; p < 0.05), glycemia (~25%, p < 0.05), normalized the hypertriglyceridemia. Moreover, this bioflavonoid diminished creatininemia (~30%, p < 0.01) and reduced proteinuria but not to normal levels. We also observed protective effects on the renal structural changes, including normalization of the index of glomerulosclerosis and kidney weight/body weight. Conclusions: Our data revealed that quercetin treatment significantly reduced DN in hypercholesterolemic mice by inducing biochemical changes (decrease in glucose and triglycerides serum levels) and reduction of glomerulosclerosis. Thus, this study highlights the relevance of quercetin as an alternative therapeutic option for DN, including in diabetes associated with dyslipidemia. PMID:26388784

  12. Effects of low doses of quercetin and genistein on oxidation and carbonylation in hemoglobin and myoglobin.

    PubMed

    Boadi, William Y; Johnson, Damitea

    2014-09-01

    Protein-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 Fe(2+) 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. PMID:25026201

  13. Absorption and disposition of naringenin and quercetin after simultaneous administration via intestinal perfusion in mice.

    PubMed

    Orrego-Lagarón, Naiara; Martínez-Huélamo, Miriam; Quifer-Rada, Paola; Lamuela-Raventos, Rosa M; Escribano-Ferrer, Elvira

    2016-09-14

    As common constituents of tomatoes and other fruits and/or vegetables, naringenin and quercetin are usually ingested together, so for a clearer understanding of their bioavailability, metabolic fates and health benefits, it is more insightful to study them together. The purpose of the present work was to study how co-administration of naringenin and quercetin at realistic doses (3.5 μg ml(-1) and 2.36 μg ml(-1), respectively) influences their absorption and intestinal first-pass metabolism. A single-pass intestinal perfusion model in mice (n = 4-6) was used. Perfusate (every 10 minutes), blood (at 60 min) and bile samples were analysed by an UPLC-ESI-MS/MS method to evaluate the presence of the aglycones and their metabolites. Both naringenin and quercetin showed high permeability coefficients when administered separately (7.71 ± 0.82 × 10(-4) cm s(-1)vs. 7.30 ± 1.95 × 10(-4) cm s(-1), respectively), but these values decreased by 50% with co-administration (4.09 ± 0.89 × 10(-4) cm s(-1) for naringenin and 3.18 ± 0.45 × 10(-4) cm s(-1) for quercetin). Moreover, the level of phase II metabolites in perfusion, plasma and bile samples increased when naringenin and quercetin were administered together. The higher biliary excretion of these metabolites could thus favour the entero-hepatic recycling of the aglycones and metabolites. The results of this study may have several useful applications: to know and consider the possible interactions between polyphenols and drugs that use the same mechanism of absorption and elimination; when polyphenol-rich nutritional supplements are supplied, and in our regular diets to optimize the health benefits afforded by the biological activities of such aglycones and/or metabolites. PMID:27515345

  14. Antidiabetic and antioxidative effects of Annona squamosa leaves are possibly mediated through quercetin-3-O-glucoside.

    PubMed

    Panda, Sunanda; Kar, Anand

    2007-01-01

    Present investigation was made to reveal the involvement of a quercetin in the antidiabetic and antiperoxidative effects of Annona squamosa leaf extract. Quercetin-3-O-glucoside (characterized by UV, IR, MS and NMR analyses) was isolated from Annona squamosa leaves and examined for its potential to regulate alloxan-induced hyperglycemia and lipid peroxidation (LPO) in rats. While in alloxan treated animals, an increase in the concentration of serum glucose with a parallel decrease in insulin level was observed, administration of 15 mg/kg/day of isolated quercetin-3-O-glucoside for 10 consecutive days to the hyperglycemic animals reversed these effects and simultaneously inhibited the activity of hepatic glucose-6-phosphatase. It further decreased the hepatic and renal LPO with a concomitant increase in the activities of antioxidative enzymes, such as catalase (CAT) and superoxide dismutase (SOD) and in glutathione (GSH) content, indicating its safe and antiperoxidative effects. These findings suggest the potential of quercetin-3-O-glucoside in the amelioration of diabetes mellitus and tissue lipid peroxidation. It also appears that the antidiabetic effects of A. squamosa leaf extract is possibly mediated through the insulin stimulating and/or free radical scavenging properties of its active constituent, quercetin-3-O-glucoside. PMID:18997283

  15. Protective effects of kolaviron and quercetin on cadmium-induced testicular damage and endocrine pathology in rats.

    PubMed

    Farombi, E O; Adedara, I A; Akinrinde, S A; Ojo, O O; Eboh, A S

    2012-08-01

    This study evaluated the effects of kolaviron, a biflavonoid from Garcinia kola seed, and quercetin on cadmium-induced reproductive toxicity in rats. Adult male rats were administered with either cadmium (15 mg kg(-1)) alone or in combination with kolaviron (200 mg kg(-1)) or quercetin (10 mg kg(-1)) daily for 5 days. Cadmium-treated rats showed (P < 0.05) decrease in the body weight gain, testis and epididymis weights. However, upon co-administration of kolaviron or quercetin, these changes were significantly reversed in cadmium-treated rats. Also, administration of kolaviron or quercetin significantly prevented cadmium-mediated decrease in sperm motility and epididymal sperm concentration and reversed the increased level of sperm abnormality to near control. In testes and sperm, cadmium treatment resulted in significant decrease in the activities of superoxide dismutase, catalase and glutathione peroxidase, whereas it increased glutathione S-transferase activity as well as hydrogen peroxide and malondialdehyde levels. While plasma levels of triiodothyronine and tetraiodothyronine remained unaffected, the levels of testosterone, luteinising hormone and follicle stimulating hormone were decreased in cadmium-treated rats. Cadmium treatment caused mild congestion of interstitial vessels and oedema in the testes. Taken together, kolaviron and quercetin inhibited the adverse effects of cadmium on the antioxidant enzymes, markers of oxidative stress, endocrine and testicular structure in rats. PMID:22356231

  16. Acetonic and Methanolic Extracts of Heterotheca inuloides, and Quercetin, Decrease CCl4-Oxidative Stress in Several Rat Tissues

    PubMed Central

    Coballase-Urrutia, Elvia; Pedraza-Chaverri, José; Cárdenas-Rodríguez, Noemí; Huerta-Gertrudis, Bernardino; García-Cruz, Mercedes Edna; Montesinos-Correa, Hortencia; Sánchez-González, Dolores Javier; Camacho-Carranza, Rafael; Espinosa-Aguirre, Jesús Javier

    2013-01-01

    The present study was designed to test the hypothesis that the acetonic and methanolic extracts of H. inuloides prevent carbon tetrachloride-(CCl4) induced oxidative stress in vital tissues. Pretreatment with both H. inuloides extracts or quercetin attenuated the increase in serum activity of alkaline phosphatase (ALP), total bilirubin (BB), creatinine (CRE), and creatine kinase (CK), and impeded the decrease of γ-globulin (γ-GLOB) and albumin (ALB) observed in CCl4-induced tissue injury. The protective effect was confirmed by histological analysis with hematoxylin-eosin and periodic acid/Schiff's reagent. Level of lipid peroxidation was higher in the organs of rats exposed to CCl4 than in those of the animals treated with Heterohteca extracts or quercetin, and these showed levels similar to the untreated group. Pretreatment of animals with either of the extracts or quercetin also prevented the increase of 4-hydroxynonenal and 3-nitrotyrosine. Pretreatment with the plant extracts or quercetin attenuated CCl4 toxic effects on the activity of several antioxidant enzymes. The present results strongly suggest that the chemopreventive effect of the extracts used and quercetin, against CCl4 toxicity, is associated with their antioxidant properties and corroborated previous results obtained in liver tissue. PMID:23365610

  17. Transiently Increasing cAMP Levels Selectively in Hippocampal Excitatory Neurons during Sleep Deprivation Prevents Memory Deficits Caused by Sleep Loss

    PubMed Central

    Bruinenberg, Vibeke M.; Tudor, Jennifer C.; Ferri, Sarah L.; Baumann, Arnd; Meerlo, Peter

    2014-01-01

    The hippocampus is particularly sensitive to sleep loss. Although previous work has indicated that sleep deprivation impairs hippocampal cAMP signaling, it remains to be determined whether the cognitive deficits associated with sleep deprivation are caused by attenuated cAMP signaling in the hippocampus. Further, it is unclear which cell types are responsible for the memory impairments associated with sleep deprivation. Transgenic approaches lack the spatial resolution to manipulate specific signaling pathways selectively in the hippocampus, while pharmacological strategies are limited in terms of cell-type specificity. Therefore, we used a pharmacogenetic approach based on a virus-mediated expression of a Gαs-coupled Drosophila octopamine receptor selectively in mouse hippocampal excitatory neurons in vivo. With this approach, a systemic injection with the receptor ligand octopamine leads to increased cAMP levels in this specific set of hippocampal neurons. We assessed whether transiently increasing cAMP levels during sleep deprivation prevents memory consolidation deficits associated with sleep loss in an object–location task. Five hours of total sleep deprivation directly following training impaired the formation of object–location memories. Transiently increasing cAMP levels in hippocampal neurons during the course of sleep deprivation prevented these memory consolidation deficits. These findings demonstrate that attenuated cAMP signaling in hippocampal excitatory neurons is a critical component underlying the memory deficits in hippocampus-dependent learning tasks associated with sleep deprivation. PMID:25411499

  18. Comparison of the bioavailability of quercetin and catechin in rats.

    PubMed

    Manach, C; Texier, O; Morand, C; Crespy, V; Régérat, F; Demigné, C; Rémésy, C

    1999-12-01

    Quercetin and catechin are present in noticeable amounts in human diet and these polyphenolic compounds are supposed to exert beneficial effects on human health. However, their metabolic fates in the organism have never been compared. In the present study, rats were fed a 0.25% quercetin or a 0.25% catechin diet. Quercetin and catechin metabolites were analyzed in plasma and liver samples by high-performance liquid chromatography coupled to an ultraviolet or a multielectrode coulometric detection. All plasma metabolites were present as conjugated forms, but catechin metabolites were mainly constituted by glucuronidated derivatives, whereas quercetin metabolites were sulfo- and glucurono-sulfo conjugates. Quercetin was more intensively methylated than catechin in plasma. The plasma quercetin metabolites are well maintained during the postabsorptive period (approximately 50 microM), whereas the concentration of catechin metabolites dropped dramatically between 12- and 24-h after an experimental meal (from 38.0 to 4.5 microM). In the liver, the concentrations of quercetin and catechin derivatives were lower than in plasma, and no accumulation was observed when the rats were adapted for 14 d to the supplemented diets. The hepatic metabolites were intensively methylated (90-95%), but in contrast to plasma, some free aglycones could be detected. Thus, it clearly appears that studies dealing with the biological impact of these polyphenols should take into account the feature of their bioavailability, particularly the fact that their circulating metabolites are conjugated derivatives. PMID:10641719

  19. Comparison of the bioavailability of quercetin and catechin in rats.

    PubMed

    Manach, C; Texier, O; Morand, C; Crespy, V; Régérat, F; Demigné, C; Rémésy, C

    1999-12-01

    Quercetin and catechin are present in noticeable amounts in human diet and these polyphenolic compounds are supposed to exert beneficial effects on human health. However, their metabolic fates in the organism have never been compared. In the present study, rats were fed a 0.25% quercetin or a 0.25% catechin diet. Quercetin and catechin metabolites were analyzed in plasma and liver samples by high-performance liquid chromatography coupled to an ultraviolet or a multielectrode coulometric detection. All plasma metabolites were present as conjugated forms, but catechin metabolites were mainly constituted by glucuronidated derivatives, whereas quercetin metabolites were sulfo- and glucurono-sulfo conjugates. Quercetin was more intensively methylated than catechin in plasma. The plasma quercetin metabolites are well maintained during the postabsorptive period (approximately 50 microM), whereas the concentration of catechin metabolites dropped dramatically between 12- and 24-h after an experimental meal (from 38.0 to 4.5 microM). In the liver, the concentrations of quercetin and catechin derivatives were lower than in plasma, and no accumulation was observed when the rats were adapted for 14 d to the supplemented diets. The hepatic metabolites were intensively methylated (90-95%), but in contrast to plasma, some free aglycones could be detected. Thus, it clearly appears that studies dealing with the biological impact of these polyphenols should take into account the feature of their bioavailability, particularly the fact that their circulating metabolites are conjugated derivatives.

  20. Antioxidative and antiinflammatory activities of quercetin-loaded silica nanoparticles.

    PubMed

    Lee, Ga Hyun; Lee, Sung June; Jeong, Sang Won; Kim, Hyun-Chul; Park, Ga Young; Lee, Se Geun; Choi, Jin Hyun

    2016-07-01

    Utilizing the biological activities of compounds by encapsulating natural components in stable nanoparticles is an important strategy for a variety of biomedical and healthcare applications. In this study, quercetin-loaded silica nanoparticles were synthesized using an oil-in-water microemulsion method, which is a suitable system for producing functional nanoparticles of controlled size and shape. The resulting quercetin-loaded silica nanoparticles were spherical, highly monodispersed, and stable in an aqueous system. Superoxide radical scavenging effects were found for the quercetin-loaded silica nanoparticles as well as free quercetin. The quercetin-loaded silica nanoparticles showed cell viability comparable to that of the controls. The amounts of proinflammatory cytokines produced by macrophages, such as interleukin 1 beta, interleukin 6, and tumor necrosis factor alpha, were reduced significantly for the quercetin-loaded silica nanoparticles. These results suggest that the antioxidative and antiinflammatory activities of quercetin are maintained after encapsulation in silica. Silica nanoparticles can be used for the effective and stable incorporation of biologically active natural components into composite biomaterials. PMID:27038916

  1. Enhancing oral bioavailability of quercetin using novel soluplus polymeric micelles

    NASA Astrophysics Data System (ADS)

    Dian, Linghui; Yu, Enjiang; Chen, Xiaona; Wen, Xinguo; Zhang, Zhengzan; Qin, Lingzhen; Wang, Qingqing; Li, Ge; Wu, Chuanbin

    2014-12-01

    To improve its poor aqueous solubility and stability, the potential chemotherapeutic drug quercetin was encapsulated in soluplus polymeric micelles by a modified film dispersion method. With the encapsulation efficiency over 90%, the quercetin-loaded polymeric micelles (Qu-PMs) with drug loading of 6.7% had a narrow size distribution around mean size of 79.00 ± 2.24 nm, suggesting the complete dispersibility of quercetin in water. X-ray diffraction (XRD) patterns illustrated that quercetin was in amorphous or molecular form within PMs. Fourier transform infrared spectroscopy (FTIR) indicated that quercetin formed intermolecular hydrogen bonding with carriers. An in vitro dialysis test showed the Qu-PMs possessed significant sustained-release property, and the formulation was stable for at least 6 months under accelerated conditions. The pharmacokinetic study in beagle dogs showed that absorption of quercetin after oral administration of Qu-PMs was improved significantly, with a half-life 2.19-fold longer and a relative oral bioavailability of 286% as compared to free quercetin. Therefore, these novel soluplus polymeric micelles can be applied to encapsulate various poorly water-soluble drugs towards a development of more applicable therapeutic formulations.

  2. Conjugation position of quercetin glucuronides and effect on biological activity.

    PubMed

    Day, A J; Bao, Y; Morgan, M R; Williamson, G

    2000-12-15

    Quercetin glycosides are common dietary antioxidants. In general, however, potential biological effects of the circulating plasma metabolites (e.g., glucuronide conjugates) have not been measured. We have determined the rate of glucuronidation of quercetin at each position on the polyphenol ring by human liver cell-free extracts containing UDP-glucuronosyltransferases. The apparent affinity of UDP-glucuronosyltransferase followed the order 4'- > 3'- > 7- > 3, although the apparent maximum rate of formation was for the 7-position. The 5-position did not appear to be a site for conjugation. After isolation of individual glucuronides, the inhibition of xanthine oxidase and lipoxygenase were assessed. The K(i) for the inhibition of xanthine oxidase by quercetin glucuronides followed the order 4'- > 3'- > 7- > 3-, with quercetin-4'-glucuronide a particularly potent inhibitor (K(i) = 0. 25 microM). The glucuronides, with the exception of quercetin-3-glucuronide, were also inhibitors of lipoxygenase. Quercetin glucuronides are metabolites of quercetin in humans, and these compounds can retain some biological activity depending on conjugation position at expected plasma concentrations. PMID:11118813

  3. Cell-based and in silico evidence against quercetin and structurally-related flavonols as activators of vitamin D receptor.

    PubMed

    Lau, Aik Jiang; Politi, Regina; Yang, Guixiang; Chang, Thomas K H

    2016-10-01

    It has been reported that quercetin is an activator of rat vitamin D receptor (rVDR). However, the conclusion was based on experiments performed without all the appropriate control groups, raising the possibility of a false-positive finding. Furthermore, distinct differences exist in the chemical structures of quercetin and 1α,25-dihydroxyvitamin D3, which is a prototypic agonist of VDR. Therefore, we investigated systematically whether quercetin and other flavonols are agonists of rVDR, mouse VDR (mVDR), or human VDR (hVDR). Quercetin, 3-hydroxyflavone, galangin, datiscetin, kaempferol, morin, isorhamnetin, tamarixetin, myricetin, and syringetin did not activate rVDR, mVDR, or hVDR in HEK-293 and HepG2 cells transfected with the corresponding receptor expression plasmid and either the secreted phosphoprotein 1 (Spp1) or cytochrome P450 24A1 (CYP24A1) reporter plasmid, when compared to the respective empty vector control group transfected with one or the other reporter plasmid and treated with one of the flavonols. Control analysis indicated that lithocholic acid and 1α,25-dihydroxyvitamin D3, but not rifampicin, activated rVDR, mVDR, and hVDR. As shown in transfected HEK293 and HepG2 cells, the flavonols did not influence hVDR ligand binding domain transactivation, steroid receptor coactivator-1 recruitment, or hVDR target gene expression (transient receptor potential cation channel 6 and CYP24A1) in hVDR-expressing Caco-2 or LS180 cells. The cumulative data from the cell-based experiments were corroborated by results obtained from molecular docking analysis. In conclusion, quercetin, 3-hydroxyflavone, galangin, datiscetin, kaempferol, morin, isorhamnetin, tamarixetin, myricetin, and syringetin are not agonists of rVDR, mVDR, or hVDR, as judged by cell-based and in silico evidence. PMID:27041117

  4. Cell-based and in silico evidence against quercetin and structurally-related flavonols as activators of vitamin D receptor.

    PubMed

    Lau, Aik Jiang; Politi, Regina; Yang, Guixiang; Chang, Thomas K H

    2016-10-01

    It has been reported that quercetin is an activator of rat vitamin D receptor (rVDR). However, the conclusion was based on experiments performed without all the appropriate control groups, raising the possibility of a false-positive finding. Furthermore, distinct differences exist in the chemical structures of quercetin and 1α,25-dihydroxyvitamin D3, which is a prototypic agonist of VDR. Therefore, we investigated systematically whether quercetin and other flavonols are agonists of rVDR, mouse VDR (mVDR), or human VDR (hVDR). Quercetin, 3-hydroxyflavone, galangin, datiscetin, kaempferol, morin, isorhamnetin, tamarixetin, myricetin, and syringetin did not activate rVDR, mVDR, or hVDR in HEK-293 and HepG2 cells transfected with the corresponding receptor expression plasmid and either the secreted phosphoprotein 1 (Spp1) or cytochrome P450 24A1 (CYP24A1) reporter plasmid, when compared to the respective empty vector control group transfected with one or the other reporter plasmid and treated with one of the flavonols. Control analysis indicated that lithocholic acid and 1α,25-dihydroxyvitamin D3, but not rifampicin, activated rVDR, mVDR, and hVDR. As shown in transfected HEK293 and HepG2 cells, the flavonols did not influence hVDR ligand binding domain transactivation, steroid receptor coactivator-1 recruitment, or hVDR target gene expression (transient receptor potential cation channel 6 and CYP24A1) in hVDR-expressing Caco-2 or LS180 cells. The cumulative data from the cell-based experiments were corroborated by results obtained from molecular docking analysis. In conclusion, quercetin, 3-hydroxyflavone, galangin, datiscetin, kaempferol, morin, isorhamnetin, tamarixetin, myricetin, and syringetin are not agonists of rVDR, mVDR, or hVDR, as judged by cell-based and in silico evidence.

  5. Suspension of milking in dairy cows produces a transient increase in milk lactoferrin concentration and yield after resumption of milking.

    PubMed

    Davis, S R; South, C R

    2015-11-01

    Lactoferrin is a multifunctional glycoprotein with a range of antimicrobial and immune-related properties that is found at >10-fold higher concentration in human milk (~1.7 g/L) relative to bovine milk (~0.15 g/L). Consumer demand is increasing for bovine lactoferrin through a wide range of nutritional and cosmetic consumer products. Increasing lactoferrin yield and concentration in bovine milk could assist in satisfying this increasing demand and may also help in increasing resistance to bovine mammary infection. Two experiments with cows in mid and late lactation were carried out to examine milking strategies to increase milk lactoferrin concentration and yield. Milking was suspended in cows normally milked twice daily, for periods of 2, 4, or 7d (mid lactation) or 2 or 4d (late lactation) after which cows were milked out and twice-daily milking resumed for 4d. In all groups, lactoferrin concentration was significantly increased during the remilking period, approaching concentrations similar to those found in human milk (~1 g/L). Lactoferrin yields were significantly higher in all treatment groups, although increasing the nonmilking period beyond 2d offered no advantage. Milk yield was lower initially after resumption of milking but recovered to preexperimental values by the fourth day of remilking in all groups, except the 4-d nonmilking group in late lactation. Milk somatic cell count was significantly elevated in all groups at the start of remilking but had substantially reduced by d 4 and reached a preexperimental level in the 2-d nonmilking group of mid-lactation cows. In summary, extended milking intervals can be used as a tool to produce a short-term increase in the concentration and yield of lactoferrin from bovine milk during established lactation, without any apparent long-term effects on milk yield and quality.

  6. Role of transiently altered sarcolemmal membrane permeability and basic fibroblast growth factor release in the hypertrophic response of adult rat ventricular myocytes to increased mechanical activity in vitro.

    PubMed Central

    Kaye, D; Pimental, D; Prasad, S; Mäki, T; Berger, H J; McNeil, P L; Smith, T W; Kelly, R A

    1996-01-01

    One of the trophic factors that has been implicated in initiating or facilitating growth in response to increased mechanical stress in several tissues and cell types is basic fibroblast growth factor (bFGF; FGF-2). Although mammalian cardiac muscle cells express bFGF, it is not known whether it plays a role in mediating cardiac adaptation to increased load, nor how release of the cytosolic 18-kD isoform of bFGF would be regulated in response to increased mechanical stress. To test the hypothesis that increased mechanical activity induces transient alterations in sarcolemmal permeability that allow cytosolic bFGF to be released and subsequently to act as an autocrine and paracrine growth stimulus, we examined primary isolates of adult rat ventricular myocytes maintained in serum-free, defined medium that were continually paced at 3 Hz for up to 5 d. Paced myocytes, but not nonpaced control cells, exhibited a "hypertrophic" response, which was characterized by increases in the rate of phenylalanine incorporation, total cellular protein content, and cell size. These changes could be mimicked in control cells by exogenous recombinant bFGF and could be blocked in continually paced cells by a specific neutralizing anti-bFGF antibody. In addition, medium conditioned by continually paced myocytes contained significantly more bFGF measured by ELISA and more mitogenic activity for 3T3 cells, activity that could be reduced by a neutralizing anti-bFGF antibody. The hypothesis that transient membrane disruptions sufficient to allow release of cytosolic bFGF occur in paced myocytes was examined by monitoring the rate of uptake into myocytes from the medium of 10-kD dextran linked to fluorescein. Paced myocytes exhibited a significantly higher rate of fluoresceinlabeled dextran uptake. These data are consistent with the hypothesis that nonlethal, transient alterations in sarcolemmal membrane permeability with release of cytosolic bFGF is one mechanism by which increased

  7. In vitro effects of quercetin on oxidative stress mediated in human erythrocytes by benzoic acid and citric acid.

    PubMed

    Baş, Hatice; Kalender, Suna; Pandir, Dilek

    2014-01-01

    Benzoic acid (BA) and citric acid (CA) are food additives commonly used in many food products. Food additives play an important role in food supply but they can cause various harmful effects. The in vitro adverse effects of BA and CA and the protective effect of quercetin on human erythrocytes were investigated by measuring malondialdehyde (MDA) levels and superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione-S-transferase (GST) activities. Erythrocytes were incubated with BA and CA, at three doses of 50, 100 and 200 microg/ml, and quercetin, at a concentration of 10 microM. After BA and CA application, a dose-dependent increase in MDA level and decreases in SOD, CAT, GST and GPx activities were found in erythrocytes. Among the two food additives, BA exerted a more harmful influence on human erythrocytes than CA. The protective effects of quercetin against oxidative stress--induction in the human erythrocytes by CA and BA, were found when these two food additives were applied at each of three doses of 50, 100 and 200 microg/ml. However, complete protection of quercetin against CA toxicity was only observed when this agent was applied at a lower dose of 50 microg/ml. Quercetin did not completely protect erythrocytes even at the lowest concentration of BA.

  8. [Study of quantum-pharmacological chemical characteristics of quercetin].

    PubMed

    Zahorodnyĭ, M I

    2007-01-01

    It was established in the previous studies that quercetin prevented the development and caused faster regression of ulcers, petechia and anabroses in rats, which were induced by diclofenac taking. In the group of patients taking diclofenac together with quercetin, the ulcers and dyspeptic events were less found. The application of quercetin normalizes the function and metabolism of cartilage tissue of rabbits with an experimental osteoarthrosis and in patients with osteoartrosis. Quantum-chemical properties of molecule quercetin were studied using the methods of molecular mechanics MM+ and ab initio 6-31G*, and also semiempirical method. The following indices were investigated: distance between atoms (A), the distribution of electronic density of only external valency electrons, distribution of electrostatic potential; common energy of the exertion of molecule (kkal/mmol); binding energy (kkal/mmol); electron energy (kkal/mmol); energy of nucleus-nucleus interaction (kkal/mmol); formation heat (kkal/mmol); atomic charge (eB); value of the dipole moment of molecule (D); localization and energy of highest occupied orbital (HOMO) and the lowest unoccupied (LUMO) molecular orbital (eB) of quercetin miolecule; the value of absolute rigidity of chemical structure of bioflavonoid. It was shown, that bioflavonoid quercetin belongs to mild reagents, has nucleophilic properties, can react with alkaline, unsaturated and aromatic compounds,. Polar substitutes in the quercetine molecule influence on the distribution of superficial valency electrons and localization of HOMO and LUMO. The energy value of quercetin LUMO enables us to refer quercetine to the reducing agent and it is illustrated by antioxidant properties of this medicine. PMID:18663944

  9. Quercetin for chronic prostatitis/chronic pelvic pain syndrome.

    PubMed

    Shoskes, Daniel A; Nickel, J Curtis

    2011-08-01

    Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common condition with a heterogeneous origin that responds best to multimodal therapy. The bioflavonoid quercetin has antioxidant and antiinflammatory effects that have proven useful for treating this condition. Using the clinical phenotype system UPOINT, quercetin can be helpful for those with organ-specific complaints (bladder or prostate) and pelvic floor spasm. This article discusses the current understanding of CP/CPPS and how treatment with quercetin can be used alone or as part of multimodal therapy.

  10. The Attentional Boost Effect: Transient Increases in Attention to One Task Enhance Performance in a Second Task

    ERIC Educational Resources Information Center

    Swallow, Khena M.; Jiang, Yuhong V.

    2010-01-01

    Recent work on event perception suggests that perceptual processing increases when events change. An important question is how such changes influence the way other information is processed, particularly during dual-task performance. In this study, participants monitored a long series of distractor items for an occasional target as they…

  11. Rutin (quercetin rutinoside) induced protein-energy malnutrition in chronic kidney disease, but quercetin acted beneficially.

    PubMed

    Hsieh, Chiu-Lan; Peng, Chiung-Chi; Chen, Kuan-Chou; Peng, Robert Y

    2013-07-31

    Nutraceutically, much of the literature has indicated that an aglycon and its related glycoside would act similarly. However, controversial reports are accumulating. We hypothesize that rutin (RT) and quercetin (QT) pharmacodynamically could act differently. To confirm this, doxorubicin (DR) (8.5 mg/kg) was used to induce rat chronic kidney disease (CKD) and then treated with QT and RT (each 70 mg/kg body weight per day) for 13 weeks. QT exhibited better body weight gaining effect (420 ± 45) vs RT, 350 ± 57 g/rat (p < 0.001). DR raised the ratio kidney-to-body weight (%) to 0.82 (p < 0.001) vs RT, 0.62 (p < 0.01), and QT, 0.35 (p < 0.01). DR reduced the glomerular filtration rate to 25.2 vs RT, 48 ± 11.3; QT, 124.7 ± 12.8 (p < 0.001) and the control, 191.5 ± 15.7 mL/h (p < 0.001). DRCKD reduced hematocrit to 29 ± 5; RT, to 28 ± 5 (p < 0.05); QT, to 36 ± 6 vs the control 37.5 ± 4%, (p < 0.01). DRCKD reduced the serum albumin (s-Ab) to 2.1 ± 0.2 (p < 0.001); QT, to 2.7 ± 0.2 (p < 0.05) vs the normal 4.3 ± 0.5 g/dL, yet RT was totally ineffective. DRCKD raised serum cholesterol level to 340 ± 30; vs RT, 260 ± 12; QT, 220 ± 25; and the normal value, 70 ± 25 mg/dL. DRCKD increased serum triglyceride to 260 ± 15 (p < 0.001), RT and QT restored it to 170 ± 25 and 200 ± 15 (p < 0.05) vs the normal 26-145 mg/dL. DRCKD elevated blood urea nitrogen to 38 ± 3 vs RT, to 98 ± 6 mg/dL (p < 0.001), implicating "protein-energy malnutrition". RT stimulated serum creatinine (sCr) production to reach 6.0 ± 0.9 mg/dL (p < 0.001). QT did not alter the sCr level. RT but not QT induced uremia and hypercreatininemia. DR significantly downregulated Bcl-2, but highly upregulated Bax, Bad, and cleaved caspase-3, implicating the intrinsic mitochondrial pathway. DR damaged DNA, but QT completely rescued such an effect and recovered renal amyloidosis and collagen deposition. Conclusively, RT and QT act differently, and RT is inferior to QT with respect to treating CKD.

  12. Response to CO{sub 2} transient increase in the GISS coupled model: Regional coolings in a warming climate

    SciTech Connect

    Russell, G.L.; Rind, D.

    1999-02-01

    The GISS coupled atmosphere-ocean model is used to investigate the effect of increased atmospheric CO{sub 2} by comparing a compounded 1% CO{sub 2} increase experiment with a control simulation. After 70 yr of integration, the global surface air temperature in the 1% CO{sub 2} experiment is 1.43 C warmer. In spite of this global warming, there are two distinct regions, the northern Atlantic Ocean and the southern Pacific Ocean, where the surface air temperature is up to 4 C cooler. This situation is maintained by two positive feedbacks: a local effect on convection in the South Pacific and a nonlocal impact on the meridional circulation in the North Atlantic. The poleward transport of latent energy and dry static energy by the atmosphere is greater in the 1% CO{sub 2} experiment, caused by warming and therefore increased water vapor and greater greenhouse capacity at lower latitudes. The larger atmospheric transports tend to reduce upward vertical fluxes of heat and moisture from the ocean surface at high latitudes, which has the effect of stabilizing the ocean, reducing both convection and the thermohaline circulation. With less convection, less warm water is brought up from below, and with a reduced North Atlantic thermohaline circulation, the poleward energy transport by the oceans decreases. The colder water then leads to further reductions in evaporation, decreases of salinity at high latitudes, continued stabilization of the ocean, and maintenance of reduced convection and meridional overturning. Although sea ice decreases globally, it increases in the cooling regions, which reduces the overall climate sensitivity, especially in the Southern Hemisphere. Tropical warming has been observed over the past several decades; if modeling studies such as this and others that have produced similar effects are valid, these processes may already be beginning.

  13. Response to CO2 Transient Increase in the GISS Coupled Model: Regional Coolings in a Warming Climate

    NASA Technical Reports Server (NTRS)

    Russell, Gary L.; Rind, David

    1999-01-01

    The (GISS) Goddard Institute for Space Studies coupled atmosphere-ocean model is used to investigate the effect of increased atmospheric CO2 by comparing a compounded 1 percent CO2 increase experiment with a control simulation. After 70 years of integration, the global surface air temperature in the 1 percent CO2 experiment is 1.43 C warmer. In spite of this global warming, there are two distinct regions, the northern Atlantic Ocean and the southern Pacific Ocean, where the surface air temperature is up to 4 C cooler. This situation is maintained by two positive feedbacks: a local effect on convection in the South Pacific and a non-local impact on the meridional circulation in the North Atlantic. The poleward transport of latent energy and dry static energy by the atmosphere is greater in the 1 percent CO2 experiment, caused by warming and therefore increased water vapor and greater greenhouse capacity at lower latitudes. The larger atmospheric transports tend to reduce upward vertical fluxes of heat and moisture from the ocean surface at high latitudes, which has the effect of stabilizing the ocean, reducing both convection and the thermohaline circulation. With less convection, less warm water is brought up from below, and with a reduced North Atlantic thermohaline circulation (by 30 percent at time of CO2 doubling), the poleward energy transport by the oceans decreases. The colder water then leads to further reductions in evaporation, decreases of salinity at high latitudes, continued stabilization of the ocean, and maintenance of reduced convection and meridional overturning. Although sea ice decreases globally, it increases in the cooling regions which reduces the overall climate sensitivity; its effect is most pronounced in the Southern Hemisphere. Tropical warming has been observed over the past several decades; if modeling studies such as this and others which have produced similar effects are valid, these processes may already be beginning.

  14. Anti-inflammatory Effect of Mesenchymal Stromal Cell Transplantation and Quercetin Treatment in a Rat Model of Experimental Cerebral Ischemia.

    PubMed

    Zhang, Lan-Lan; Zhang, Hong-Tian; Cai, Ying-Qian; Han, Yan-Jiang; Yao, Fang; Yuan, Zhao-Hu; Wu, Bing-Yi

    2016-10-01

    Here, we have investigated the synergistic effect of quercetin administration and transplantation of human umbilical cord mesenchymal stromal cells (HUMSCs) following middle cerebral artery occlusion in rat. Combining quercetin treatment with delayed transplantation of HUMSCs after local cerebral ischemia significantly (i) improved neurological functional recovery; (ii) reduced proinflammatory cytokines (interleukin(IL)-1β and IL-6), increased anti-inflammatory cytokines (IL-4, IL-10, and transforming growth factor-β1), and reduced ED-1 positive areas; (iii) inhibited cell apoptosis (caspase-3 expression); and (iv) improved the survival rate of HUMSCs in the injury site. Altogether, our results demonstrate that combined HUMSC transplantation and quercetin treatment is a potential strategy for reducing secondary damage and promoting functional recovery following cerebral ischemia.

  15. Transient Increase of Retinal Nerve Fiber Layer Thickness after Vitrectomy with ILM Peeling for Idiopathic Macular Hole

    PubMed Central

    Sato, Atsuko; Senda, Nami; Fukui, Emi

    2016-01-01

    Purpose. The purpose of this study was to determine the long-term changes in the circumpapillary retinal nerve fiber layer (RNFL) thickness following macular hole surgery with internal limiting membrane (ILM) peeling combined with phacoemulsification. Methods. Thirty-eight eyes of 37 patients who had pars plana vitrectomy (n = 36) between 2010 and 2014 were studied. The average thicknesses of the global and the six sectors of the RNFL were determined before and at 1, 3, 6, 12, and 24 (n = 22) months (M) after the surgery by spectral-domain optical coherent tomography. The postoperative mean RNFL thickness at each time was compared to that before the surgery by paired t-tests. Results. The RNFL of the operated eyes was significantly thicker at 1 month (1 M) and 3 M in all but the inferior-nasal sectors. The significant increase remained until 12 M in the superior-temporal and superior-nasal sectors. In addition, the RNFL was also significantly thicker in the temporal-inferior sector at 12 M based on the findings in 38 eyes. Conclusions. The postoperative RNFL was thicker in all but the nasal-inferior sector for at least 12 M after surgery. This prolonged increase of the RNFL thickness may indicate damage and mild edema of the RNFL. PMID:27803812

  16. Aging of TiO2 Nanoparticles Transiently Increases Their Toxicity to the Pelagic Microcrustacean Daphnia magna.

    PubMed

    Seitz, Frank; Lüderwald, Simon; Rosenfeldt, Ricki R; Schulz, Ralf; Bundschuh, Mirco

    2015-01-01

    During their aquatic life cycle, nanoparticles are subject to environmentally driven surface modifications (e.g. agglomeration or coating) associated with aging. Although the ecotoxicological potential of nanoparticles might be affected by these processes, only limited information about the potential impact of aging is available. In this context, the present study investigated acute (96 h) and chronic (21 d) implications of systematically aged titanium dioxide nanoparticles (nTiO2; ~90 nm) on the standard test species Daphnia magna by following the respective test guidelines. The nTiO2 were aged for 0, 1, 3 and 6 d in media with varying ionic strengths (Milli-Q water: approx. 0.00 mmol/L and ASTM: 9.25 mmol/L) in the presence or absence of natural organic matter (NOM). Irrespective of the other parameters, aging in Milli-Q did not change the acute toxicity relative to an unaged control. In contrast, 6 d aged nTiO2 in ASTM without NOM caused a fourfold decreased acute toxicity. Relative to the 0 d aged particles, nTiO2 aged for 1 and 3 d in ASTM with NOM, which is the most environmentally-relevant setup used here, significantly increased acute toxicity (by approximately 30%), while a toxicity reduction (60%) was observed for 6 d aged nTiO2. Comparable patterns were observed during the chronic experiments. A likely explanation for this phenomenon is that the aging of nTiO2 increases the particle size at the start of the experiment or the time of the water exchange from <100 nm to approximately 500 nm, which is the optimal size range to be taken up by filter feeding D. magna. If subjected to further agglomeration, larger nTiO2 particles, however, cannot be retained by the daphnids' filter apparatus ultimately reducing their ecotoxicological potential. This non-linear pattern of increasing and decreasing nTiO2 related toxicity over the aging duration, highlights the knowledge gap regarding the underlying mechanisms and processes. This understanding seems, however

  17. Aging of TiO2 Nanoparticles Transiently Increases Their Toxicity to the Pelagic Microcrustacean Daphnia magna.

    PubMed

    Seitz, Frank; Lüderwald, Simon; Rosenfeldt, Ricki R; Schulz, Ralf; Bundschuh, Mirco

    2015-01-01

    During their aquatic life cycle, nanoparticles are subject to environmentally driven surface modifications (e.g. agglomeration or coating) associated with aging. Although the ecotoxicological potential of nanoparticles might be affected by these processes, only limited information about the potential impact of aging is available. In this context, the present study investigated acute (96 h) and chronic (21 d) implications of systematically aged titanium dioxide nanoparticles (nTiO2; ~90 nm) on the standard test species Daphnia magna by following the respective test guidelines. The nTiO2 were aged for 0, 1, 3 and 6 d in media with varying ionic strengths (Milli-Q water: approx. 0.00 mmol/L and ASTM: 9.25 mmol/L) in the presence or absence of natural organic matter (NOM). Irrespective of the other parameters, aging in Milli-Q did not change the acute toxicity relative to an unaged control. In contrast, 6 d aged nTiO2 in ASTM without NOM caused a fourfold decreased acute toxicity. Relative to the 0 d aged particles, nTiO2 aged for 1 and 3 d in ASTM with NOM, which is the most environmentally-relevant setup used here, significantly increased acute toxicity (by approximately 30%), while a toxicity reduction (60%) was observed for 6 d aged nTiO2. Comparable patterns were observed during the chronic experiments. A likely explanation for this phenomenon is that the aging of nTiO2 increases the particle size at the start of the experiment or the time of the water exchange from <100 nm to approximately 500 nm, which is the optimal size range to be taken up by filter feeding D. magna. If subjected to further agglomeration, larger nTiO2 particles, however, cannot be retained by the daphnids' filter apparatus ultimately reducing their ecotoxicological potential. This non-linear pattern of increasing and decreasing nTiO2 related toxicity over the aging duration, highlights the knowledge gap regarding the underlying mechanisms and processes. This understanding seems, however

  18. Aging of TiO2 Nanoparticles Transiently Increases Their Toxicity to the Pelagic Microcrustacean Daphnia magna

    PubMed Central

    Seitz, Frank; Lüderwald, Simon; Rosenfeldt, Ricki R.; Schulz, Ralf; Bundschuh, Mirco

    2015-01-01

    During their aquatic life cycle, nanoparticles are subject to environmentally driven surface modifications (e.g. agglomeration or coating) associated with aging. Although the ecotoxicological potential of nanoparticles might be affected by these processes, only limited information about the potential impact of aging is available. In this context, the present study investigated acute (96 h) and chronic (21 d) implications of systematically aged titanium dioxide nanoparticles (nTiO2; ~90 nm) on the standard test species Daphnia magna by following the respective test guidelines. The nTiO2 were aged for 0, 1, 3 and 6 d in media with varying ionic strengths (Milli-Q water: approx. 0.00 mmol/L and ASTM: 9.25 mmol/L) in the presence or absence of natural organic matter (NOM). Irrespective of the other parameters, aging in Milli-Q did not change the acute toxicity relative to an unaged control. In contrast, 6 d aged nTiO2 in ASTM without NOM caused a fourfold decreased acute toxicity. Relative to the 0 d aged particles, nTiO2 aged for 1 and 3 d in ASTM with NOM, which is the most environmentally-relevant setup used here, significantly increased acute toxicity (by approximately 30%), while a toxicity reduction (60%) was observed for 6 d aged nTiO2. Comparable patterns were observed during the chronic experiments. A likely explanation for this phenomenon is that the aging of nTiO2 increases the particle size at the start of the experiment or the time of the water exchange from <100 nm to approximately 500 nm, which is the optimal size range to be taken up by filter feeding D. magna. If subjected to further agglomeration, larger nTiO2 particles, however, cannot be retained by the daphnids’ filter apparatus ultimately reducing their ecotoxicological potential. This non-linear pattern of increasing and decreasing nTiO2 related toxicity over the aging duration, highlights the knowledge gap regarding the underlying mechanisms and processes. This understanding seems, however

  19. Chemoprevention studies of the flavonoids quercetin and rutin in normal and azoxymethane-treated mouse colon.

    PubMed

    Yang, K; Lamprecht, S A; Liu, Y; Shinozaki, H; Fan, K; Leung, D; Newmark, H; Steele, V E; Kelloff, G J; Lipkin, M

    2000-09-01

    In this study we investigated the chemopreventive effects of quercetin and rutin when added to standard AIN-76A diet and fed to normal and azoxymethane (AOM)-treated mice. Early changes in colonic mucosa were analyzed, including colonic cell proliferation, apoptotic cell death, cyclin D(1) expression and focal areas of dysplasia (FAD). The findings show that the number of colonic epithelial cells per crypt column increased (P: < 0.01) in each normal mouse group fed the flavonoids; AOM administration increased colonic crypt cell proliferation and resulted in a marked rise of bromodeoxyuridine-labeled cells in the lower proliferative zone of the crypt. Both supplementary dietary quercetin and rutin increased the apoptotic index and caused a redistribution of apoptotic cells along the crypt axis in normal mice fed a standard AIN-76A diet. The number of apoptotic cells/column and apoptotic indices markedly increased (P: < 0.01) in the AOM-treated group compared with untreated animals; apoptotic cells expanded throughout the colonic crypts after flavonoid supplementation and AOM administration. Positive cyclin D(1) expression was detected in mice on diets supplemented either with quercetin (P: < 0.01) or rutin (P: < 0.05). AOM administration resulted in the formation of FAD. Both the number of mice exhibiting FAD and the total numer of FAD observed were significantly reduced (P: < 0.01) in AOM-treated animals fed flavonoids compared with mice maintained on the standard AIN-76A diet. Surprisingly, however, quercetin alone was able to induce FAD in 22% of normal mice fed the standard AIN-76A diet.

  20. Interleukin-1 administration before lethal irradiation and allogeneic bone marrow transplantation: early transient increase of peripheral granulocytes and successful engraftment with accelerated leukocyte, erythrocyte, and platelet recovery.

    PubMed

    Tiberghien, P; Laithier, V; Mabed, M; Racadot, E; Reynolds, C W; Angonin, R; Loumi, R; Pavy, J J; Cahn, J Y; Noir, A

    1993-04-01

    Administration of interleukin-1 beta (IL-1 beta) before a lethal irradiation with or without allogeneic bone marrow transplantation (BMT) protects greater than 90% of the irradiated mice. To approach the mechanisms responsible for the radioprotective effect of IL-1, we examined the effects of IL-1 pretreatment on engraftment and kinetics of peripheral blood, spleen, and marrow cell reconstitution after irradiation and BMT. Although the BMT was not necessary for the survival of the IL-1-pretreated lethally irradiated mice, allogeneic marrow did engraft in these mice as evaluated in the spleen and marrow 2 months after BMT. IL-1 pretreatment significantly accelerated hematopoietic recovery versus transplanted saline-treated controls with a pronounced enhancement of peripheral leukocyte, platelet, and erythrocyte recovery. Leukocyte recovery in IL-1-pretreated mice was unique in that IL-1 first induced an early transient (maximum at day 7) increase of peripheral granulocytes before accelerating leukocyte recovery after day 11. IL-1 pretreatment also significantly enhanced marrow cell recovery after allogeneic BMT with an eightfold increase in marrow cellularity from day 4 to 11 versus control transplanted mice. When lethal irradiation was not followed by allogeneic BMT. IL-1 pretreatment also affected the peripheral reconstitution of leukocytes, platelets, and erythrocytes. Interestingly, in the absence of BMT, IL-1 also induced an early circulation of peripheral granulocytes. Overall, our data demonstrate that a single administration of IL-1 before lethal irradiation and allogeneic BMT can induce an early transient increase of circulating granulocytes, followed by an accelerated multilineage recovery and long-term allogeneic engraftment. PMID:8461477

  1. Protective effects of quercetin during influenza virus-induced oxidative stress.

    PubMed

    Raju, T A; Lakshmi, A N; Anand, T; Rao, L V; Sharma, G

    2000-12-01

    Oxidative stress was found to have a role in many viral diseases including AIDS, hepatitis and influenza. In the present study the pathology of influenza viral infection in the lungs, which may lead to oxidative stress, was investigated and an attempt was made to study the efficacy of anti-oxidants as therapeutic agents. Adult male mice of Swiss albino type were infected with influenza virus (A/Hong Kong/8/68) and studied for the antioxidant status in the lungs by evaluating the lung enzymatic anti-oxidant system including superoxide dismutase and catalase. Superoxide radical generation, which might increase by the activated alveolar macrophages, was estimated by nitroblue-tetrazolium reduction assay. We have also estimated lipid peroxidation levels in lung through thiobarbutiric acid reactive substances assay. We also examined the ability of flavonoid quercetin in protecting from influenza virus-induced oxidative stress. The influenza-infected group showed decreased levels of superoxide dismutase and catalase; however, anti-oxidant supplemented groups showed these activities to be the same as in the control group. The lipid peroxide levels were increased in virus-infected mice. Administration of quercetin lowered the lipid peroxide levels significantly. Formazan positive cells were increased by 80% in the virus-infected group and supplementation with quercetin reduced their number to 44%.

  2. Differential effects of quercetin on hippocampus-dependent learning and memory in mice fed with different diets related with oxidative stress.

    PubMed

    Xia, Shu-Fang; Xie, Zhen-Xing; Qiao, Yi; Li, Li-Rong; Cheng, Xiang-Rong; Tang, Xue; Shi, Yong-Hui; Le, Guo-Wei

    2015-01-01

    High fat diets induce oxidative stress which may be involved in neurodegenerative diseases. Quercetin is a kind of antioxidant that has neuroprotective effects and potent7ial pro-oxidant effects as well. In this study, we evaluated cognitive function in mice fed with high fat diets and basic diets with or without quercetin. Male Chinese Kunming (KM) mice were randomly assigned to five groups fed with basic diet (Control), basic diet with 0.005% (w/w) quercetin (CQ1), high fat diet (HFD), HFD with 0.005% (w/w) quercetin (HFDQ1) and 0.01% (w/w) quercetin (HFDQ2) for 13weeks. At the end of the study period, fasting blood glucose (FBG), plasma and hippocampal markers of oxidative stress, plasma lipid status, Morris water maze as well as hippocampal relative mRNA expression of akt, bdnf, camkII, creb, gsk-3β, nrf2 and pi3k were examined. The results suggested that in comparison to the control group, the escape latency was increased and percent time spent in the target quadrant was decreased, with increased reactive carbonyls, malondialdehyde (MDA) and declined expression of pi3k, akt, nrf2, creb and bdnf in the hippocampus of HFD and CQ1 groups. Conversely, higher quercetin supplemented to HFD improved antioxidant capacity and reversed cognitive decline completely. Significant correlations between the redox status and cognition-related gene expression were observed as well (P<0.05). Thus, in the case of oxidative stress, an appropriate dose of quercetin can attenuate oxidative stress to improve hippocampus dependent cognition. But under a balanced situation, quercetin exerts pro-oxidant effects to impair cognition.

  3. Quercetin-3-methyl ether inhibits lapatinib-sensitive and -resistant breast cancer cell growth by inducing G(2)/M arrest and apoptosis.

    PubMed

    Li, Jixia; Zhu, Feng; Lubet, Ronald A; De Luca, Antonella; Grubbs, Clinton; Ericson, Marna E; D'Alessio, Amelia; Normanno, Nicola; Dong, Zigang; Bode, Ann M

    2013-02-01

    Lapatinib, an oral, small-molecule, reversible inhibitor of both EGFR and HER2, is highly active in HER2 positive breast cancer as a single agent and in combination with other therapeutics. However, resistance against lapatinib is an unresolved problem in clinical oncology. Recently, interest in the use of natural compounds to prevent or treat cancers has gained increasing interest because of presumed low toxicity. Quercetin-3-methyl ether, a naturally occurring compound present in various plants, has potent anticancer activity. Here, we found that quercetin-3-methyl ether caused a significant growth inhibition of lapatinib-sensitive and -resistant breast cancer cells. Western blot data showed that quercetin-3-methyl ether had no effect on Akt or ERKs signaling in resistant cells. However, quercetin-3-methyl ether caused a pronounced G(2)/M block mainly through the Chk1-Cdc25c-cyclin B1/Cdk1 pathway in lapatinib-sensitive and -resistant cells. In contrast, lapatinib produced an accumulation of cells in the G(1) phase mediated through cyclin D1, but only in lapatinib-sensitive cells. Moreover, quercetin-3-methyl ether induced significant apoptosis, accompanied with increased levels of cleaved caspase 3, caspase 7, and poly(ADP-ribose) polymerase (PARP) in both cell lines. Overall, these results suggested that quercetin-3-methyl ether might be a novel and promising therapeutic agent in lapatinib-sensitive or -resistant breast cancer patients. PMID:22086611

  4. Molecular Targets Underlying the Anticancer Effects of Quercetin: An Update.

    PubMed

    Khan, Fazlullah; Niaz, Kamal; Maqbool, Faheem; Ismail Hassan, Fatima; Abdollahi, Mohammad; Nagulapalli Venkata, Kalyan C; Nabavi, Seyed Mohammad; Bishayee, Anupam

    2016-08-29

    Quercetin, a medicinally important member of the flavonoid family, is one of the most prominent dietary antioxidants. It is present in a variety of foods-including fruits, vegetables, tea, wine, as well as other dietary supplements-and is responsible for various health benefits. Numerous pharmacological effects of quercetin include protection against diseases, such as osteoporosis, certain forms of malignant tumors, and pulmonary and cardiovascular disorders. Quercetin has the special ability of scavenging highly reactive species, such as hydrogen peroxide, superoxide anion, and hydroxyl radicals. These oxygen radicals are called reactive oxygen species, which can cause oxidative damage to cellular components, such as proteins, lipids, and deoxyribonucleic acid. Various oxygen radicals play important roles in pathophysiological and degenerative processes, such as aging. Subsequently, several studies have been performed to evaluate possible advantageous health effects of quercetin and to collect scientific evidence for these beneficial health claims. These studies also gather data in order to evaluate the exact mechanism(s) of action and toxicological effects of quercetin. The purpose of this review is to present and critically analyze molecular pathways underlying the anticancer effects of quercetin. Current limitations and future directions of research on this bioactive dietary polyphenol are also critically discussed.

  5. Molecular Targets Underlying the Anticancer Effects of Quercetin: An Update.

    PubMed

    Khan, Fazlullah; Niaz, Kamal; Maqbool, Faheem; Ismail Hassan, Fatima; Abdollahi, Mohammad; Nagulapalli Venkata, Kalyan C; Nabavi, Seyed Mohammad; Bishayee, Anupam

    2016-01-01

    Quercetin, a medicinally important member of the flavonoid family, is one of the most prominent dietary antioxidants. It is present in a variety of foods-including fruits, vegetables, tea, wine, as well as other dietary supplements-and is responsible for various health benefits. Numerous pharmacological effects of quercetin include protection against diseases, such as osteoporosis, certain forms of malignant tumors, and pulmonary and cardiovascular disorders. Quercetin has the special ability of scavenging highly reactive species, such as hydrogen peroxide, superoxide anion, and hydroxyl radicals. These oxygen radicals are called reactive oxygen species, which can cause oxidative damage to cellular components, such as proteins, lipids, and deoxyribonucleic acid. Various oxygen radicals play important roles in pathophysiological and degenerative processes, such as aging. Subsequently, several studies have been performed to evaluate possible advantageous health effects of quercetin and to collect scientific evidence for these beneficial health claims. These studies also gather data in order to evaluate the exact mechanism(s) of action and toxicological effects of quercetin. The purpose of this review is to present and critically analyze molecular pathways underlying the anticancer effects of quercetin. Current limitations and future directions of research on this bioactive dietary polyphenol are also critically discussed. PMID:27589790

  6. Molecular Targets Underlying the Anticancer Effects of Quercetin: An Update

    PubMed Central

    Khan, Fazlullah; Niaz, Kamal; Maqbool, Faheem; Ismail Hassan, Fatima; Abdollahi, Mohammad; Nagulapalli Venkata, Kalyan C.; Nabavi, Seyed Mohammad; Bishayee, Anupam

    2016-01-01

    Quercetin, a medicinally important member of the flavonoid family, is one of the most prominent dietary antioxidants. It is present in a variety of foods—including fruits, vegetables, tea, wine, as well as other dietary supplements—and is responsible for various health benefits. Numerous pharmacological effects of quercetin include protection against diseases, such as osteoporosis, certain forms of malignant tumors, and pulmonary and cardiovascular disorders. Quercetin has the special ability of scavenging highly reactive species, such as hydrogen peroxide, superoxide anion, and hydroxyl radicals. These oxygen radicals are called reactive oxygen species, which can cause oxidative damage to cellular components, such as proteins, lipids, and deoxyribonucleic acid. Various oxygen radicals play important roles in pathophysiological and degenerative processes, such as aging. Subsequently, several studies have been performed to evaluate possible advantageous health effects of quercetin and to collect scientific evidence for these beneficial health claims. These studies also gather data in order to evaluate the exact mechanism(s) of action and toxicological effects of quercetin. The purpose of this review is to present and critically analyze molecular pathways underlying the anticancer effects of quercetin. Current limitations and future directions of research on this bioactive dietary polyphenol are also critically discussed. PMID:27589790

  7. A Model for Mild Traumatic Brain Injury that Induces Limited Transient Memory Impairment and Increased Levels of Axon Related Serum Biomarkers

    PubMed Central

    Rostami, Elham; Davidsson, Johan; Ng, Kian Chye; Lu, Jia; Gyorgy, Andrea; Walker, John; Wingo, Daniel; Plantman, Stefan; Bellander, Bo-Michael; Agoston, Denes V.; Risling, Mårten

    2012-01-01

    Mild traumatic brain injury (mTBI) is one of the most common neuronal insults and can lead to long-term disabilities. mTBI occurs when the head is exposed to a rapid acceleration-deceleration movement triggering axonal injuries. Our limited understanding of the underlying pathological changes makes it difficult to predict the outcome of mTBI. In this study we used a scalable rat model for rotational acceleration TBI, previously characterized for the threshold of axonal pathology. We have analyzed whether a TBI just above the defined threshold would induce any detectable behavioral changes and/or changes in serum biomarkers. The effect of injury on sensory motor functions, memory and anxiety were assessed by beam walking, radial arms maze and elevated plus maze at 3–7 days following TBI. The only behavioral deficits found were transient impairments in working and reference memory. Blood serum was analyzed at 1, 3, and 14 days after injury for changes in selected protein biomarkers. Serum levels of neurofilament heavy chain and Tau, as well as S100B and myelin basic protein showed significant increases in the injured animals at all time points. No signs of macroscopic injuries such as intracerebral hematomas or contusions were found. Amyloid precursor protein immunostaining indicated axonal injuries at all time points analyzed. In summary, this model mimics some of the key symptoms of mTBI, such as transient memory impairment, which is paralleled by an increase in serum biomarkers. Our findings suggest that serum biomarkers may be used to detect mTBI. The model provides a suitable foundation for further investigation of the underlying pathology of mTBI. PMID:22837752

  8. Soothing and anti-itch effect of quercetin phytosome in human subjects: a single-blind study

    PubMed Central

    Maramaldi, Giada; Togni, Stefano; Pagin, Ivan; Giacomelli, Luca; Cattaneo, Roberta; Eggenhöffner, Roberto; Burastero, Samuele E

    2016-01-01

    Background We evaluated the ability of quercetin, a natural antioxidant formulated in a specific delivery system, to reduce skin inflammation induced by a variety of stimuli, including UV radiation, stimulation with a histamine solution, or contact with chemical irritants. In particular, we tested the soothing and anti-itch effect of Quercevita®, 1% cream for external use, a formulation characterized by a phospholipids-based delivery system. Patients and methods The study was a monocentric, single blind trial that enrolled a group of 30 healthy volunteers. The back of each subject was examined to identify four quadrants with no previous skin damage or naevi that were treated in order to induce a controlled and reversible form of skin stress. The areas were treated as follows: no product; Quercevita® 1% cream, 2 mg/cm2; placebo; positive control (a commercially available topical formulation containing 1% dexchlorpheniramine). Results Only quercetin phospholipids 1% and dexchlorpheniramine 1% achieved a significant reduction in erythema with comparable results: (–10.05% [P=0.00329] for quercetin phospholipids 1% vs –14.05% [P=0.00046] for the positive control). Moreover, quercetin phospholipids 1% and dexchlorpheniramine 1% were both associated with a significant decrease in mean wheal diameter: (–13.25% and –12.23% for dexchlorpheniramine 1%, respectively). Similar findings were reported for the other tested parameters. Conclusion Quercetin has a skin protective effect against damage caused by a variety of insults, including UV radiation, histamine, or contact with toxic chemical compounds. Indeed, quercetin is able to reduce redness, itching, and inflammation of damaged skin; it may also help restore skin barrier function, increasing hydration, and reducing water loss. PMID:27013898

  9. Development and optimization of quercetin-loaded PLGA nanoparticles by experimental design

    PubMed Central

    TEFAS, LUCIA RUXANDRA; TOMUŢĂ, IOAN; ACHIM, MARCELA; VLASE, LAURIAN

    2015-01-01

    Background and aims Quercetin is a flavonoid with good antioxidant activity, and exhibits various important pharmacological effects. The aim of the present work was to study the influence of formulation factors on the physicochemical properties of quercetin-loaded polymeric nanoparticles in order to optimize the formulation. Materials and methods The nanoparticles were prepared by the nanoprecipitation method. A 3-factor, 3-level Box-Behnken design was employed in this study considering poly(D,L-lactic-co-glycolic) acid (PLGA) concentration, polyvinyl alcohol (PVA) concentration and the stirring speed as independent variables. The responses were particle size, polydispersity index, zeta potential and encapsulation efficiency. Results The PLGA concentration seemed to be the most important factor influencing quercetin-nanoparticle characteristics. Increasing PLGA concentration led to an increase in particle size, as well as encapsulation efficiency. On the other hand, it exhibited a negative influence on the polydispersity index and zeta potential. The PVA concentration and the stirring speed had only a slight influence on particle size and polydispersity index. However, PVA concentration had an important negative effect on the encapsulation efficiency. Based on the results obtained, an optimized formulation was prepared, and the experimental values were comparable to the predicted ones. Conclusions The overall results indicated that PLGA concentration was the main factor influencing particle size, while entrapment efficiency was predominantly affected by the PVA concentration. PMID:26528074

  10. Colon-targeted quercetin delivery using natural polymer to enhance its bioavailability

    PubMed Central

    Singhal, Anil; Jain, H.; Singhal, Vipin; Elias, Edwin J.; Showkat, Ahmad

    2011-01-01

    The aim of the present study is to develop a polymer (Guar Gum)-based matrix tablet (using quercetin as a model drug) with sufficient mechanical strength, and promising in vitro mouth-to-colon release profile. By definition, an oral colonic delivery system should retard drug release in the stomach and small intestine, and allow complete release in the colon. By drug delivery to the colon would therefore ensure direct treatment at the disease site, lower dosing, and fewer systemic side effects. Quercetin is antioxidant in nature and used to treat colon cancer, but they have poor absorption in the upper part of the gastrointestinal tract (GIT). As a site for drug delivery, the colon offers a near neutral pH, reduced digestive enzymatic activity, a long transit time, and an increased responsiveness to absorption enhancers. By achieving a colon-targeted drug delivery system, the absorption of quercetin may be increased, which leads to better bioactivity in fewer doses. PMID:21731393

  11. Studies on the effect of quercetin and nitrates on the redox homeostasis using in vitro model.

    PubMed

    Kurzeja, Ewa; Stec, Małgorzata; Synowiec-Wojtarowicz, Agnieszka; Jowsa, Andrzej; Pawłowska-Góral, Katarzyna

    2014-07-01

    Antioxidants are widely considered to be a preventive measure for many diseases and beneficial for health. However, an increasing number of reports suggest a lack of any influence by antioxidants on health or even harmful pro-oxidative effects of antioxidants. In most cases, the research was conducted with respect to a chosen antioxidant, without considering the presence of other chemical substances present in food, with which these compounds may react. The aim of this work was to determine whether and to what extent the simultaneous presence of quercetin and sodium nitrate influences oxidative-reductive homeostasis in fibroblast cultures. Superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), and nitric oxide synthase (NOS) activities were measured together with nitric oxide (NO) concentration and total antioxidant status (TAS). An increase in the activity of all the enzymes measured and in the NO concentration was determined compared with the control culture. The most prominent changes were observed at the highest quercetin concentration. These results indicate that the simultaneous presence of quercetin and sodium nitrate disrupts the oxidative-reductive homeostasis in fibroblasts.

  12. Pioglitazone, quercetin and hydroxy citric acid effect on hepatic biomarkers in Non Alcoholic Steatohepatitis

    PubMed Central

    Surapaneni, Krishna Mohan; Jainu, Mallika

    2014-01-01

    Background: Non alcoholic steatohepatitis (NASH), severe form of diseases belonging to the spectrum of the Non alcoholic fatty liver disease (NAFLD). It is an asymptomatic disease which leads to fibrosis and finally to cirrhosis, an end stage liver disease. Objective: To study the effect of pioglitazone, quercetin and hydroxy citric acid on hepatic biomarkers and various biochemical parameters in experimentally induced non alcoholic steatohepatitis (NASH). Materials and Methods: Male Wister rats were divided into 8 groups. The activities of alkaline phosphatase (ALP), aspartate transaminase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH) and γ-Glutamyl Transferase (GGT) were assayed in serum. The levels of various other biochemical parameters such as serum albumin, total bilirubin, creatinine, urea, uric acid and glucose were also estimated in experimental NASH. Results: The NASH group produced severe liver injury by significantly increasing the serum levels of ALT, AST, GGT and LDH compared with that of the control. However, the experimental NASH rats treated with pioglitazone, with quercetin and with hydroxy citric acid showed an obvious decrease in ALT, AST, GGT and LDH levels when compared with that of NASH induced group. A significant increase in the levels of albumin, creatinine, urea, uric acid, glucose and total bilirubin was noticed in experimentally induced NASH group (group 2) when compared to rats in control group (group 1). Conclusion: It could be inferred from this study that, pioglitazone, quercetin and hydroxy citric acid may afford protection to the liver against NASH, as evidenced by the results of this study on the levels of various biochemical parameters such as glucose, urea, uric acid, creatinine and bilirubin. Whereas from the results of hepatic marker enzymes, it is evident that optimal protection was observed after quercetin treatment against experimental NASH whereas pioglitazone and hydroxy citric acid also confers

  13. Quercetin reduces eIF2α phosphorylation by GADD34 induction.

    PubMed

    Hayakawa, Miki; Itoh, Masanori; Ohta, Kazunori; Li, Shimo; Ueda, Masashi; Wang, Miao-xing; Nishida, Emika; Islam, Saiful; Suzuki, Chihiro; Ohzawa, Kaori; Kobori, Masuko; Inuzuka, Takashi; Nakagawa, Toshiyuki

    2015-09-01

    The production of amyloid β (Aβ) in the brain from Aβ precursor protein (APP) through γ-secretase is important for the pathogenesis of Alzheimer's disease (AD). Our previous studies have demonstrated that autophagy impairment and endoplasmic reticulum stress increase presenilin 1 expression and enhance γ-secretase activity through the phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) and the translation of activating transcription factor 4 (ATF4). However, the inhibitory molecules for γ-secretase are largely unknown. Here, we demonstrate that the levels of ATF4 expression are increased in the brain of APP23 AD model mice; furthermore, these levels enhanced in the brain of APP23 mice crossed with obese and diabetic db/db (Lepr(db/db)) mice. A polyhydroxylated flavonoid, quercetin, suppressed presenilin 1 expression and Aβ secretion in autophagy-impaired cells by the induction of growth arrest and DNA damaged-inducible gene (GADD) 34, which mediates eIF2α dephosphorylation, leading to decreased ATF4 expression. GADD34 induction was observed in the brain of wild-type mice, and APP23 mice fed quercetin in their diet. After the long-term feeding of quercetin, deterioration in memory assessed by freezing behavior was delayed in APP23 mice. These results indicate that quercetin may reduce eIF2α phosphorylation and ATF4 expression through GADD34 induction in the brain, leading to the improvement of memory in aged mice and the delay of deterioration in memory at the early stage of AD in AD model mice. PMID:26070242

  14. 56Fe particle exposure results in a long-lasting increase in a cellular index of genomic instability and transiently suppresses adult hippocampal neurogenesis in vivo

    NASA Astrophysics Data System (ADS)

    DeCarolis, Nathan A.; Rivera, Phillip D.; Ahn, Francisca; Amaral, Wellington Z.; LeBlanc, Junie A.; Malhotra, Shveta; Shih, Hung-Ying; Petrik, David; Melvin, Neal R.; Chen, Benjamin P. C.; Eisch, Amelia J.

    2014-07-01

    The high-LET HZE particles from galactic cosmic radiation pose tremendous health risks to astronauts, as they may incur sub-threshold brain injury or maladaptations that may lead to cognitive impairment. The health effects of HZE particles are difficult to predict and unfeasible to prevent. This underscores the importance of estimating radiation risks to the central nervous system as a whole as well as to specific brain regions like the hippocampus, which is central to learning and memory. Given that neurogenesis in the hippocampus has been linked to learning and memory, we investigated the response and recovery of neurogenesis and neural stem cells in the adult mouse hippocampal dentate gyrus after HZE particle exposure using two nestin transgenic reporter mouse lines to label and track radial glia stem cells (Nestin-GFP and Nestin-CreERT2/R26R:YFP mice, respectively). Mice were subjected to 56Fe particle exposure (0 or 1 Gy, at either 300 or 1000 MeV/n) and brains were harvested at early (24 h), intermediate (7 d), and/or long time points (2-3 mo) post-irradiation. 56Fe particle exposure resulted in a robust increase in 53BP1+ foci at both the intermediate and long time points post-irradiation, suggesting long-term genomic instability in the brain. However, 56Fe particle exposure only produced a transient decrease in immature neuron number at the intermediate time point, with no significant decrease at the long time point post-irradiation. 56Fe particle exposure similarly produced a transient decrease in dividing progenitors, with fewer progenitors labeled at the early time point but equal number labeled at the intermediate time point, suggesting a recovery of neurogenesis. Notably, 56Fe particle exposure did not change the total number of nestin-expressing neural stem cells. These results highlight that despite the persistence of an index of genomic instability, 56Fe particle-induced deficits in adult hippocampal neurogenesis may be transient. These data support

  15. (56)Fe Particle Exposure Results in a Long-Lasting Increase in a Cellular Index of Genomic Instability and Transiently Suppresses Adult Hippocampal Neurogenesis in Vivo.

    PubMed

    DeCarolis, Nathan A; Rivera, Phillip D; Ahn, Francisca; Amaral, Wellington Z; LeBlanc, Junie A; Malhotra, Shveta; Shih, Hung-Ying; Petrik, David; Melvin, Neal; Chen, Benjamin P C; Eisch, Amelia J

    2014-07-01

    The high-LET HZE particles from galactic cosmic radiation pose tremendous health risks to astronauts, as they may incur sub-threshold brain injury or maladaptations that may lead to cognitive impairment. The health effects of HZE particles are difficult to predict and unfeasible to prevent. This underscores the importance of estimating radiation risks to the central nervous system as a whole as well as to specific brain regions like the hippocampus, which is central to learning and memory. Given that neurogenesis in the hippocampus has been linked to learning and memory, we investigated the response and recovery of neurogenesis and neural stem cells in the adult mouse hippocampal dentate gyrus after HZE particle exposure using two nestin transgenic reporter mouse lines to label and track radial glia stem cells (Nestin-GFP and Nestin-CreER(T2)/R26R:YFP mice, respectively). Mice were subjected to (56)Fe particle exposure (0 or 1 Gy, at either 300 or 1000 MeV/n) and brains were harvested at early (24h), intermediate (7d), and/or long time points (2-3mo) post-irradiation. (56)Fe particle exposure resulted in a robust increase in 53BP1+ foci at both the intermediate and long time points post-irradiation, suggesting long-term genomic instability in the brain. However, (56)Fe particle exposure only produced a transient decrease in immature neuron number at the intermediate time point, with no significant decrease at the long time point post-irradiation. (56)Fe particle exposure similarly produced a transient decrease in dividing progenitors, with fewer progenitors labeled at the early time point but equal number labeled at the intermediate time point, suggesting a recovery of neurogenesis. Notably, (56)Fe particle exposure did not change the total number of nestin-expressing neural stem cells. These results highlight that despite the persistence of an index of genomic instability, (56)Fe particle-induced deficits in adult hippocampal neurogenesis may be transient. These

  16. 56Fe Particle Exposure Results in a Long-Lasting Increase in a Cellular Index of Genomic Instability and Transiently Suppresses Adult Hippocampal Neurogenesis in Vivo

    PubMed Central

    DeCarolis, Nathan A.; Rivera, Phillip D.; Ahn, Francisca; Amaral, Wellington Z.; LeBlanc, Junie A.; Malhotra, Shveta; Shih, Hung-Ying; Petrik, David; Melvin, Neal; Chen, Benjamin P.C.; Eisch, Amelia J.

    2014-01-01

    The high-LET HZE particles from galactic cosmic radiation pose tremendous health risks to astronauts, as they may incur sub-threshold brain injury or maladaptations that may lead to cognitive impairment. The health effects of HZE particles are difficult to predict and unfeasible to prevent. This underscores the importance of estimating radiation risks to the central nervous system as a whole as well as to specific brain regions like the hippocampus, which is central to learning and memory. Given that neurogenesis in the hippocampus has been linked to learning and memory, we investigated the response and recovery of neurogenesis and neural stem cells in the adult mouse hippocampal dentate gyrus after HZE particle exposure using two nestin transgenic reporter mouse lines to label and track radial glia stem cells (Nestin-GFP and Nestin-CreERT2/R26R:YFP mice, respectively). Mice were subjected to 56Fe particle exposure (0 or 1 Gy, at either 300 or 1000 MeV/n) and brains were harvested at early (24h), intermediate (7d), and/or long time points (2–3mo) post-irradiation. 56Fe particle exposure resulted in a robust increase in 53BP1+ foci at both the intermediate and long time points post-irradiation, suggesting long-term genomic instability in the brain. However, 56Fe particle exposure only produced a transient decrease in immature neuron number at the intermediate time point, with no significant decrease at the long time point post-irradiation. 56Fe particle exposure similarly produced a transient decrease in dividing progenitors, with fewer progenitors labeled at the early time point but equal number labeled at the intermediate time point, suggesting a recovery of neurogenesis. Notably, 56Fe particle exposure did not change the total number of nestin-expressing neural stem cells. These results highlight that despite the persistence of an index of genomic instability, 56Fe particle-induced deficits in adult hippocampal neurogenesis may be transient. These data support

  17. Protective effect of quercetin on acute lung injury in rats with sepsis and its influence on ICAM-1 and MIP-2 expression.

    PubMed

    Meng, L; Lv, Z; Yu, Z Z; Xu, D; Yan, X

    2016-07-29

    This study aimed to explore the protective effect of quercetin on acute lung injury (ALI) in rats with sepsis and the related mechanism. Rats were administered different doses of quercetin intraperitoneally, and blood samples and lung tissue were collected at 24 h after treatment. Arterial blood gases, lung water content, protein content, and cell counts in bronchoalveolar lavage fluid (BALF) were measured. Morphological changes in lung tissue pathology were observed under a light microscope. Serum intercellular adhesion molecule (ICAM)-1 and macrophage inflammatory protein 2 (MIP-2) levels were detected and ICAM-1 and MIP-2 mRNA expression in lung tissue was determined. Compared with that in the control model group, arterial blood gases, lung water content, protein content, and cell counts in BALF improved in the high- and low-dose quercetin groups (P < 0.05), with maximal improvement observed for the high-dose quercetin (P < 0.05). Lesions on the lungs improved in the high- and low-dose quercetin groups than those in the control model group, and the high-dose quercetin group showed better improvement than the low-dose group (P < 0.05). Compared with that in the sham-operated group, both serum and lung tissue ICAM-1 and MIP-2 expression increased significantly in the model group (P < 0.05). The quercetin groups presented lower ICAM-1 and MIP-2 expression than the control model group, with the lowest expression observed in the high-dose group (P < 0.05). Quercetin may protect against ALI in rats with sepsis by inhibiting ICAM-1 and MIP-2 expression.

  18. Quercetin induces cell cycle arrest and apoptosis in CD133+ cancer stem cells of human colorectal HT29 cancer cell line and enhances anticancer effects of doxorubicin

    PubMed Central

    Atashpour, Shekoufeh; Fouladdel, Shamileh; Movahhed, Tahereh Komeili; Barzegar, Elmira; Ghahremani, Mohammad Hossein; Ostad, Seyed Nasser; Azizi, Ebrahim

    2015-01-01

    Objective(s): The colorectal cancer stem cells (CSCs) with the CD133+ phenotype are a rare fraction of cancer cells with the ability of self-renewal, unlimited proliferation and resistance to treatment. Quercetin has anticancer effects with the advantage of exhibiting low side effects. Therefore, we evaluated the anticancer effects of quercetin and doxorubicin (Dox) in HT29 cancer cells and its isolated CD133+ CSCs. Materials and Methods: The CSCs from HT29 cells were isolated using CD133 antibody conjugated to magnetic beads by MACS. Anticancer effects of quercetin and Dox alone and in combination on HT29 cells and CSCs were evaluated using MTT cytotoxicity assay and flow cytometry analysis of cell cycle distribution and apoptosis induction. Results: The CD133+ CSCs comprised about 10% of HT29 cells. Quercetin and Dox alone and in combination inhibited cell proliferation and induced apoptosis in HT29 cells and to a lesser extent in CSCs. Quercetin enhanced cytotoxicity and apoptosis induction of Dox at low concentration in both cell populations. Quercetin and Dox and their combination induced G2/M arrest in the HT29 cells and to a lesser extent in CSCs. Conclusion: The CSCs were a minor population with a significantly high level of drug resistance within the HT29 cancer cells. Quercetin alone exhibited significant cytotoxic effects on HT29 cells and also increased cytoxicity of Dox in combination therapy. Altogether, our data showed that adding quercetin to Dox chemotherapy is an effective strategy for treatment of both CSCs and bulk tumor cells. PMID:26351552

  19. Elevated Ca2+ transients and increased myofibrillar power generation cause cardiac hypercontractility in a model of Noonan syndrome with multiple lentigines.

    PubMed

    Clay, Sarah A; Domeier, Timothy L; Hanft, Laurin M; McDonald, Kerry S; Krenz, Maike

    2015-05-01

    Noonan syndrome with multiple lentigines (NSML) is primarily caused by mutations in the nonreceptor protein tyrosine phosphatase SHP2 and associated with congenital heart disease in the form of pulmonary valve stenosis and hypertrophic cardiomyopathy (HCM). Our goal was to elucidate the cellular mechanisms underlying the development of HCM caused by the Q510E mutation in SHP2. NSML patients carrying this mutation suffer from a particularly severe form of HCM. Drawing parallels to other, more common forms of HCM, we hypothesized that altered Ca(2+) homeostasis and/or sarcomeric mechanical properties play key roles in the pathomechanism. We used transgenic mice with cardiomyocyte-specific expression of Q510E-SHP2 starting before birth. Mice develop neonatal onset HCM with increased ejection fraction and fractional shortening at 4-6 wk of age. To assess Ca(2+) handling, isolated cardiomyocytes were loaded with fluo-4. Q510E-SHP2 expression increased Ca(2+) transient amplitudes during excitation-contraction coupling and increased sarcoplasmic reticulum Ca(2+) content concurrent with increased expression of sarco(endo)plasmic reticulum Ca(2+)-ATPase. In skinned cardiomyocyte preparations from Q510E-SHP2 mice, force-velocity relationships and power-load curves were shifted upward. The peak power-generating capacity was increased approximately twofold. Transmission electron microscopy revealed that the relative intracellular area occupied by sarcomeres was increased in Q510E-SHP2 cardiomyocytes. Triton X-100-based myofiber purification showed that Q510E-SHP2 increased the amount of sarcomeric proteins assembled into myofibers. In summary, Q510E-SHP2 expression leads to enhanced contractile performance early in disease progression by augmenting intracellular Ca(2+) cycling and increasing the number of power-generating sarcomeres. This gives important new insights into the cellular pathomechanisms of Q510E-SHP2-associated HCM.

  20. The supplement-drug interaction of quercetin with tamsulosin on vasorelaxation.

    PubMed

    Vrolijk, Misha F; Haenen, Guido R M M; Opperhuizen, Antoon; Jansen, Eugène H J M; Schiffers, Paul M; Bast, Aalt

    2015-01-01

    The food supplement quercetin is used as self-medication for prostate disorders and is known to induce vasorelaxation. The drug tamsulosin is used in the treatment of benign prostatic hyperplasia. A major side effect of tamsulosin is orthostatic hypotension, mediated by vasorelaxation resulting from α1-adrenoceptor blockade. The overlapping profile prompted us to investigate the pharmacodynamic interaction of quercetin with tamsulosin. Since quercetin is extensively metabolized in the intestines and the liver, the metabolites quercetin-3-glucuronide and 4'O-methyl-quercetin were also examined. Vasorelaxation induced by the compounds was tested in rat mesenteric arteries (average diameter: 360±μm) constricted by the α1-adrenoceptor agonist phenylephrine. Tamsulosin (0.1nM) decreased phenylephrine sensitivity 17-fold (n=10). Quercetin (5, 10 and 20µM) also caused a decrease (2-, 4- and 6-fold respectively) of phenylephrine sensitivity, while 10µM of quercetin-3-glucuronide and 4'O-methyl-quercetin decreased this sensitivity (1.5- and 2-fold) only slightly (n=6). The combination of tamsulosin with quercetin or quercetin metabolites proved to be far more potent than the compounds in isolation. The combination of quercetin, quercetin-3-glucuronide or 4'O-methyl-quercetin with tamsulosin decreased the phenylephrine sensitivity approximately 200-, 35- and 150-fold (n=6). The strong pharmacodynamic interaction between the food supplement quercetin and tamsulosin underlines the potential of the impact of supplement-drug interactions that warrant more research.

  1. Pharmacokinetic comparison between quercetin and quercetin 3-O-β-glucuronide in rats by UHPLC-MS/MS

    PubMed Central

    Yang, Le-Le; Xiao, Na; Li, Xiao-Wei; Fan, Yong; Alolga, Raphael N.; Sun, Xiao-Yue; Wang, Shi-Lei; Li, Ping; Qi, Lian-Wen

    2016-01-01

    Quercetin is a natural flavonoid widely distributed in human diet and functional foods. Quercetin 3-O-β-glucuronide (Q3G) is present in wine and some medicinal plants. Quercetin and Q3G may be metabolized from each other in vivo. While quercetin has been the subject of many studies, the pharmacokinetic profiles of quercetin and Q3G (in animals) have not yet been compared. Herein, we prepared a column-based method for rapid isolation of Q3G from Nelumbo nucifera. Then, we developed an UHPLC-MS/MS method to compare the pharmacokinetics of quercetin and Q3G. Our results showed that the plasma concentration-time curves of quercetin and Q3G show two maxima (Tmax1 ≈ 0.75 h, Tmax2 ≈ 5 h). After oral administration of 100 mg/kg quercetin or 100 mg/kg Q3G in rats, predominantly Q3G was detected in plasma with AUC at 39529.2 ± 6108.2 mg·h·L−1 or 24625.1 ± 1563.8 mg·h·L−1, 18-fold higher than quercetin with AUC at 1583.9 ± 583.3 mg·h·L−1 or 1394.6 ± 868.1 mg·h·L−1, respectively. After intravenous injection of 10 mg/kg in rats, Q3G showed extensive tissue uptake in kidney (409.2 ± 118.4 ng/g), liver (166.1 ± 52.9 ng/g), heart (97.7 ± 22.6 ng/g), and brain (5.8 ± 1.2 ng/g). In conclusion, we have shown that Q3G is a major active component in plasma and tissue for oral administration of quercetin or Q3G. PMID:27775094

  2. Evidence that prolonged histamine suffusions produce transient increases in vascular permeability subsequent to the formation of venular macromolecular leakage sites. Proof of the Majno-Palade hypothesis.

    PubMed Central

    Horan, K. L.; Adamski, S. W.; Ayele, W.; Langone, J. J.; Grega, G. J.

    1986-01-01

    ), the [FITC-D]s and the number of vascular leakage sites were markedly increased. However, when the tracer was injected intravenously 30 minutes after the start of the 60-minute histamine suffusion, there were only minimal increases in [FITC-D]s and the formation of venular leakage sites. These findings suggest that prolonged suffusions of histamine produce transient increases in macromolecular efflux which are dependent on the formation of discrete venular macromolecular leakage sites.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:2424313

  3. Transient response of the Hadley Centre coupled ocean-atmosphere model to increasing carbon dioxide. Part 3: Analysis of global-mean response using simple models

    SciTech Connect

    Murphy, J.M.

    1995-03-01

    The roles of surface, atmospheric, and oceanic feedbacks in controlling the global-mean transient response of a coupled ocean-atmosphere general circulation model (AOGCM) to increasing carbon dioxide are investigated. The analysis employs a four-box energy balance model (EBM) and an oceanic box-diffusion model (BDM) both tuned to the simulated general circulation model response. The land-sea contrast in the surface warming is explained almost entirely by the shortwave radiative feedbacks associated with changes in cloud and surface albedo. The oceanic thermal inertia delays the response; however, the initial delay is enhanced by increases in Anarctic sea-ice cover, which substantially reduce the effective climate sensitivity of the model in the first half of the 75-year experiment. When driven by the observed anthropogenic greenhouse forcing from the pre-industrial period to present day, the energy balance model overestimates the warming observed over land. However, inclusion of the direct forcing due to anthropogenic tropospheric sulphate aerosol eliminates the land/sea contrast in the response at 1990, leaving the simulated warming over land slightly below the observed value, although the rapid warming observed during the 1980s is well reproduced. The vertical penetration of the oceanic response is small below 1000 m. Within the top 1000 m the effective diffusivities are substantially enhanced by reduced convection and thermohaline overturning, driven by increased precipitation minus evaporation at high latitudes. These changes in ocean heat transport become significant after year 30, whereupon the effective oceanic heat capacity increases substantially, although this increase is partially offset by the effect of changes in the sea-ice margin.

  4. Quercetin and quercetin 3-O-glycosides from Bauhinia longifolia (Bong.) Steud. show anti-Mayaro virus activity

    PubMed Central

    2014-01-01

    Background The arthropod-borne Mayaro virus (MAYV) causes ‘Mayaro fever’, a disease of medical significance, primarily affecting individuals in permanent contact with forested areas in tropical South America. Recently, MAYV has attracted attention due to its likely urbanization. Currently, there are no licensed drugs against most mosquito-transmitted viruses. Here, we investigated the in vitro anti-MAYV activity of the flavonoids quercetin and its derivatives from the Brazilian shrub Bauhinia longifolia (Bong.) Steud. Methods Flavonoids were purified by chromatographic fractionation from leaf extracts of B. longifolia and chemically identified as quercetin and quercetin glycosides using spectroscopic techniques. Cytotoxicity of purified flavonoids and of EtOAc- and n-BuOH-containing flavonoid mixtures was measured by the dye-uptake assay while their antiviral activity was evaluated by a virus yield inhibition assay. Results The following flavonoids were purified from B. longifolia leaves: non-glycosylated quercetin and its glycosides guaijaverin, quercitrin, isoquercitrin, and hyperin. EtOAc and n-BuOH fractions containing these flavonoids demonstrated the highest antiviral activity of all tested substances, while quercetin had the highest antiviral activity amongst purified flavonoids. Quercetin, EtOAc, or n-BuOH fractions inhibited MAYV production by more than 90% at 25 μg/mL, displaying a stronger antiviral effect than the licensed antiviral ribavirin. A mixture of the isomers isoquercitrin and hyperin had a modest antiviral effect (IC90 = 104.9), while guaijaverin and quercitrin did not show significant antiviral activity. Conclusions B. longifolia is a good source of flavonoids with anti-Mayaro virus activity. This is the first report of the activity of quercetin and its derivatives against an alphavirus. PMID:24678592

  5. Inhibitory effect of quercetin on periodontal pathogens in vitro.

    PubMed

    Geoghegan, F; Wong, R W K; Rabie, A B M

    2010-06-01

    Actinobacillus actinomycetemcomitans (Aa) and Porphyromonas gingivalis (Pg) are bacteria strongly associated with early onset, progressive and refractory periodontal disease and associated alveolar bone loss. Quercetin is a flavonoid found in many foods including apples, onions and tea. The aim of this study was to evaluate the effect of quercetin on in vitro growth of periodontal pathogens Aa and Pg. For comparison, quercetin's effect on several oral microbes was also evaluated. Different concentrations of quercetin solution were added to calibrated suspensions of Aa and Pg. All suspensions were incubated for 1, 3, 6, and 24 h in an anaerobic chamber at 37 degrees C. At each time point, selected dilutions from each culture broth were plated on blood agar plates. Colonies appearing on blood agar plates were visually counted on 3 days for Aa and 5 days for Pg. Minimum inhibitory concentrations of both periodontal pathogens were also determined. Both periodontal bacteria showed a significant decrease (p < 0.05) in viable counts after 1 h. No colony forming units of Pg could be observed after 24 h. The results suggest that quercetin possesses significant antimicrobial properties on periodontal pathogens in vitro. PMID:19957242

  6. Site-specific anticancer effects of dietary flavonoid quercetin.

    PubMed

    Sak, Katrin

    2014-01-01

    Food-derived flavonoid quercetin, widely distributed in onions, apples, and tea, is able to inhibit growth of various cancer cells indicating that this compound can be considered as a good candidate for anticancer therapy. Although the exact mechanism of this action is not thoroughly understood, behaving as antioxidant and/or prooxidant as well as modulating different intracellular signalling cascades may all play a certain role. Such inhibitory activity of quercetin has been shown to depend first of all on cell lines and cancer types; however, no comprehensive site-specific analysis of this effect has been published. In this review article, cytotoxicity constants of quercetin measured in various human malignant cell lines of different origin were compiled from literature and a clear cancer selective action was demonstrated. The most sensitive malignant sites for quercetin revealed to be cancers of blood, brain, lung, uterine, and salivary gland as well as melanoma whereas cytotoxic activity was higher in more aggressive cells compared to the slowly growing cells showing that the most harmful cells for the organism are probably targeted. More research is needed to overcome the issues of poor water solubility and relatively low bioavailability of quercetin as the major obstacles limiting its clinical use. PMID:24377461

  7. Relationship between exercise-induced heart rate increase and the formation of microbubbles and high-intensity transient signals in mechanical heart valve implanted patients

    PubMed Central

    Sünbül, Ayşegül; Tanrıkulu, Nursen; Şengül, Cihan; Dağdeviren, Bahadır; Işık, Ömer

    2013-01-01

    Introduction The formation and collapse of vapor-filled bubbles near a mechanical heart valve is called cavitation. Microbubbles can be detected in vivo by doppler ultrasonography (USG) as HITS (high intensity transient signals) in cranial circulation. We investigated the relationship between exercise induced heart rate increase and HITS formation in cranial circulation. Material and methods Thirty-nine mechanical heart valve implanted (8 aortic valve replacement (AVR) + mitral valve replacement (MVR), 9 AVR, 22 MVR) patients aged 18-80 years old were included in our study. Microbubbles were counted in the left ventricular cavity via transthoracic echocardiography at rest per cardiac cycle. Afterwards transcranial Doppler USG was performed and HITS were counted in each patient's middle cerebral artery at 5 min duration. Subsequently an exercise test according to the Bruce protocol was performed. After achieving maximal heart rate, microbubbles in the left ventricle and HITS were counted again. Results Microbubbles in the left ventricle and transcranial HITS increased after exercise significantly compared to resting values (15.79 ±10.91 microbubbles/beat vs. 26.51 ±18.00 microbubbles/beat, p < 0.001; 6.13 ±8.07 HITS/5 min vs. 13.15 ±15.87 HITS/5 min, p = 0.001). There was a significant correlation between microbubbles and HITS counts after peak exercise (r = 0.55, p < 0.001). Conclusions In our study, we found that the microbubbles were increasing as the heart rate increased and more HITS were propelled to the cerebral circulation. As previously shown, HITS can alter cognitive functions. Therefore heart rate control is essential in mechanical heart valve patients to protect neurocognitive functions. PMID:25276153

  8. Folic acid deficiency increases delayed neuronal death, DNA damage, platelet endothelial cell adhesion molecule-1 immunoreactivity, and gliosis in the hippocampus after transient cerebral ischemia.

    PubMed

    Hwang, In Koo; Yoo, Ki-Yeon; Suh, Hong-Won; Kim, Young Sup; Kwon, Dae Young; Kwon, Young-Guen; Yoo, Jun-Hyun; Won, Moo-Ho

    2008-07-01

    Folic acid deficiency increases stroke risk. In the present study, we examined whether folic acid deficiency enhances neuronal damage and gliosis via oxidative stress in the gerbil hippocampus after transient forebrain ischemia. Animals were exposed to a folic acid-deficient diet (FAD) for 3 months and then subjected to occlusion of both common carotid arteries for 5 min. Exposure to an FAD increased plasma homocysteine levels by five- to eightfold compared with those of animals fed with a control diet (CD). In CD-treated animals, most neurons were dead in the hippocampal CA1 region 4 days after ischemia/reperfusion, whereas, in FAD-treated animals, this occurred 3 days after ischemia/reperfusion. Immunostaining for 8-hydroxy-2'-deoxyguanosine (8-OHdG) was performed to examine DNA damage in CA1 neurons in both groups after ischemia, and it was found that 8-OHdG immunoreactivity in both FAD and CD groups peaked at 12 hr after reperfusion, although the immunoreactivity in the FAD group was much greater than that in the CD group. Platelet endothelial cell adhesion molecule-1 (PECAM-1; a final mediator of neutrophil transendothelial migration) immunoreactivity in both groups increased with time after ischemia/reperfusion: Its immunoreactivity in the FAD group was much higher than that in the CD group 3 days after ischemia/reperfusion. In addition, reactive gliosis in the ischemic CA1 region increased with time after ischemia in both groups, but astrocytosis and microgliosis in the FAD group were more severe than in the CD group at all times after ischemia. Our results suggest that folic acid deficiency enhances neuronal damage induced by ischemia.

  9. Amperometric monitoring of quercetin permeation through skin membranes.

    PubMed

    Rembiesa, Jadwiga; Gari, Hala; Engblom, Johan; Ruzgas, Tautgirdas

    2015-12-30

    Transdermal delivery of quercetin (QR, 3,3',4',5,7-pentahydroxyflavone), a natural flavonoid with a considerable antioxidant capacity, is important for medical treatment of, e.g., skin disorders. QR permeability through skin is low, which, at the same time, makes the monitoring of percutaneous QR penetration difficult. The objective of this study was to assess an electrochemical method for monitoring QR penetration through skin membranes. An electrode was covered with the membrane, exposed to QR solution, and electrode current was measured. The registered current was due to electro-oxidation of QR penetrating the membrane. Exploiting strict current-QR flux relationships diffusion coefficient, D, of QR in skin and dialysis membranes was calculated. The D values were strongly dependent on the theoretical model and parameters assumed in the processing of the amperometric data. The highest values of D were in the range of 1.6-6.1×10(-7)cm(2)/s. This was reached only for skin membranes pretreated with buffer-ethanol mixture for more than 24h. QR solutions containing penetration enhancers, ethanol and l-menthol, definitely increased D values. The results demonstrate that electrochemical setup gives a possibility to assess penetration characteristics as well as enables monitoring of penetration dynamics, which is more difficult by traditional methods using Franz cells.

  10. Quercetin Influence on Thermal Denaturation of Bovine Serum Albumin.

    PubMed

    Precupas, Aurica; Sandu, Romica; Popa, Vlad T

    2016-09-01

    The effect of quercetin (QUER) binding on bovine serum albumin (BSA) thermal denaturation was systematically investigated by means of differential scanning calorimetry (DSC). Additional information concerning thermodynamic and structural binding parameters was provided by isothermal titration calorimetry (ITC) and molecular docking. The most relevant effect of QUER is manifested in the modification of the two-step thermal fingerprint of protein denaturation. Higher QUER concentrations result in a single-step denaturation thermogram, ascribed to the interplay between specific and nonspecific binding and enhancement of the solvent unfolding action. Analysis of ITC data indicate sequential binding of two molecules of QUER occurring spontaneously at different binding sites of BSA involving hydrophobic, electrostatic and hydrogen binding forces. Identification of QUER binding sites was possible through corroboration of DSC runs in the presence of site markers and molecular docking. Modeling of ligand-protein interaction confirmed the experimental data. On one hand, a neutral form of QUER binds in a nonplanar conformation to Sudlow's site I, a large hydrophobic cavity of subdomain IIA of BSA and decreases its thermal stability. On the other hand, a second molecule of QUER, the anionic form, is bound in planar conformation to Sudlow's site II, situated in the subdomain IIIA of the folded protein, and increases the thermal stability of the corresponding structural domain of the protein. PMID:27505141

  11. Effects of vitamin D and quercetin, alone and in combination, on cardiorespiratory fitness and muscle function in physically active male adults

    PubMed Central

    Scholten, Shane D; Sergeev, Igor N; Song, Qingming; Birger, Chad B

    2015-01-01

    Introduction Vitamin D and the antioxidant quercetin, are promising agents for improving physical performance because of their possible beneficial effects on muscular strength and cardiorespiratory fitness. Purpose The purpose of this study was to determine the effects of increased intakes of vitamin D, quercetin, and their combination on antioxidant status, the steroid hormone regulators of muscle function, and measures of physical performance in apparently healthy male adults engaged in moderate-to-vigorous-intensity exercise training. Methods A total of 40 adult male participants were randomized to either 4,000 IU vitamin D/d, 1,000 mg/d quercetin, vitamin D plus quercetin, or placebo for 8 weeks. Measures of cardiorespiratory fitness and muscle function, blood markers for antioxidant and vitamin D status, and hormones 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and testosterone were measured pre- and postsupplementation. Results At enrollment, 88.6% of participants were vitamin D sufficient (serum 25-hydroxyvitamin D >50 nmol/L) and had normal serum testosterone levels. Supplementation with vitamin D significantly increased serum 25(OH)D concentration (by 87.3% in the vitamin D group, P<0.001) and was associated with an increasing trend of testosterone concentration. There were no changes in concentration of 1,25(OH)2D3 and markers of antioxidant status associated with vitamin D or quercetin supplementation. No improvements in physical performance measures associated with vitamin D and quercetin supplementation were found. Conclusion The findings obtained demonstrate that long-term vitamin D and quercetin supplementation, alone or in combination, does not improve physical performance in male adults with adequate vitamin D, testosterone, and antioxidant status. PMID:26244032

  12. Systemic exposure of Paracetamol (acetaminophen) was enhanced by quercetin and chrysin co-administration in Wistar rats and in vitro model: risk of liver toxicity.

    PubMed

    Pingili, Ravindra Babu; Pawar, A Krishnamanjari; Challa, Siva R

    2015-01-01

    Intestinal P-glycoprotein (P-gp) and drug-metabolizing enzymes (DMEs) play an important role in the first-pass-metabolism (FPM) and pharmacokinetics (PK) of majority of drugs. Paracetamol is primarily metabolized by conjugation reactions and a little amount (∼15%) undergoes cytochrome P450 (CYP2E1)-mediated oxidative metabolism produces a hepatotoxic metabolite, N-acetyl-p-benzoquinonimine (NAPQI). Quercetin and chrysin are naturally occurring flavonoids, reported as modulators of P-gp and DMEs. Therefore, the objective of this study was to evaluate the effects of quercetin and chrysin on the pharmacokinetics of paracetamol using rats and non-everted gut sacs in vitro. Paracetamol was given orally (100 mg/kg) to rats alone and in combination with quercetin (5, 10 and 20 mg/kg) and chrysin (50, 100 and 200 mg/kg) once daily for 21 consecutive days. Blood samples were collected on the 1st day in single dose pharmacokinetic study (SDS) and on the 21st day in multiple pharmacokinetic studies (MDS). The plasma concentrations of paracetamol were determined by HPLC and PK parameters were calculated by using Kinetica (Version 5.1). The maximum plasma concentration (Cmax) and area under the curve (AUC0-12) of paracetamol was significantly increased by quercetin and chrysin co-administration in SDS and MDS. In non-everted rat gut sac method, the absorption of paracetamol was increased by presence of P-gp inhibitors (verapamil, quinidine and ketoconazole), quercetin and chrysin (50 μg/mL). Our findings suggested that the quercetin and chrysin might be inhibited the P-gp and metabolism of paracetamol; thereby increased the systemic exposure of paracetamol. Further studies are needed to evaluate whether the quercetin or chrysin are involved in the formation of NAPQI by CYP2E1 or not on isolated rat hepatocytes or using cell lines.

  13. Spinal transient receptor potential ankyrin 1 channel induces mechanical hypersensitivity, increases cutaneous blood flow, and mediates the pronociceptive action of dynorphin A.

    PubMed

    Wei, H; Saarnilehto, M; Falck, L; Viisanen, H; Lasierra, M; Koivisto, A; Pertovaara, A

    2013-06-01

    We characterized pain behavior and cutaneous blood flow response induced by activation of the spinal transient receptor potential ankyrin 1 (TRPA1) channel using intrathecal drug administrations in the rat. Additionally, we assessed whether the pronociceptive actions induced by intrathecally administered dynorphin A, cholecystokinin or prostaglandin F(2α) are mediated by the spinal TRPA1 channel. Cinnamaldehyde, a TRPA1 agonist, produced a dose-related (3-10 μg) cutaneous blood flow increase and mechanical hypersensitivity effect. These effects at the currently used doses were of short duration and attenuated, although not completely, by pretreatment with A-967079, a TRPA1 antagonist. The cinnamaldehyde-induced hypersensitivity was also reduced by pretreatment with minocycline (an inhibitor of microglial activation), but not by carbenoxolone (a gap junction decoupler). In vitro study, however, indicated that minocycline only poorly blocks the TRPA1 channel. The mechanical hypersensitivity effect induced by dynorphin A, but not that by cholecystokinin or prostaglandin F(2α), was attenuated by a TRPA1 antagonist Chembridge-5861528 as well as A-967079. The cinnamaldehyde-induced cutaneous blood flow increase was not suppressed by MK-801, an NMDA receptor antagonist, or bicuculline, a GABA(A) receptor antagonist. The results indicate that spinal TRPA1 channels promote mechanical pain hypersensitivity and due to antidromic activation of nociceptive nerve fibers increase cutaneous blood flow. The attenuation of the cinnamaldehyde-induced hypersensitivity effect by minocycline may be explained by action other than block of the TRPA1 channel. Moreover, the spinal TRPA1 channel is involved in mediating the pronociceptive action of dynorphin A, but not that of the spinal cholecystokinin or prostaglandin F(2α).

  14. In Vivo Human Left-to-Right Ventricular Differences in Rate Adaptation Transiently Increase Pro-Arrhythmic Risk following Rate Acceleration

    PubMed Central

    Bueno-Orovio, Alfonso; Hanson, Ben M.; Gill, Jaswinder S.; Taggart, Peter; Rodriguez, Blanca

    2012-01-01

    Left-to-right ventricular (LV/RV) differences in repolarization have been implicated in lethal arrhythmias in animal models. Our goal is to quantify LV/RV differences in action potential duration (APD) and APD rate adaptation and their contribution to arrhythmogenic substrates in the in vivo human heart using combined in vivo and in silico studies. Electrograms were acquired from 10 LV and 10 RV endocardial sites in 15 patients with normal ventricles. APD and APD adaptation were measured during an increase in heart rate. Analysis of in vivo electrograms revealed longer APD in LV than RV (207.8±21.5 vs 196.7±20.1 ms; P<0.05), and slower APD adaptation in LV than RV (time constant τs = 47.0±14.3 vs 35.6±6.5 s; P<0.05). Following rate acceleration, LV/RV APD dispersion experienced an increase of up to 91% in 12 patients, showing a strong correlation (r2 = 0.90) with both initial dispersion and LV/RV difference in slow adaptation. Pro-arrhythmic implications of measured LV/RV functional differences were studied using in silico simulations. Results show that LV/RV APD and APD adaptation heterogeneities promote unidirectional block following rate acceleration, albeit being insufficient for establishment of reentry in normal hearts. However, in the presence of an ischemic region at the LV/RV junction, LV/RV heterogeneity in APD and APD rate adaptation promotes reentrant activity and its degeneration into fibrillatory activity. Our results suggest that LV/RV heterogeneities in APD adaptation cause a transient increase in APD dispersion in the human ventricles following rate acceleration, which promotes unidirectional block and wave-break at the LV/RV junction, and may potentiate the arrhythmogenic substrate, particularly in patients with ischemic heart disease. PMID:23284948

  15. Increases in reactive oxygen species enhance vascular endothelial cell migration through a mechanism dependent on the transient receptor potential melastatin 4 ion channel.

    PubMed

    Sarmiento, Daniela; Montorfano, Ignacio; Cerda, Oscar; Cáceres, Mónica; Becerra, Alvaro; Cabello-Verrugio, Claudio; Elorza, Alvaro A; Riedel, Claudia; Tapia, Pablo; Velásquez, Luis A; Varela, Diego; Simon, Felipe

    2015-03-01

    A hallmark of severe inflammation is reactive oxygen species (ROS) overproduction induced by increased inflammatory mediators secretion. During systemic inflammation, inflammation mediators circulating in the bloodstream interact with endothelial cells (ECs) raising intracellular oxidative stress at the endothelial monolayer. Oxidative stress mediates several pathological functions, including an exacerbated EC migration. Because cell migration critically depends on calcium channel-mediated Ca(2+) influx, the molecular identification of the calcium channel involved in oxidative stress-modulated EC migration has been the subject of intense investigation. The transient receptor potential melastatin 4 (TRPM4) protein is a ROS-modulated non-selective cationic channel that performs several cell functions, including regulating intracellular Ca(2+) overload and Ca(2+) oscillation. This channel is expressed in multiple tissues, including ECs, and contributes to the migration of certain immune cells. However, whether the TRPM4 ion channel participates in oxidative stress-mediated EC migration is not known. Herein, we investigate whether oxidative stress initiates or enhances EC migration and study the role played by the ROS-modulated TRPM4 ion channel in oxidative stress-mediated EC migration. We demonstrate that oxidative stress enhances, but does not initiate, EC migration in a dose-dependent manner. Notably, we demonstrate that the TRPM4 ion channel is critical in promoting H2O2-enhanced EC migration. These results show that TRPM4 is a novel pharmacological target for the possible treatment of severe inflammation and other oxidative stress-mediated inflammatory diseases.

  16. [A case of probable catastrophic antiphospholipid syndrome with multi-organ failure presenting as a transient increase of antiphospholipid antibody levels].

    PubMed

    Sato, Rubuna; Sato, Hiroshi; Nishiwaki, Atsuma; Yokoe, Isamu; Tsuruta, Shinji; Haraoka, Hitomi

    2014-01-01

    A 44-year-old woman was admitted to our hospital with shock, massive pneumonia and respiratory failure, liver and renal dysfunction, and cerebral infarction. Based on these symptoms, we suspected the presence of disseminated intravascular coagulation and multiple organ dysfunctions due to massive pneumonia or catastrophic antiphospholipid syndrome (CAPS). Therefore, the patient was placed on a respirator and was administered ciprofloxacin, doripenem hydrate, thrombomodulin, antithrombin III, and methylprednisolone pulse therapy. Because the patient's antiphospholipid antibody titer was low on the day of admission (day 1), we did not include CAPS in the differential diagnosis and discontinued prednisolone treatment on day 6. However, the anticardiolipin immunoglobulin M antibody titer was found to be elevated on day 7; in addition, a transient increase in the anticardiolipin anti-β2 glycoprotein antibody titer was noted on re-examination. Moreover, on day 8, the thrombopenia and alveolar hemorrhage suddenly exacerbated. We finally diagnosed the patient with CAPS, and therefore resumed methylprednisolone therapy. Subsequently, the inflammation, respiratory failure, and thrombopenia rapidly improved, and the patient was extubated on day 12.

  17. Increases in reactive oxygen species enhance vascular endothelial cell migration through a mechanism dependent on the transient receptor potential melastatin 4 ion channel.

    PubMed

    Sarmiento, Daniela; Montorfano, Ignacio; Cerda, Oscar; Cáceres, Mónica; Becerra, Alvaro; Cabello-Verrugio, Claudio; Elorza, Alvaro A; Riedel, Claudia; Tapia, Pablo; Velásquez, Luis A; Varela, Diego; Simon, Felipe

    2015-03-01

    A hallmark of severe inflammation is reactive oxygen species (ROS) overproduction induced by increased inflammatory mediators secretion. During systemic inflammation, inflammation mediators circulating in the bloodstream interact with endothelial cells (ECs) raising intracellular oxidative stress at the endothelial monolayer. Oxidative stress mediates several pathological functions, including an exacerbated EC migration. Because cell migration critically depends on calcium channel-mediated Ca(2+) influx, the molecular identification of the calcium channel involved in oxidative stress-modulated EC migration has been the subject of intense investigation. The transient receptor potential melastatin 4 (TRPM4) protein is a ROS-modulated non-selective cationic channel that performs several cell functions, including regulating intracellular Ca(2+) overload and Ca(2+) oscillation. This channel is expressed in multiple tissues, including ECs, and contributes to the migration of certain immune cells. However, whether the TRPM4 ion channel participates in oxidative stress-mediated EC migration is not known. Herein, we investigate whether oxidative stress initiates or enhances EC migration and study the role played by the ROS-modulated TRPM4 ion channel in oxidative stress-mediated EC migration. We demonstrate that oxidative stress enhances, but does not initiate, EC migration in a dose-dependent manner. Notably, we demonstrate that the TRPM4 ion channel is critical in promoting H2O2-enhanced EC migration. These results show that TRPM4 is a novel pharmacological target for the possible treatment of severe inflammation and other oxidative stress-mediated inflammatory diseases. PMID:24518820

  18. Liquid chromatography-tandem mass spectroscopy assay for quercetin and conjugated quercetin metabolites in human plasma and urine.

    PubMed

    Wang, Liang; Morris, Marilyn E

    2005-07-25

    A sensitive and specific method was developed and validated for the quantitation of quercetin in human plasma and urine. The application of liquid chromatography-tandem mass spectrometry (LC/MS/MS) with a TurboIonspray (TIS) interface in negative mode under multiple reactions monitoring was investigated. Chromatographic separation was achieved on a C12 column using a mobile phase of acetonitrile/water with 0.2% formic acid (pH 2.4) (40/60, v/v). The detection limit was 100 pg/ml and the lower limit of quantification was 500 pg/ml for plasma samples; the detection limit was 500 pg/ml and the lower limit of quantification was 1 ng/ml for urine samples. The calibration curve was linear from 1 to 800 ng/ml for plasma samples and was linear from 1 to 200 and 50 to 2000 ng/ml for urine samples. All the intra- and inter-day coefficients of variation were less than 11% and intra- and inter-day accuracies were within +/-15% of the known concentrations. This represents a LC/MS/MS assay with the sensitivity and specificity necessary to determine quercetin in human plasma and urine. This assay was used to determine both parent quercetin and the quercetin after enzymatic hydrolysis with beta-glucuronidase/sulfatase in human plasma and urine samples following the ingestion of quercetin 500 mg capsules.

  19. [Hypoglycemic and hypolipidemic effects of quercetin and its glycosides].

    PubMed

    Yan, Shu-xia; Li, Xian; Sun, Chong-de; Chen, Kun-song

    2015-12-01

    Quercetin and its glycosides are important flavonols in traditional herbal drugs and plant-derived food, and they have diverse hiological activities such as antioxidant, anticarcinogenic, anti-inflammatory, hypoglycemic and hypolipidemic activities. Numerous studies have demonstrated that quercetin and its glycosides were effective in the prevention and treatment of non-infectious chronic disease such as diabetes, obesity, and hyperlipidemia. They can regulate glucose and lipid metaholism through different mechanisms. They can decrease blood glucose via protecting pancreatic/p cells or/and improving insulin sensitivity. Also, they have lipid-lowering effects, which may be the result of regulation of lipid catabolism or/and anabolism. Their distributions, as well as the hypoglycemic and hypolipidemic effects are reviewed in this paper. In addition, further bioactivities as well as their dose-activity relationship, structure-activity relationship, bioavailability, and future clinical application of quercetin and its glycosides are discussed and proposed. PMID:27141664

  20. Quercetin as natural stabilizing agent for bio-polymer

    SciTech Connect

    Morici, Elisabetta; Arrigo, Rossella; Dintcheva, Nadka Tzankova

    2014-05-15

    The introduction of antioxidants in polymers is the main way to prevent or delay the degradation process. In particular natural antioxidants receive attention in the food industry also because of their presumed safety. In this work bio-polymers, i.e. a commercial starch-based polymer (Mater-Bi®) and a bio-polyester (PLA), and a bio-polyether (PEO) were additivated with quercetin, a natural flavonoid antioxidants, in order to formulate bio-based films for ecosustainable packaging and outdoor applications. The photo-oxidation behavior of unstabilized and quercetin stabilized films was analyzed and compared with the behavior of films additivated with a commercial synthetic light stabilizer. The quercetin is able to slow down the photo-degradation rate of all bio-polymeric films investigated in similar way to the synthetic stabilizer.

  1. Quercetin as natural stabilizing agent for bio-polymer

    NASA Astrophysics Data System (ADS)

    Morici, Elisabetta; Arrigo, Rossella; Dintcheva, Nadka Tzankova

    2014-05-01

    The introduction of antioxidants in polymers is the main way to prevent or delay the degradation process. In particular natural antioxidants receive attention in the food industry also because of their presumed safety. In this work bio-polymers, i.e. a commercial starch-based polymer (Mater-Bi®) and a bio-polyester (PLA), and a bio-polyether (PEO) were additivated with quercetin, a natural flavonoid antioxidants, in order to formulate bio-based films for ecosustainable packaging and outdoor applications. The photo-oxidation behavior of unstabilized and quercetin stabilized films was analyzed and compared with the behavior of films additivated with a commercial synthetic light stabilizer. The quercetin is able to slow down the photo-degradation rate of all bio-polymeric films investigated in similar way to the synthetic stabilizer.

  2. Pharmacokinetics of quercetin-loaded nanodroplets with ultrasound activation and their use for bioimaging

    PubMed Central

    Chang, Li-Wen; Hou, Mei-Ling; Hung, Shuo-Hui; Lin, Lie-Chwen; Tsai, Tung-Hu

    2015-01-01

    Bubble formulations have both diagnostic and therapeutic applications. However, research on nanobubbles/nanodroplets remains in the initial stages. In this study, a nanodroplet formulation was prepared and loaded with a novel class of chemotherapeutic drug, ie, quercetin, to observe its pharmacokinetic properties and ultrasonic bioimaging of specific sites, namely the abdominal vein and bladder. Four parallel groups were designed to investigate the effects of ultrasound and nanodroplets on the pharmacokinetics of quercetin. These groups were quercetin alone, quercetin triggered with ultrasound, quercetin-encapsulated in nanodroplets, and quercetin encapsulated in nanodroplets triggered with ultrasound. Spherical vesicles with a mean diameter of 280 nm were formed, and quercetin was completely encapsulated within. In vivo ultrasonic imaging confirmed that the nanodroplets could be treated by ultrasound. The results indicate that the initial 5-minute serum concentration, area under the concentration–time curve, elimination half-life, and clearance of quercetin were significantly enhanced by nanodroplets with or without ultrasound. PMID:25945049

  3. Femtomole level photoelectrochemical aptasensing for mercury ions using quercetin-copper(II) complex as the DNA intercalator.

    PubMed

    Li, Hongbo; Xue, Yan; Wang, Wei

    2014-04-15

    An ultrasensitive and selective photoelectrochemical (PEC) aptasensor for mercury ions was first fabricated based on perylene-3, 4, 9, 10-tetracarboxylic acid/graphene oxide (PTCA/GO) heterojunction using quercetin-copper(II) complex intercalated into the poly(dT)-poly(dA) duplexes. Both the PTCA/GO heterojunction and the quercetin-copper(II) complex are in favor of the sensitivity for the fabricated PEC aptasensor due to band alignment and strong reduction capability, respectively. And they efficiently promote the separation of photoexcited carriers and enhance the photocurrent. The formation of thymine-Hg(2+)-thymine coordination chemistry resulted in the dehybridization of poly(dT)-poly(dA) duplexes and then the intercalator quercetin-copper(II) complex broke away from the surface of the PEC aptasensor. As the concentration of mercury ions increased, the photocurrent gradually decreased. The electrode response for mercury ions detection was in the linear range from 0.01 pmol L(-1) to 1.00 pmol L(-1) with the detection limit of 3.33 fmol L(-1). The label-free PEC aptasensor has excellent performances with ultrasensitivity and good selectivity besides the advantage of economic and facile fabrication. The strategy of quercetin-copper(II) complex as a novel DNA intercalator paves a new way to improve the performances for PEC sensors. PMID:24291750

  4. Iron-Mediated Lysosomal Membrane Permeabilization in Ethanol-Induced Hepatic Oxidative Damage and Apoptosis: Protective Effects of Quercetin

    PubMed Central

    Li, Yanyan; Chen, Man; Xu, Yanyan; Yu, Xiao; Xiong, Ting; Du, Min; Sun, Jian; Liu, Liegang; Tang, Yuhan; Yao, Ping

    2016-01-01

    Iron, in its free ferrous states, can catalyze Fenton reaction to produce OH∙, which is recognized as a crucial role in the pathogenesis of alcoholic liver diseases (ALD). As a result of continuous decomposition of iron-containing compounds, lysosomes contain a pool of redox-active iron. To investigate the important role of intralysosomal iron in alcoholic liver injury and the potential protection of quercetin, male C57BL/6J mice fed by Lieber De Carli diets containing ethanol (30% of total calories) were cotreated by quercetin or deferoxamine (DFO) for 15 weeks and ethanol-incubated mice primary hepatocytes were pretreated with FeCl3, DFO, and bafilomycin A1 at their optimal concentrations and exposure times. Chronic ethanol consumption caused an evident increase in lysosomal redox-active iron accompanying sustained oxidative damage. Iron-mediated ROS could trigger lysosomal membrane permeabilization (LMP) and subsequent mitochondria apoptosis. The hepatotoxicity was attenuated by reducing lysosomal iron while being exacerbated by escalating lysosomal iron. Quercetin substantially alleviated the alcoholic liver oxidative damage and apoptosis by decreasing lysosome iron and ameliorating iron-mediated LMP, which provided a new prospective of the use of quercetin against ALD. PMID:27057276

  5. Quercetin Targets Cysteine String Protein (CSPα) and Impairs Synaptic Transmission

    PubMed Central

    Xu, Fenglian; Proft, Juliane; Gibbs, Sarah; Winkfein, Bob; Johnson, Jadah N.; Syed, Naweed; Braun, Janice E. A.

    2010-01-01

    Background Cysteine string protein (CSPα) is a synaptic vesicle protein that displays unique anti-neurodegenerative properties. CSPα is a member of the conserved J protein family, also called the Hsp40 (heat shock protein of 40 kDa) protein family, whose importance in protein folding has been recognized for many years. Deletion of the CSPα in mice results in knockout mice that are normal for the first 2–3 weeks of life followed by an unexplained presynaptic neurodegeneration and premature death. How CSPα prevents neurodegeneration is currently not known. As a neuroprotective synaptic vesicle protein, CSPα represents a promising therapeutic target for the prevention of neurodegenerative disorders. Methodology/Principal Findings Here, we demonstrate that the flavonoid quercetin promotes formation of stable CSPα-CSPα dimers and that quercetin-induced dimerization is dependent on the unique cysteine string region. Furthermore, in primary cultures of Lymnaea neurons, quercetin induction of CSPα dimers correlates with an inhibition of synapse formation and synaptic transmission suggesting that quercetin interfers with CSPα function. Quercetin's action on CSPα is concentration dependent and does not promote dimerization of other synaptic proteins or other J protein family members and reduces the assembly of CSPα:Hsc70 units (70kDa heat shock cognate protein). Conclusions/Significance Quercetin is a plant derived flavonoid and popular nutritional supplement proposed to prevent memory loss and altitude sickness among other ailments, although its precise mechanism(s) of action has been unclear. In view of the therapeutic promise of upregulation of CSPα and the undesired consequences of CSPα dysfunction, our data establish an essential proof of principle that pharmaceutical agents can selectively target the neuroprotective J protein CSPα. PMID:20548785

  6. Quercetin ameliorate insulin resistance and up-regulates cellular antioxidants during oleic acid induced hepatic steatosis in HepG2 cells.

    PubMed

    Vidyashankar, Satyakumar; Sandeep Varma, R; Patki, Pralhad Sadashiv

    2013-03-01

    Hepatic lipid accumulation and oxidative stress contribute to non-alcoholic fatty liver disease (NAFLD). Thus, we hypothesized that the hypolipidemic and antioxidant activity of quercetin would attenuate events leading to NAFLD. Addition of 2.0mM oleic acid (OA) into the culture media induced fatty liver condition in HepG2 cells by 24h. It was marked by significant accumulation of lipid droplets as determined by Oil-Red-O (ORO) based colorimetric assay, increased triacylglycerol (TAG) and increased lipid peroxidation. The inflammatory cytokines TNF-α and IL-8 levels were significantly increased with decreased antioxidant molecules. OA induced insulin resistance which was evident by inhibition of glucose uptake and cell proliferation. Quercetin (10 μM) increased cell proliferation by 3.05 folds with decreased TAG content (45%) and was effective in increasing insulin mediated glucose uptake by 2.65 folds. The intracellular glutathione content was increased by 2.0 folds without substantial increase in GSSG content. Quercetin (10 μM) decreased TNF-α and IL-8 by 59.74% and 41.11% respectively and inhibited generation of lipid peroxides by 50.5%. In addition, RT-PCR results confirmed quercetin (10 μM) inhibited TNF-alpha gene expression. Further, superoxide dismutase, catalase and glutathione peroxidase activities were increased by 1.68, 2.19 and 1.71 folds respectively. Albumin and urea content was increased while the alanine aminotransferase (ALAT) activity was significantly decreased by quercetin. Hence, quercetin effectively reversed NAFLD symptoms by decreased triacyl glycerol accumulation, insulin resistance, inflammatory cytokine secretion and increased cellular antioxidants in OA induced hepatic steatosis in HepG2 cells. PMID:23348005

  7. Quercetin ameliorate insulin resistance and up-regulates cellular antioxidants during oleic acid induced hepatic steatosis in HepG2 cells.

    PubMed

    Vidyashankar, Satyakumar; Sandeep Varma, R; Patki, Pralhad Sadashiv

    2013-03-01

    Hepatic lipid accumulation and oxidative stress contribute to non-alcoholic fatty liver disease (NAFLD). Thus, we hypothesized that the hypolipidemic and antioxidant activity of quercetin would attenuate events leading to NAFLD. Addition of 2.0mM oleic acid (OA) into the culture media induced fatty liver condition in HepG2 cells by 24h. It was marked by significant accumulation of lipid droplets as determined by Oil-Red-O (ORO) based colorimetric assay, increased triacylglycerol (TAG) and increased lipid peroxidation. The inflammatory cytokines TNF-α and IL-8 levels were significantly increased with decreased antioxidant molecules. OA induced insulin resistance which was evident by inhibition of glucose uptake and cell proliferation. Quercetin (10 μM) increased cell proliferation by 3.05 folds with decreased TAG content (45%) and was effective in increasing insulin mediated glucose uptake by 2.65 folds. The intracellular glutathione content was increased by 2.0 folds without substantial increase in GSSG content. Quercetin (10 μM) decreased TNF-α and IL-8 by 59.74% and 41.11% respectively and inhibited generation of lipid peroxides by 50.5%. In addition, RT-PCR results confirmed quercetin (10 μM) inhibited TNF-alpha gene expression. Further, superoxide dismutase, catalase and glutathione peroxidase activities were increased by 1.68, 2.19 and 1.71 folds respectively. Albumin and urea content was increased while the alanine aminotransferase (ALAT) activity was significantly decreased by quercetin. Hence, quercetin effectively reversed NAFLD symptoms by decreased triacyl glycerol accumulation, insulin resistance, inflammatory cytokine secretion and increased cellular antioxidants in OA induced hepatic steatosis in HepG2 cells.

  8. Quercetin-Imprinted Nanospheres as Novel Drug Delivery Devices

    PubMed Central

    Curcio, Manuela; Cirillo, Giuseppe; Parisi, Ortensia Ilaria; Iemma, Francesca; Picci, Nevio; Puoci, Francesco

    2012-01-01

    In this work, molecularly imprinted nanospheres for controlled/sustained release of quercetin were synthesized employing methacrylic acid and ethylene glycoldymethacrylate as functional monomer and crosslinking agent, respectively. One pot precipitation polymerization was chosen as polymerization technique to obtain nanosized materials with spherical shape. Morphological and hydrophilic properties by scanning electron microscopy and water content measurements were determined, and recognition and selectivity properties of the imprinted materials were tested using the template quercetin and its structural analogue, the flavonoid catechin. Finally, the applicability of the obtained materials as drug delivery devices was evaluated by performing in vitro release studies in plasma simulating fluids and cytotoxicity testson HeLa cells. PMID:24955531

  9. Production of 3-O-xylosyl quercetin in Escherichia coli.

    PubMed

    Pandey, Ramesh Prasad; Malla, Sailesh; Simkhada, Dinesh; Kim, Byung-Gee; Sohng, Jae Kyung

    2013-03-01

    Quercetin, a flavonol aglycone, is one of the most abundant flavonoids with high medicinal value. The bioavailability and pharmacokinetic properties of quercetin are influenced by the type of sugars attached to the molecule. To efficiently diversify the therapeutic uses of quercetin, Escherichia coli was harnessed as a production factory by the installation of various plant and bacterial UDP-xylose sugar biosynthetic genes. The genes encoding for the UDP-xylose pathway enzymes phosphoglucomutase (nfa44530), glucose-1-phosphate uridylyltransferase (galU), UDP-glucose dehydrogenase (calS8), and UDP-glucuronic acid decarboxylase (calS9) were overexpressed in E. coli BL21 (DE3) along with a glycosyltransferase (arGt-3) from Arabidopsis thaliana. Furthermore, E. coli BL21(DE3)/∆pgi, E. coli BL21(DE3)/∆zwf, E. coli BL21(DE3)/∆pgi∆zwf, and E. coli BL21(DE3)/∆pgi∆zwf∆ushA mutants carrying the aforementioned UDP-xylose sugar biosynthetic genes and glycosyltransferase and the galU-integrated E. coli BL21(DE3)/∆pgi host harboring only calS8, calS9, and arGt-3 were constructed to enhance whole-cell bioconversion of exogeneously supplied quercetin into 3-O-xylosyl quercetin. Here, we report the highest production of 3-O-xylosyl quercetin with E. coli BL21 (DE3)/∆pgi∆zwf∆ushA carrying UDP-xylose sugar biosynthetic genes and glycosyltransferase. The maximum concentration of 3-O-xylosyl quercetin achieved was 23.78 mg/L (54.75 μM), representing 54.75 % bioconversion, which was an ~4.8-fold higher bioconversion than that shown by E. coli BL21 (DE3) with the same set of genes when the reaction was carried out in 5-mL culture tubes with 100 μM quercetin under optimized conditions. Bioconversion was further improved by 98 % when the reaction was scaled up in a 3-L fermentor at 36 h. PMID:23053089

  10. Cadmium exposure during lactation causes learning and memory-impairment in F1 generation mice: amelioration by quercetin.

    PubMed

    Halder, Sumita; Kar, Rajarshi; Galav, Vikas; Mehta, Ashish K; Bhattacharya, Swapan K; Mediratta, Pramod K; Banerjee, Basu D

    2016-01-01

    Cadmium (Cd) is a known pollutant present in the environment at low levels and is reported to affect reproduction in many ways. The present study was undertaken to explore the effect of Cd in F1 generation mice on cognitive parameters, and to further investigate whether quercetin could modulate these effects. In this study, female lactating mice were exposed to cadmium for seven days just after delivery. The new born pups in their adulthood were tested for learning and memory parameters by passive avoidance task and Morris water maze (MWM) test. It was observed that pups exposed to Cd showed significant impairment of memory in step down latency test, which was reversed by quercetin (100 mg/kg). In MWM test for spatial memory, animals exposed to Cd exhibited increased escape latency, which was reversed by quercetin (50 mg/kg) significantly. Quercetin alone (50 and 100 mg/kg) also demonstrated improved spatial memory, and showed improved retention memory in the passive avoidance paradigm at dose 50 mg/kg. On testing oxidative stress parameters, we observed significantly increased malondialdehyde (MDA) levels in brain tissue of Cd-treated mice. Moreover, co-treatment with quercetin (50 mg/kg) and Cd significantly reduced these MDA levels. The other doses (25 and 100 mg/kg) also showed reduction in MDA levels as compared to the group exposed to Cd alone, though the difference was not statistically significant. Hence, this study highlights the possibility of cognitive impairment in adulthood if there is Cd exposure during lactation and oxidative stress could possibly attribute to this effect.

  11. Cadmium exposure during lactation causes learning and memory-impairment in F1 generation mice: amelioration by quercetin.

    PubMed

    Halder, Sumita; Kar, Rajarshi; Galav, Vikas; Mehta, Ashish K; Bhattacharya, Swapan K; Mediratta, Pramod K; Banerjee, Basu D

    2016-01-01

    Cadmium (Cd) is a known pollutant present in the environment at low levels and is reported to affect reproduction in many ways. The present study was undertaken to explore the effect of Cd in F1 generation mice on cognitive parameters, and to further investigate whether quercetin could modulate these effects. In this study, female lactating mice were exposed to cadmium for seven days just after delivery. The new born pups in their adulthood were tested for learning and memory parameters by passive avoidance task and Morris water maze (MWM) test. It was observed that pups exposed to Cd showed significant impairment of memory in step down latency test, which was reversed by quercetin (100 mg/kg). In MWM test for spatial memory, animals exposed to Cd exhibited increased escape latency, which was reversed by quercetin (50 mg/kg) significantly. Quercetin alone (50 and 100 mg/kg) also demonstrated improved spatial memory, and showed improved retention memory in the passive avoidance paradigm at dose 50 mg/kg. On testing oxidative stress parameters, we observed significantly increased malondialdehyde (MDA) levels in brain tissue of Cd-treated mice. Moreover, co-treatment with quercetin (50 mg/kg) and Cd significantly reduced these MDA levels. The other doses (25 and 100 mg/kg) also showed reduction in MDA levels as compared to the group exposed to Cd alone, though the difference was not statistically significant. Hence, this study highlights the possibility of cognitive impairment in adulthood if there is Cd exposure during lactation and oxidative stress could possibly attribute to this effect. PMID:26446883

  12. Quercetin Suppresses the Migration and Invasion in Human Colon Cancer Caco-2 Cells Through Regulating Toll-like Receptor 4/Nuclear Factor-kappa B Pathway

    PubMed Central

    Han, Mingyang; Song, Yucheng; Zhang, Xuedong

    2016-01-01

    Objective: The migration and invasion features, which were associated with inflammatory response, acted as vital roles in the development of colon cancer. Quercetin, a bioflavonoid compound, was widely spread in vegetables and fruits. Although quercetin exerts antioxidant and anticancer activities, the molecular signaling pathways in human colon cancer cells remain unclear. Hence, the present study was conducted to investigate the suppression of quercetin on migratory and invasive activity of colon cancer and the underlying mechanism. Materials and Methods: The effect of quercetin on cell viability, migration, and invasion of Caco-2 cells was analyzed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, wound-healing assay, and transwell chambers assay, respectively. The protein expressions of toll-like receptor 4 (TLR4), nuclear factor-kappa B (NF-κB) p65, mitochondrial membrane potential-2 (MMP-2), and MMP-9 were detected by Western blot assay. The inflammatory factors, such as tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (Cox-2), and interleukin-6 (IL-6), in cell supernatant were detected by enzyme-linked immunosorbent assay. Results: The concentration of quercetin <20 μM was chosen for further experiments. Quercetin (5 μM) could remarkably suppress the migratory and invasive capacity of Caco-2 cells. The expressions of metastasis-related proteins of MMP-2, MMP-9 were decreased, whereas the expression of E-cadherin protein was increased by quercetin in a dose-dependent manner. Interestingly, the anti-TLR4 (2 μg) antibody or pyrrolidine dithiocarbamate (PDTC; 1 μM) could affect the inhibition of quercetin on cell migration and invasion, as well as the protein expressions of MMP-2, MMP-9, E-cadherin, TLR4, and NF-κB p65. In addition, quercetin could reduce the inflammation factors production of TNF-α, Cox-2, and IL-6. Conclusion: The findings suggested for the 1st time that quercetin might exert its anticolon cancer activity via

  13. Increased expression of Slit2 and its receptors Robo1 and Robo4 in reactive astrocytes of the rat hippocampus after transient forebrain ischemia.

    PubMed

    Park, Joo-Hee; Pak, Ha-Jin; Riew, Tae-Ryong; Shin, Yoo-Jin; Lee, Mun-Yong

    2016-03-01

    Slit2 is a secreted glycoprotein that was originally identified as a chemorepulsive factor in the developing brain; however, it was recently reported that Slit2 is associated with adult neuronal function including a variety of pathophysiological processes. To elucidate whether Slit2 is implicated in the pathophysiology of ischemic injury, we investigated the temporal changes and cellular localization of Slit2 and its predominant receptors, Robo1 and Robo4, for 28 days after transient forebrain ischemia. Slit2 and its receptors had similar overall expression patterns in the control and ischemic hippocampi. The ligand and receptors were constitutively expressed in hippocampal neurons in control animals; however, in animals with ischemic injury, their upregulation was detected in reactive astrocytes, but not in neurons or activated microglia, in the CA1 region. Astroglial induction of Slit2 and its receptors occurred by day 3 after reperfusion, and appeared to increase progressively until the final time point on day 28. Their temporal expression patterns overlapped with the time period in which reactive astrocytes undergo dynamic structural changes and appear hypertrophic in the ischemic hippocampus. The immunohistochemical data were consistent with the results of the immunoblot analyses, indicating that the expression of Slit2 and Robo increased progressively over the relatively long period of 28 days examined here. Collectively, these results suggest that Slit2/Robo signaling may be involved in regulating the astroglial reaction via autocrine or paracrine mechanisms in post-ischemic processes. Moreover, this may contribute to the dynamic morphological changes that occur in astrocytes in response to ischemic injury.

  14. Transient Increased Calcium and Calcitriol Requirements After Discontinuation of Human Synthetic Parathyroid Hormone 1-34 (hPTH 1-34) Replacement Therapy in Hypoparathyroidism.

    PubMed

    Gafni, Rachel I; Guthrie, Lori C; Kelly, Marilyn H; Brillante, Beth A; Christie, C Michele; Reynolds, James C; Yovetich, Nancy A; James, Robert; Collins, Michael T

    2015-11-01

    Synthetic human PTH 1-34 (hPTH 1-34) replacement therapy in hypoparathyroidism maintains eucalcemia and converts quiescent bone to high-turnover bone. However, the skeletal and metabolic effects of drug discontinuation have not been reported. Nine subjects with hypoparathyroidism received subcutaneous injections of hPTH 1-34 two to three times daily for 19.8 to 61.3 months and then transitioned back to calcium and calcitriol. Biochemistries and bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) were assessed at baseline, while on treatment, and at follow-up 3 to 12 months after drug discontinuation. Two subjects developed hypocalcemia when hPTH 1-34 was abruptly discontinued. Thus, to avoid hypocalcemia, subjects were slowly weaned from hPTH 1-34 over several weeks. When hPTH 1-34 was stopped, subjects were requiring two to three times pretreatment doses of calcitriol and calcium to maintain blood calcium levels. Doses were gradually reduced over many weeks until calcium levels were stable on doses similar to baseline. Bone-specific alkaline phosphatase (BSAP), N-telopeptide (NTX), and osteocalcin (OC) increased significantly with hPTH 1-34; at follow-up, BSAP and NTX had returned to baseline while OC was still slightly elevated. During treatment, BMD was unchanged at the hip and lateral spine but declined at the anterior-posterior (AP) spine, radius, and total body. During weaning, BMD increased, with the hip and lateral spine exceeding pre-hPTH 1-34 values and the whole body returning to baseline. AP spine was increased non-significantly compared to baseline at follow-up. hPTH 1-34 must be gradually weaned in hypoparathyroid patients with high doses of oral medications given to avoid hypocalcemia. The transient increased requirements accompanied by increased BMD after long-term hPTH 1-34 therapy suggest a reversal of the expanded remodeling space favoring bone formation as the skeleton returns to a low-turnover state, reminiscent of the hungry

  15. Estimated daily intake and seasonal food sources of quercetin in Japan.

    PubMed

    Nishimuro, Haruno; Ohnishi, Hirofumi; Sato, Midori; Ohnishi-Kameyama, Mayumi; Matsunaga, Izumi; Naito, Shigehiro; Ippoushi, Katsunari; Oike, Hideaki; Nagata, Tadahiro; Akasaka, Hiroshi; Saitoh, Shigeyuki; Shimamoto, Kazuaki; Kobori, Masuko

    2015-04-01

    Quercetin is a promising food component, which can prevent lifestyle related diseases. To understand the dietary intake of quercetin in the subjects of a population-based cohort study and in the Japanese population, we first determined the quercetin content in foods available in the market during June and July in or near a town in Hokkaido, Japan. Red leaf lettuce, asparagus, and onions contained high amounts of quercetin derivatives. We then estimated the daily quercetin intake by 570 residents aged 20-92 years old in the town using a food frequency questionnaire (FFQ). The average and median quercetin intakes were 16.2 and 15.5 mg day(-1), respectively. The quercetin intakes by men were lower than those by women; the quercetin intakes showed a low correlation with age in both men and women. The estimated quercetin intake was similar during summer and winter. Quercetin was mainly ingested from onions and green tea, both in summer and in winter. Vegetables, such as asparagus, green pepper, tomatoes, and red leaf lettuce, were good sources of quercetin in summer. Our results will help to elucidate the association between quercetin intake and risks of lifestyle-related diseases by further prospective cohort study and establish healthy dietary requirements with the consumption of more physiologically useful components from foods. PMID:25849945

  16. Estimated Daily Intake and Seasonal Food Sources of Quercetin in Japan

    PubMed Central

    Nishimuro, Haruno; Ohnishi, Hirofumi; Sato, Midori; Ohnishi-Kameyama, Mayumi; Matsunaga, Izumi; Naito, Shigehiro; Ippoushi, Katsunari; Oike, Hideaki; Nagata, Tadahiro; Akasaka, Hiroshi; Saitoh, Shigeyuki; Shimamoto, Kazuaki; Kobori, Masuko

    2015-01-01

    Quercetin is a promising food component, which can prevent lifestyle related diseases. To understand the dietary intake of quercetin in the subjects of a population-based cohort study and in the Japanese population, we first determined the quercetin content in foods available in the market during June and July in or near a town in Hokkaido, Japan. Red leaf lettuce, asparagus, and onions contained high amounts of quercetin derivatives. We then estimated the daily quercetin intake by 570 residents aged 20–92 years old in the town using a food frequency questionnaire (FFQ). The average and median quercetin intakes were 16.2 and 15.5 mg day−1, respectively. The quercetin intakes by men were lower than those by women; the quercetin intakes showed a low correlation with age in both men and women. The estimated quercetin intake was similar during summer and winter. Quercetin was mainly ingested from onions and green tea, both in summer and in winter. Vegetables, such as asparagus, green pepper, tomatoes, and red leaf lettuce, were good sources of quercetin in summer. Our results will help to elucidate the association between quercetin intake and risks of lifestyle-related diseases by further prospective cohort study and establish healthy dietary requirements with the consumption of more physiologically useful components from foods. PMID:25849945

  17. Anti Proliferative and Pro Apoptotic Effects of Flavonoid Quercetin Are Mediated by CB1 Receptor in Human Colon Cancer Cell Lines.

    PubMed

    Refolo, Maria Grazia; D'Alessandro, Rosalba; Malerba, Natascia; Laezza, Chiara; Bifulco, Maurizio; Messa, Caterina; Caruso, Maria Gabriella; Notarnicola, Maria; Tutino, Valeria

    2015-12-01

    Quercetin, the major constituent of flavonoid and widely present in fruits and vegetables, is an attractive compound for cancer prevention due to its beneficial anti proliferative effects, showing a crucial role in the regulation of apoptosis and cell cycle signaling. In vitro studies have demonstrated that quercetin specifically influences colon cancer cell proliferation. Our experiments, using human colon adenocarcinoma cells, confirmed the anti proliferative effect of quercetin and gave intriguing new insight in to the knowledge of the mechanisms involved. We observed a significant increase in the expression of the endocannabinoids receptor (CB1-R) after quercetin treatment. CB1-R can be considered an estrogen responsive receptor and quercetin, having a structure similar to that of the estrogens, can interact with CB1-R leading to the regulation of cell growth. In order to clarify the contribution of the CB1-R to the quercetin action, we investigated some of the principal molecular pathways that are inhibited or activated by this natural compound. In particular we detected the inhibition of the major survival signals like the PI3K/Akt/mTOR and an induction of the pro apoptotic JNK/JUN pathways. Interestingly, the metabolism of β-catenin was modified by flavonoid both directly and through activated CB1-R. In all the experiments done, the quercetin action has proven to be reinforced by anandamide (Met-F-AEA), a CB1-R agonist, and partially counteracted by SR141716, a CB1-R antagonist. These findings open new perspectives for anticancer therapeutic strategies.

  18. Quercetin Attenuates Inflammatory Responses in BV-2 Microglial Cells: Role of MAPKs on the Nrf2 Pathway and Induction of Heme Oxygenase-1

    PubMed Central

    Sun, Grace Y.; Chen, Zihong; Jasmer, Kimberly J.; Chuang, Dennis Y.; Gu, Zezong; Hannink, Mark; Simonyi, Agnes

    2015-01-01

    A large group of flavonoids found in fruits and vegetables have been suggested to elicit health benefits due mainly to their anti-oxidative and anti-inflammatory properties. Recent studies with immune cells have demonstrated inhibition of these inflammatory responses through down-regulation of the pro-inflammatory pathway involving NF-κB and up-regulation of the anti-oxidative pathway involving Nrf2. In the present study, the murine BV-2 microglial cells were used to compare anti-inflammatory activity of quercetin and cyanidin, two flavonoids differing by their alpha, beta keto carbonyl group. Quercetin was 10 folds more potent than cyanidin in inhibition of lipopolysaccharide (LPS)-induced NO production as well as stimulation of Nrf2-induced heme-oxygenase-1 (HO-1) protein expression. In addition, quercetin demonstrated enhanced ability to stimulate HO-1 protein expression when cells were treated with LPS. In an attempt to unveil mechanism(s) for quercetin to enhance Nrf2/HO-1 activity under endotoxic stress, results pointed to an increase in phospho-p38MAPK expression upon addition of quercetin to LPS. In addition, pharmacological inhibitors for phospho-p38MAPK and MEK1/2 for ERK1/2 further showed that these MAPKs target different sites of the Nrf2 pathway that regulates HO-1 expression. However, inhibition of LPS-induced NO by quercetin was not fully reversed by TinPPIX, a specific inhibitor for HO-1 activity. Taken together, results suggest an important role of quercetin to regulate inflammatory responses in microglial cells and its ability to upregulate HO-1 against endotoxic stress through involvement of MAPKs. PMID:26505893

  19. Quercetin ameliorates ischemia/reperfusion-induced cognitive deficits by inhibiting ASK1/JNK3/caspase-3 by enhancing the Akt signaling pathway.

    PubMed

    Pei, Bing; Yang, Miaomiao; Qi, Xiaoyan; Shen, Xin; Chen, Xing; Zhang, Fayong

    2016-09-01

    Cerebral ischemia/reperfusion (I/R) is a major cause of severe disability and death all worldwide. However, therapeutic options to minimize the detrimental effects of cerebral I/R injury are limited. Recent research has demonstrated that quercetin mediates neuroprotective effects associated with the activation of the Akt signaling pathway in the cerebral I/R brain. Therefore, the aim of this study was to further investigate the mechanisms of cognitive deficits induced by cerebral I/R injury and the effects of quercetin on these mechanisms. First, we assessed anxiety-like behavioral and cognitive impairment using the open field test and the Morris water maze test, respectively. Next, we examined the severity of apoptosis by staining hippocampal neurons by the Cresyl violet method. Third, we used western blot analysis to investigate the expression of total and phosphorylated Akt, ASK1, JNK3, c-Jun and caspase-3 after I/R injury. Our results revealed that mice subjected to bilateral common carotid occlusion exhibited severe anxiety-like behavior, learning and memory impairment, cell damage and apoptosis. These severe effects were attenuated by administration of quercetin. Further, western blot analysis revealed that quercetin increased p-Akt expression and decreased p-ASK1, p-JNK3 and cleaved caspase-3 expression after cerebral I/R injury and led to inhibition of neuronal apoptosis. Conversely, treatment with LY294002 (a selective inhibitor of Akt1) reversed the effects of quercetin. In conclusion, these findings highlight the important role of quercetin in protecting against cognitive deficits and inhibiting neuronal apoptosis via the Akt signaling pathway. We believe that quercetin might prove to be a useful therapeutic component in treating cerebral I/R diseases in the near future. PMID:27450812

  20. Quercetin stabilizes apolipoprotein E and reduces brain Aβ levels in amyloid model mice.

    PubMed

    Zhang, Xilin; Hu, Jin; Zhong, Li; Wang, Na; Yang, Longyu; Liu, Chia-Chen; Li, Huifang; Wang, Xin; Zhou, Ying; Zhang, Yunwu; Xu, Huaxi; Bu, Guojun; Zhuang, Jiangxing

    2016-09-01

    Apolipoprotein E (apoE) is a major cholesterol carrier that regulates lipid homeostasis by mediating lipid transport from one tissue or cell type to another. In the central neural system (CNS), apoE is mainly produced by astrocytes, and transports cholesterol to neurons via apoE receptors, which are members of the low-density lipoprotein receptor family. The APOEε4 gene is a strong genetic risk factor for late-onset sporadic Alzheimer's disease (AD), likely through its strong effect on the accumulation of amyloid-β (Aβ) peptide. ApoE protein levels in cerebrospinal fluid (CSF) and plasma are reduced in APOEε4 carriers and in patients with AD. Furthermore, altered cholesterol levels are also associated with the risk of AD. Aβ accumulation, oligomerization and deposition in the brain are central to the pathogenesis of AD. Mounting evidence demonstrates that apoE and apoE receptors play important roles in these processes. Astrocyte-derived apoE is pivotal for cerebral cholesterol metabolism and clearance of Aβ. Thus, we hypothesized that increased apoE in the brain may be an effective therapeutic strategy for AD. We report here that quercetin can significantly increase apoE levels by inhibiting apoE degradation in immortalized astrocytes. Importantly, we show that oral administration of quercetin significantly increased brain apoE and reduced insoluble Aβ levels in the cortex of 5xFAD amyloid model mice. Our results demonstrate that quercetin increases apoE levels through a novel mechanism and can be explored as a novel class of drug for AD therapy. PMID:27114256

  1. A transient increase in lipid peroxidation primes preadipocytes for delayed mitochondrial inner membrane permeabilization and ATP depletion during prolonged exposure to fatty acids

    PubMed Central

    Rogers, Carlyle; Davis, Barbara; Neufer, P. Darrell; Murphy, Michael P.; Anderson, Ethan J; Robidoux, Jacques

    2014-01-01

    Preadipocytes are periodically subjected to fatty acid (FA) concentrations that are potentially cytotoxic. We tested the hypothesis that prolonged exposure of preadipocytes of human origin to a physiologically relevant mix of FAs leads to mitochondrial inner membrane (MIM) permeabilization and ultimately to mitochondrial crisis. We found that exposure of preadipocytes to FAs led to progressive cyclosporin A-sensitive MIM permeabilization, which in turn caused reduction in MIM potential (ΔΨM), oxygen consumption, ATP synthetic capacity, and ultimately death. Additionally, we showed that FAs induce a transient increase in intramitochondrial ROS and lipid peroxide production lasting roughly 30 and 120 minutes for the ROS and lipid peroxides, respectively. MIM permeabilization and its deleterious consequences including mitochondrial crisis and cell death were prevented by treating the cells with the mitochondrial FA uptake inhibitor, Etomoxir; the mitochondrion selective superoxide and lipid peroxide antioxidants, MitoTempo and MitoQ; or the lipid peroxide and reactive carbonyl scavenger, L-carnosine. FAs also promoted a delayed oxidative stress phase. However, since the beneficial effects of Etomoxir, MitoTempo and L-carnosine were lost by delaying the treatment by 2 hours, it suggested that the initial phase was sufficient to prime the cells for the delayed MIM permeabilization and mitochondrial crisis. It also suggested that the second ROS production phase is a consequence of this loss in mitochondrial health. Altogether, our data suggest that approaches designed to diminish intramitochondrial ROS or lipid peroxide accumulation as well as MIM permeabilization, are valid mechanism-based therapeutic avenues to prevent the loss in preadipocyte metabolic fitness associated with prolonged exposure to elevated FA levels. PMID:24269897

  2. Ingestion of a carbonated beverage decreases lower esophageal sphincter pressure and increases frequency of transient lower esophageal sphincter relaxation in normal subjects.

    PubMed

    Shukla, Akash; Meshram, Megha; Gopan, Amrit; Ganjewar, Vaibhav; Kumar, Praveen; Bhatia, Shobna J

    2012-06-01

    Transient lower esophageal sphincter relaxation (tLESR) and decreased basal lower esophageal sphincter (LES) pressure are postulated mechanisms of gastroesophageal reflux (GER). There is conflicting evidence on the effect of carbonated drinks on lower esophageal sphincter function. This study was conducted to assess the effect of a carbonated beverage on tLESR and LES pressure. High resolution manometry tracings (16 channel water-perfused, Trace 1.2, Hebbard, Australia) were obtained in 18 healthy volunteers (6 men) for 30 min each at baseline, and after 200 mL of chilled potable water and 200 mL of chilled carbonated cola drink (Pepsi [Pepsico India Ltd]). The sequence of administration of the drinks was determined by random number method generated by a computer. The analysis of tracings was done using TRACE 1.2 software by a physician who was unaware of the sequence of administration of fluids. The mean (SD) age of the participant was 37.3 (12.9) years. The median (range) frequency of tLESr was higher after the carbonated beverage (10.5 [0-26]) as compared to baseline (0 [0-3], p = 0.005) as well as after water (1 [0-14], p = 0.010). The LES pressure decreased after ingestion of the carbonated beverage (18.5 [11-37] mmHg) compared to baseline (40.5 [25-66] mmHg, p = 0.0001) and after water (34 [15-67] mmHg, p = 0.003). Gastric pressure was not different in the three groups. Ingestion of a carbonated beverage increases tLESr and lowers LES pressure in healthy subjects.

  3. Chronic ethanol ingestion during puberty alters the transient increase in testicular 5 alpha-reductase in the Swiss-Webster mouse.

    PubMed

    Anderson, R A; Phillips, J F; Zaneveld, L J

    1989-01-01

    Previous experiments with inbred mice showed that chronic ethanol treatment delays male pubertal development. An initial event in sexual maturation in the rat is a transient increase in 5 alpha-reductase. The present study was conducted to determine whether similar ethanol effects occur in outbred mice (Swiss-Webster), to determine the ontological profile of testicular 5 alpha-reductase in the mouse, and to evaluate the effect of ethanol treatment on this enzyme. After 29 days of treatment with a liquid diet (beginning at age 20 days), reductions in the ethanol-treated mice as compared with the controls were noted in testicular weight (55.0 +/- 2.0 vs. 63.0 +/- 2.4 mg; P less than 0.01), epididymal sperm content (6.8 X 10(5) vs. 14.4 X 10(5); P less than 0.05), and sperm motility (45% vs. 57%; P less than 0.05). After 43 days, differences no longer existed. In chow-fed mice, a substantial rise in 5 alpha-reductase (1 unit = 1 pmole DHT formed/45 min/mg testis) began at age 24 days. Activity peaked at approximately 65 units at 25 to 30 days and gradually declined to 6.4 +/- 0.8 units at 63 days. After 29 days treatment, 5 alpha-reductase of the pair-fed control group was 26.8 +/- 4.9 units, which decreased to a baseline value of 7.0 +/- 2.1 units after 43 days treatment. In contrast, 5 alpha-reductase of the ethanol-treated group remained at baseline levels after 29 days (7.7 +/- 2.3 units) and 43 days of treatment (7.6 +/- 2.3 units).(ABSTRACT TRUNCATED AT 250 WORDS)

  4. Ingestion of a carbonated beverage decreases lower esophageal sphincter pressure and increases frequency of transient lower esophageal sphincter relaxation in normal subjects.

    PubMed

    Shukla, Akash; Meshram, Megha; Gopan, Amrit; Ganjewar, Vaibhav; Kumar, Praveen; Bhatia, Shobna J

    2012-06-01

    Transient lower esophageal sphincter relaxation (tLESR) and decreased basal lower esophageal sphincter (LES) pressure are postulated mechanisms of gastroesophageal reflux (GER). There is conflicting evidence on the effect of carbonated drinks on lower esophageal sphincter function. This study was conducted to assess the effect of a carbonated beverage on tLESR and LES pressure. High resolution manometry tracings (16 channel water-perfused, Trace 1.2, Hebbard, Australia) were obtained in 18 healthy volunteers (6 men) for 30 min each at baseline, and after 200 mL of chilled potable water and 200 mL of chilled carbonated cola drink (Pepsi [Pepsico India Ltd]). The sequence of administration of the drinks was determined by random number method generated by a computer. The analysis of tracings was done using TRACE 1.2 software by a physician who was unaware of the sequence of administration of fluids. The mean (SD) age of the participant was 37.3 (12.9) years. The median (range) frequency of tLESr was higher after the carbonated beverage (10.5 [0-26]) as compared to baseline (0 [0-3], p = 0.005) as well as after water (1 [0-14], p = 0.010). The LES pressure decreased after ingestion of the carbonated beverage (18.5 [11-37] mmHg) compared to baseline (40.5 [25-66] mmHg, p = 0.0001) and after water (34 [15-67] mmHg, p = 0.003). Gastric pressure was not different in the three groups. Ingestion of a carbonated beverage increases tLESr and lowers LES pressure in healthy subjects. PMID:22791463

  5. A novel mechanism for the promotion of quercetin glycoside absorption by megalo α-1,6-glucosaccharide in the rat small intestine.

    PubMed

    Shinoki, Aki; Lang, Weeranuch; Thawornkuno, Charin; Kang, Hee-Kwon; Kumagai, Yuya; Okuyama, Masayuki; Mori, Haruhide; Kimura, Atsuo; Ishizuka, Satoshi; Hara, Hiroshi

    2013-01-15

    The presence of an α-1,6-glucosaccharide enhances absorption of water-soluble quercetin glycosides, a mixture of quercetin-3-O-β-d-glucoside (Q3G, 31.8%), mono (23.3%), di (20.3%) and more d-glucose adducts with α-1,4-linkage to a d-glucose moiety of Q3G, in a ligated small intestinal loop of anesthetized rats. We prepared α-1,6-glucosaccharides with different degrees of polymerization (DP) enzymatically and separated them into a megalo-isomaltosaccharide-containing fraction (M-IM, average DP=11.0) and an oligo-isomaltosaccharide-containing fraction (O-IM, average DP=3.6). Luminal injection of either saccharide fraction promoted the absorption of total quercetin-derivatives from the small intestinal segment and this effect was greater for M-IM than O-IM addition. M-IM also increased Q3G, but not the quercetin aglycone, concentration in the water-phase of the luminal contents more strongly than O-IM. The enhancement of Q3G solubilization in the luminal contents may be responsible for the increases in the quercetin glucoside absorption promoted by α-1,6-glucosaccharides, especially that by M-IM. These results suggest that the ingestion of α-1,6-glucosaccharides promotes Q3G bioavailability.

  6. Rutin and quercetin show greater efficacy than nifedipin in ameliorating hemodynamic, redox, and metabolite imbalances in sodium chloride-induced hypertensive rats.

    PubMed

    Olaleye, M T; Crown, O O; Akinmoladun, A C; Akindahunsi, A A

    2014-06-01

    Rutin and quercetin were investigated for their effects on blood pressure and antioxidant defense system of rats fed with 8% sodium chloride-supplemented diet (high salt diet) for 6 weeks. Animals fed with high salt diet demonstrated an increase in systolic, diastolic, pulse, and mean arterial blood pressures (p < 0.05) as well as lipid peroxidation but decreases in the activities of antioxidant enzymes compared with control group. Groups post-treated with rutin and quercetin for 2 weeks showed significant reversals in the values of these indices compared with the group fed with only the high salt diet but not post-treated. The high salt diet also led to significant increase in serum glucose, urea, creatinine, triglycerides, low-density-lipoprotein, and total cholesterol concentrations. Treatment with rutin and quercetin ameliorated the effects of high salt diet on these biochemical indices. The reference standard, nifedipin was less effective than rutin and quercetin. The results of this study highlight the risk of high salt consumption on cardiovascular health and the potent antioxidant and antihypertensive property of rutin and quercetin.

  7. Intracellular metabolism and bioactivity of quercetin and its in vivo metabolites.

    PubMed Central

    Spencer, Jeremy P E; Kuhnle, Gunter G C; Williams, Robert J; Rice-Evans, Catherine

    2003-01-01

    Understanding the cellular effects of flavonoid metabolites is important for predicting which dietary flavonoids might be most beneficial in vivo. Here we investigate the bioactivity in dermal fibroblasts of the major reported in vivo metabolites of quercetin, i.e. 3'-O-methyl quercetin, 4'-O-methyl quercetin and quercetin 7-O-beta-D-glucuronide, relative to that of quercetin, in terms of their further metabolism and their resulting cytotoxic and/or cytoprotective effects in the absence and presence of oxidative stress. Uptake experiments indicate that exposure to quercetin led to the generation of two novel cellular metabolites, one characterized as a 2'-glutathionyl quercetin conjugate and another product with similar spectral characteristics but 1 mass unit lower, putatively a quinone/quinone methide. A similar product was identified in cells exposed to 3'-O-methyl quercetin, but not in the lysates of those exposed to its 4'-O-methyl counterpart, suggesting that its formation is related to oxidative metabolism. There was no uptake or metabolism of quercetin 7-O-beta-D-glucuronide by fibroblasts. Formation of oxidative metabolites may explain the observed concentration-dependent toxicity of quercetin and 3'-O-methyl quercetin, whereas the formation of a 2'-glutathionyl quercetin conjugate is interpreted as a detoxification step. Both O -methylated metabolites conferred less protection than quercetin against peroxide-induced damage, and quercetin glucuronide was ineffective. The ability to modulate cellular toxicity paralleled the ability of the compounds to decrease the level of peroxide-induced caspase-3 activation. Our data suggest that the actions of quercetin and its metabolites in vivo are mediated by intracellular metabolites. PMID:12578560

  8. DFT study of glycosyl group reactivity in quercetin derivatives

    NASA Astrophysics Data System (ADS)

    Jeevitha, D.; Sadasivam, K.; Praveena, R.; Jayaprakasam, R.

    2016-09-01

    Density functional theory (DFT) is used to compute relevant electronic properties with the purpose of generating precise information which facilitates the best activity given by the positions of glycosyl group attached at all 3 different rings of quercetin such as Q3G (C- ring), Q7G (A-ring) and Q3‧G (B-ring). Computed values of the OH BDE, frontier molecular orbitals (FMOs), molecular electrostatic potential (MEP), Density of states (DOS,PDOS,OPDOS) and electronic properties such as electron affinity (EA), ionization potential (IP), softness (S), hardness (η), electronegativity (χ) and electrophilic index (ω) indicate that the title compounds possess good radical scavenging activity. Charge delocalization and intramolecular hydrogen bonds are characterized using natural bond orbital (NBO) analysis. NBO accurately differentiate the weak and strong intramolecular hydrogen bond of quercetin-O-glycoside compounds. Results available from the computational investigation have proved that A-ring glycoside of quercetin is capable of donating electrons and acts as a good anti-oxidant than B-ring glycoside and C-ring glycoside of quercetin.

  9. Quercetin as colorimetric reagent for determination of zirconium

    USGS Publications Warehouse

    Grimaldi, F.S.; White, C.E.

    1953-01-01

    Methods described in the literature for the determination of zirconium are generally designed for relatively large amounts of this element. A good procedure using colorimetric reagent for the determination of trace amounts is desirable. Quercetin has been found to yield a sensitive color reaction with zirconium suitable for the determination of from 0.1 to 50?? of zirconium dioxide. The procedure developed involves the separation of zirconium from interfering elements by precipitation with p-dimethylaminoazophenylarsonic acid prior to its estimation with quercetin. The quercetin reaction is carried out in 0.5N hydrochloric acid solution. Under the operating conditions it is indicated that quercetin forms a 2 to 1 complex with zirconium; however, a 2 to 1 and a 1 to 1 complex can coexist under special conditions. Approximate values for the equilibrium constants of the complexes are K1 = 0.33 ?? 10-5 and K2 = 1.3 ?? 10-9. Seven Bureau of Standards samples of glass sands and refractories were analyzed with excellent results. The method described should find considerable application in the analysis of minerals and other materials for macro as well as micro amounts of zirconium.

  10. Global SUMOylation facilitates the multimodal neuroprotection afforded by quercetin against the deleterious effects of oxygen/glucose deprivation and the restoration of oxygen/glucose.

    PubMed

    Lee, Yang-Ja; Bernstock, Joshua D; Nagaraja, Nandakumar; Ko, Brian; Hallenbeck, John M

    2016-07-01

    The putative neuroprotective properties of various flavonoids have long been reported. Among this class of chemicals, quercetin, a major flavone/flavonol naturally occurring in plants, deserves focused attention because of the myriad of beneficial effects observed in various in vitro and in vivo models of central nervous system damage/degeneration. However, the mechanisms governing the beneficial outcomes mediated by quercetin remain to be elucidated. In an effort to define the underlying molecular mechanisms, our study employed human/rat neuroblastoma cell lines (SHSY5Y and B35, respectively) and E18-derived rat primary cortical neurons upon which the effects of various flavonoids were examined. Of note, increases in the levels of global SUMOylation, a post-translational modification with the Small Ubiquitin-like MOdifier (SUMO) were pronounced. Quercetin treatment increased SUMOylation levels in both SHSY5Y cells and rat cortical neurons in a dose and time-dependent manner, possibly via the direct inactivation of certain SENPs (SUMO-specific isopeptidases). Of particular interest, cells treated with quercetin displayed increased tolerance to oxygen/glucose deprivation exposure, an in vitro model of ischemia. SHSY5Y cells treated with quercetin also increased the expression of Nrf2 (via a decrease in the levels of Keap1), heme oxygenase-1 (HO-1), and nitric oxide synthase 1 (NOS1), which provide further protection from oxidative stress. In addition, the increased SUMOylation of HIF-1α was noted and deemed to be significant. We hypothesize that SUMOylated HIF-1α plays a fundamental role in the protection afforded and may underlie some of quercetin's ability to protect cells from oxygen/glucose deprivation-induced cell death, via an up-regulation of HO-1 and NOS1, which ultimately leads to the induction of pro-life NOS1/protein kinase G signaling. Quercetin acts to increase survival in the face of ischemia via an increase of SENP3 expression, the possible

  11. The BPV-4 co-carcinogen quercetin induces cell cycle arrest and up-regulates transcription from the LCR of BPV-4.

    PubMed

    Connolly, J A; Morgan, I M; Jackson, M E; Campo, M S

    1998-05-28

    Bracken fern is the environmental co-carcinogen of BPV-4 in the induction of neoplasias of the upper alimentary canal of cattle. The flavonoid quercetin is one of the most potent and best characterised mutagens present in the fern. We have shown that transfection with BPV-4 DNA and exposure to a single dose of quercetin leads to tumorigenic transformation of primary bovine cells. We now show that quercetin induces cell cycle arrest and up-regulates transcription from the BPV-4 long control region (LCR). This up-regulation is mediated by a 21 nucleotide-long cis-element in the LCR, designated QRE-1, which is located immediately downstream of the TATA box. Cellular proteins bind to QRE-1 and removal or substitution of QRE-1 lead to the abrogation of the response to quercetin. As expression of the viral oncogenes is controlled by the LCR, perturbation in this control and increased oncoprotein expression are likely to contribute to fully malignant cell transformation by overcoming the cell cycle arrest induced by quercetin, thus forcing damaged cells to proliferate.

  12. Quercetin Protects against Okadaic Acid-Induced Injury via MAPK and PI3K/Akt/GSK3β Signaling Pathways in HT22 Hippocampal Neurons.

    PubMed

    Jiang, Wei; Luo, Tao; Li, Sheng; Zhou, Yue; Shen, Xiu-Yin; He, Feng; Xu, Jie; Wang, Hua-Qiao

    2016-01-01

    Increasing evidence shows that oxidative stress and the hyperphosphorylation of tau protein play essential roles in the progression of Alzheimer's disease (AD). Quercetin is a major flavonoid that has anti-oxidant, anti-cancer and anti-inflammatory properties. We investigated the neuroprotective effects of quercetin to HT22 cells (a cell line from mouse hippocampal neurons). We found that Okadaic acid (OA) induced the hyperphosphorylation of tau protein at Ser199, Ser396, Thr205, and Thr231 and produced oxidative stress to the HT22 cells. The oxidative stress suppressed the cell viability and decreased the levels of lactate dehydrogenase (LDH), superoxide dismutase (SOD), mitochondria membrane potential (MMP) and Glutathione peroxidase (GSH-Px). It up-regulated malondialdehyde (MDA) production and intracellular reactive oxygen species (ROS). In addition, phosphoinositide 3 kinase/protein kinase B/Glycogen synthase kinase3β (PI3K/Akt/GSK3β) and mitogen activated protein kinase (MAPK) were also involved in this process. We found that pre-treatment with quercetin can inhibited OA-induced the hyperphosphorylation of tau protein and oxidative stress. Moreover, pre-treatment with quercetin not only inhibited OA-induced apoptosis via the reduction of Bax, and up-regulation of cleaved caspase 3, but also via the inhibition of PI3K/Akt/GSK3β, MAPKs and activation of NF-κB p65. Our findings suggest the therapeutic potential of quercetin to treat AD. PMID:27050422

  13. Quercetin Protects against Okadaic Acid-Induced Injury via MAPK and PI3K/Akt/GSK3β Signaling Pathways in HT22 Hippocampal Neurons

    PubMed Central

    Li, Sheng; Zhou, Yue; Shen, Xiu-Yin; He, Feng; Xu, Jie; Wang, Hua-Qiao

    2016-01-01

    Increasing evidence shows that oxidative stress and the hyperphosphorylation of tau protein play essential roles in the progression of Alzheimer’s disease (AD). Quercetin is a major flavonoid that has anti-oxidant, anti-cancer and anti-inflammatory properties. We investigated the neuroprotective effects of quercetin to HT22 cells (a cell line from mouse hippocampal neurons). We found that Okadaic acid (OA) induced the hyperphosphorylation of tau protein at Ser199, Ser396, Thr205, and Thr231 and produced oxidative stress to the HT22 cells. The oxidative stress suppressed the cell viability and decreased the levels of lactate dehydrogenase (LDH), superoxide dismutase (SOD), mitochondria membrane potential (MMP) and Glutathione peroxidase (GSH-Px). It up-regulated malondialdehyde (MDA) production and intracellular reactive oxygen species (ROS). In addition, phosphoinositide 3 kinase/protein kinase B/Glycogen synthase kinase3β (PI3K/Akt/GSK3β) and mitogen activated protein kinase (MAPK) were also involved in this process. We found that pre-treatment with quercetin can inhibited OA-induced the hyperphosphorylation of tau protein and oxidative stress. Moreover, pre-treatment with quercetin not only inhibited OA-induced apoptosis via the reduction of Bax, and up-regulation of cleaved caspase 3, but also via the inhibition of PI3K/Akt/GSK3β, MAPKs and activation of NF-κB p65. Our findings suggest the therapeutic potential of quercetin to treat AD. PMID:27050422

  14. Antioxidant study of quercetin and their metal complex and determination of stability constant by spectrophotometry method.

    PubMed

    Ravichandran, R; Rajendran, M; Devapiriam, D

    2014-03-01

    Quercetin found chelate cadmium ions, scavenge free radicals produced by cadmium. Hence new complex, quercetin with cadmium was synthesised, and the synthesised complex structures were determined by UV-vis spectrophotometry, infrared spectroscopy, thermogravimetry and differential thermal analysis techniques (UV-vis, IR, TGA and DTA). The equilibrium stability constants of quercetin-cadmium complex were determined by Job's method. The determined stability constant value of quercetin-cadminum complex at pH 4.4 is 2.27×10(6) and at pH 7.4 is 7.80×10(6). It was found that the quercetin and cadmium ion form 1:1 complex in both pH 4.4 and pH 7.4. The structure of the compounds was elucidated on the basis of obtained results. Furthermore, the antioxidant activity of the free quercetin and quercetin-cadmium complexes were determined by DPPH and ABTS assays.

  15. Potentiation of luteolin cytotoxicity by flavonols fisetin and quercetin in human chronic lymphocytic leukemia cell lines.

    PubMed

    Sak, Katrin; Kasemaa, Kristi; Everaus, Hele

    2016-09-14

    Despite numerous studies chronic lymphocytic leukemia (CLL) still remains an incurable disease. Therefore, all new compounds and novel strategies which are able to eradicate CLL cells should be considered as valuable clues for a potential future remedy against this malignancy. In the present study, the cytotoxic profiles of natural flavonoids were described in two human CLL cell lines, HG-3 and EHEB, indicating the flavone luteolin as the most potent flavonoid with half-maximal inhibitory constants (IC50) of 37 μM and 26 μM, respectively. Luteolin significantly increased the apoptotic cell population in both cell lines by increasing the activities of caspases-3 and -9 and triggering the intrinsic apoptotic pathway. Two flavonols, fisetin and quercetin, were somewhat less efficient in suppressing cellular viability, whereas baicalein, chrysin, (+)-catechin and hesperetin exerted only a small or no response at doses as high as 100 μM. Both fisetin and quercetin were able to augment the cytotoxic activity of luteolin in both cell lines by reducing the IC50 values up to four fold. As a result of this, luteolin displayed cytotoxicity activity already at low micromolar concentrations that could potentially be physiologically achievable through oral ingestion. No other tested flavonoids were capable of sensitizing CLL cells to luteolin pointing to a specific binding of fisetin and quercetin to the cellular targets which interfere with the signaling pathways induced by luteolin. Although further molecular studies to unravel this potentiating mechanism are certainly needed, this phenomenon could contribute to future remedies for prevention and treatment of chronic lymphocytic leukemia.

  16. Potentiation of luteolin cytotoxicity by flavonols fisetin and quercetin in human chronic lymphocytic leukemia cell lines.

    PubMed

    Sak, Katrin; Kasemaa, Kristi; Everaus, Hele

    2016-09-14

    Despite numerous studies chronic lymphocytic leukemia (CLL) still remains an incurable disease. Therefore, all new compounds and novel strategies which are able to eradicate CLL cells should be considered as valuable clues for a potential future remedy against this malignancy. In the present study, the cytotoxic profiles of natural flavonoids were described in two human CLL cell lines, HG-3 and EHEB, indicating the flavone luteolin as the most potent flavonoid with half-maximal inhibitory constants (IC50) of 37 μM and 26 μM, respectively. Luteolin significantly increased the apoptotic cell population in both cell lines by increasing the activities of caspases-3 and -9 and triggering the intrinsic apoptotic pathway. Two flavonols, fisetin and quercetin, were somewhat less efficient in suppressing cellular viability, whereas baicalein, chrysin, (+)-catechin and hesperetin exerted only a small or no response at doses as high as 100 μM. Both fisetin and quercetin were able to augment the cytotoxic activity of luteolin in both cell lines by reducing the IC50 values up to four fold. As a result of this, luteolin displayed cytotoxicity activity already at low micromolar concentrations that could potentially be physiologically achievable through oral ingestion. No other tested flavonoids were capable of sensitizing CLL cells to luteolin pointing to a specific binding of fisetin and quercetin to the cellular targets which interfere with the signaling pathways induced by luteolin. Although further molecular studies to unravel this potentiating mechanism are certainly needed, this phenomenon could contribute to future remedies for prevention and treatment of chronic lymphocytic leukemia. PMID:27489195

  17. Mechanisms underlying the protective effects of myricetin and quercetin following oxygen/glucose deprivation-induced cell swelling and the reduction in glutamate uptake in glial cells

    Technology Transfer Automated Retrieval System (TEKTRAN)

    C6 glial cells were exposed to oxygen-glucose deprivation (OGD) in cell culture for 5 hr and cell swelling was determined 90 min after the end of OGD. The OGD-induced increase in swelling was significantly blocked by the two flavonoids studied, quercetin and myricetin. The OGD-induced increase in ...

  18. Silencing of Hsp27 and Hsp72 in glioma cells as a tool for programmed cell death induction upon temozolomide and quercetin treatment

    SciTech Connect

    Jakubowicz-Gil, Joanna; Langner, Ewa; Bądziul, Dorota; Wertel, Iwona; Rzeski, Wojciech

    2013-12-15

    The aim of the present study was to investigate whether silencing of Hsp27 or Hsp72 expression in glioblastoma multiforme T98G and anaplastic astrocytoma MOGGCCM cells increases their sensitivity to programmed cell death induction upon temozolomide and/or quercetin treatment. Transfection with specific siRNA was performed for the Hsp gene silencing. As revealed by microscopic observation and flow cytometry, the inhibition of Hsp expression was correlated with severe apoptosis induction upon the drug treatment studied. No signs of autophagy were detected. This was correlated with a decreased mitochondrial membrane potential, increased level of cytochrome c in the cytoplasm, and activation of caspase 3 and caspase 9. All these results suggest that the apoptotic signal was mediated by an internal pathway. Additionally, in a large percentage of cells treated with temozolomide, with or without quercetin, granules within the ER system were found, which was accompanied by an increased level of caspase 12 expression. This might be correlated with ER stress. Quercetin and temozolomide also changed the shape of nuclei from circular to “croissant like” in both transfected cell lines. Our results indicate that blocking of Hsp27 and Hsp72 expression makes T98G cells and MOGGCCM cells extremely vulnerable to apoptosis induction upon temozolomide and quercetin treatment and that programmed cell death is initiated by an internal signal. - Highlights: • Hsps gene silencing induced severe apoptosis upon temozolomide–quercetin treatment • Apoptosis in transfected glioma cells was initiated by internal signal • Programmed cell death was preceded by ER stress • Temozolomide–quercetin treatment changed nuclei shape in transfected glioma cells.

  19. Inhibition of gastrointestinal release of acetylcholine by quercetin as a possible mode of action of Psidium guajava leaf extracts in the treatment of acute diarrhoeal disease.

    PubMed

    Lutterodt, G D

    1989-05-01

    The electrically stimulated guinea-pig ileum and spontaneously contracting guinea-pig ileum preparations were employed in studies on the effects of an alcoholic extract and two flavonoid compounds, quercetin and quercetin-3-arabinoside, extracted from the leaves of Psidium guajava. The extract showed a morphine-like inhibition of acetylcholine release in the coaxially stimulated ileum, together with an initial increase in muscular tone, followed by a gradual decrease. The morphine-like inhibition was found to be due to quercetin, starting at concentrations of 1.6 micrograms/ml. The glycoside did not show any such action at concentrations of up to 1.28 mg/ml. The extract inhibited spontaneous contractions in the unstimulated ileum with a concentration-response relationship.

  20. Effect of ocean mixing on the transient climate response to a CO/sub 2/ increase: analysis of recent model results

    SciTech Connect

    Harvey, L.D.D.

    1986-02-20

    Results of several recent reports on the role of ocean mixing in the transient response to a CO/sub 2/ doubling are analyzed and compared. Wigley and Schlesinger (1985) obtained an analytical solution to a one-dimensional box-diffusion (BD) ocean model in which the mixed layer e-folding time tau/sub e/ varies as f/sub 0/ /sup 2/KdeltaT/sub eq//sup 2/, where f/sub 0/ is the planetary ocean fraction, K is the ocean diffusivity, and deltaT/sub eq/ is the equilibrium temperature response. The dependence of tau/sub e/ obtained by Wigley and Schlesinger is compared with that obtained using simple land-seas resolved and box-advection-diffusion (BAD) models. For a BAD model the dependence of tau/sub e/ on both K and ..delta..T/sub eq/ is significantly less than for a BD model. A comparison of the transient response of BD and BAD models using the same effective K indicates that the behavior of the BAD model cannot be captured using a BD model, except during the first few decades of the transient response. Schlesinger et al. (1985) estimated atmospheric and mixed layer values of tau/sub e/ for their coupled atmosphere-ocean general circulation model (A/O GCM) by fitting a BD model to the first 16 years of their A/O GCM transient response and then integrating the BD model for 200 years. However, Schlesinger et al. appear to have overestimated values of tau/sub e/ for their long-term A/O GCM by fitting their short-term A/O GCM transient response to a model in which the equilibrium globally averaged atmospheric and mixed layer temperature responses are equal, whereas this is apparently not true for their A/O GCM. Hansen et al. (1984) estimated tau/sub e/ by modeling three-dimensional ocean mixing as a series of isolated BD models, one below each horizontal grid point, and by using tritium-based diffusion coefficients, which probably are too large when applied to heat and probably lead to an overestimate of the actual tau.

  1. Quercetin represses apolipoprotein B expression by inhibiting the transcriptional activity of C/EBPβ.

    PubMed

    Shimizu, Makoto; Li, Juan; Inoue, Jun; Sato, Ryuichiro

    2015-01-01

    Quercetin is one of the most abundant polyphenolic flavonoids found in fruits and vegetables and has anti-oxidative and anti-obesity effects. Because the small intestine is a major absorptive organ of dietary nutrients, it is likely that highly concentrated food constituents, including polyphenols, are present in the small intestinal epithelial cells, suggesting that food factors may have a profound effect in this tissue. To identify novel targets of quercetin in the intestinal enterocytes, mRNA profiling using human intestinal epithelial Caco-2 cells was performed. We found that mRNA levels of some apolipoproteins, particularly apolipoprotein B (apoB), are downregulated in the presence of quercetin. On the exposure of Caco-2 cells to quercetin, both mRNA and protein levels of apoB were decreased. Promoter analysis of the human apoB revealed that quercetin response element is localized at the 5'-proximal promoter region, which contains a conserved CCAAT enhancer-binding protein (C/EBP)-response element. We found that quercetin reduces the promoter activity of apoB, driven by the enforced expression of C/EBPβ. Quercetin had no effect on either mRNA or protein levels of C/EBPβ. In contrast, we found that quercetin inhibits the transcriptional activity of C/EBPβ but not its recruitment to the apoB promoter. On the exposure of Caco-2 cells to quercetin 3-O-glucuronide, which is in a cell-impermeable form, no notable change in apoB mRNA was observed, suggesting an intracellular action of quercetin. In vitro interaction experiments using quercetin-conjugated beads revealed that quercetin binds to C/EBPβ. Our results describe a novel regulatory mechanism of transcription of apolipoprotein genes by quercetin in the intestinal enterocytes. PMID:25875015

  2. New benzophenone and quercetin galloyl glycosides from Psidium guajava L.

    PubMed

    Matsuzaki, Keiichi; Ishii, Rie; Kobiyama, Kaori; Kitanaka, Susumu

    2010-07-01

    New benzophenone and flavonol galloyl glycosides were isolated from an 80% MeOH extract of Psidium guajava L. (Myrtaceae) together with five known quercetin glycosides. The structures of the novel glycosides were elucidated to be 2,4,6-trihydroxybenzophenone 4-O-(6''-O-galloyl)-beta-D: -glucopyranoside (1, guavinoside A), 2,4,6-trihydroxy-3,5-dimethylbenzophenone 4-O-(6''-O-galloyl)-beta-D: -glucopyranoside (2, guavinoside B), and quercetin 3-O-(5''-O-galloyl)-alpha-L: -arabinofuranoside (3, guavinoside C) by NMR, MS, UV, and IR spectroscopies. Isolated phenolic glycosides showed significant inhibitory activities against histamine release from rat peritoneal mast cells, and nitric oxide production from a murine macrophage-like cell line, RAW 264.7.

  3. Effect of Quercetin on lipid peroxidation and changes in lung morphology in experimental influenza virus infection.

    PubMed

    Kumar, Pankaj; Sharma, Sonal; Khanna, MadhU; Raj, Hanumantharao Guru

    2003-06-01

    Influenza virus infection, induced experimentally in mice, was associated with marked changes in lung morphology viz. epithelial damage with focal areas of reactive papillary hyperplasia, infiltration of leukocytes and development of oxidative stress, as evidenced by increased superoxide radical production and lipid peroxidation (LPO) products by alveolar macrophages. These effects were observed on the 5th day after virus instillation. The levels of superoxide and LPO were measured spectrophotometrically by the nitroblue tetrazolium (NBT) assay and thiobarbituric acid reactive species (TBARS) assay, respectively. The former increased by 1.5-2 fold and the latter was raised by 85% when compared with normal control. Supplementation of intranasal viral instillation with the anti-oxidant, Quercetin, given orally, resulted in a significant decrease in the levels of both superoxide radicals and LPO products. There was also a significant decrease in the number of infiltrating cells. A mild to moderate protective effect was observed in lung morphology. Thus, Quercetin may be useful as a drug in reducing the oxidative stress induced by influenza virus infection in the lung, and protect it from the toxic effects of the free radicals.

  4. Effects of the plant flavonoids silymarin and quercetin on arsenite-induced oxidative stress in CHO-K1 cells.

    PubMed

    Bongiovanni, G A; Soria, E A; Eynard, A R

    2007-06-01

    Chronic toxic effects of arsenic resulting from drinking water are a human health problem, especially in South-America and Asia. Arsenic is capable of influencing various cellular processes, causing adverse effects, including cancer. Although the exact mechanism of the action is not known, a correlation between oxidative stress, tumour promotion and arsenic exposure has been observed. We examined the effects of silymarin and quercetin, in counteracting oxidative stress produced by acute or sub-chronic sodium arsenite exposure. The stress responses to arsenite included an increase in the heat shock protein 70 kDa expression, lipid peroxidation assayed by conjugated dienes measure, and gamma-glutamyl-transpeptidase activity. We found that all these stress responses were eliminated by silymarin and quercetin in acute experiments. Both flavonoids diminished the conjugated dienes formation during sub-chronic cultures. Our results suggest that these antioxidant flavonoids, which may be easily incorporated into the diet, may afford a protective effect against arsenite-induced cytotoxicity.

  5. Polychlorinated biphenyls impair blood-brain barrier integrity via disruption of tight junction proteins in cerebrum, cerebellum and hippocampus of female Wistar rats: neuropotential role of quercetin.

    PubMed

    Selvakumar, K; Prabha, R Lakshmi; Saranya, K; Bavithra, S; Krishnamoorthy, G; Arunakaran, J

    2013-07-01

    Polychlorinated biphenyls (PCBs) comprise a ubiquitous class of toxic substances associated with carcinogenic and tumor-promoting effects as well as neurotoxic properties. Reactive oxygen species, which is produced from PCBs, alters blood-brain barrier (BBB) integrity, which is paralleled by cytoskeletal rearrangements and redistribution and disappearance of tight junction proteins (TJPs) like claudin-5 and occludin. Quercetin, a potent antioxidant present in onion and other vegetables, appears to protect brain cells against oxidative stress, a tissue-damaging process associated with Alzheimer's and other neurodegenerative disorders. The aim of this study is to analyze the role of quercetin on oxidative stress markers and transcription of transmembrane and cytoplasmic accessory TJPs on cerebrum, cerebellum and hippocampus of female rats exposed to PCBs. Rats were divided into the following four groups. Group I: received only vehicle (corn oil) intraperitoneally (i.p.); group II: received Aroclor 1254 at a dose of 2 mg/kg body weight (bwt)/day (i.p); group III: received Aroclor 1254 (i.p.) and simultaneously quercetin 50 mg/kg bwt/day through gavage and group IV: received quercetin alone gavage. From the experiment, the levels of hydrogen peroxide, lipid peroxidation and thiobarbituric acid reactive substances were observed to increase significantly in cerebrum, cerebellum and hippocampus as 50%, 25% and 20%, respectively, after exposure to PCB, and the messenger RNA expression of TJP in rats exposed to PCBs is decreased and is retrieved to the normal level simultaneously in quercetin-treated rats. Hence, quercetin can be used as a preventive medicine to PCBs exposure and prevents neurodegenerative disorders.

  6. Transient increases in cytosolic free calcium appear to be required for the migration of adherent human neutrophils [published erratum appears in J Cell Biol 1990 Mar;110(3):861

    PubMed Central

    1990-01-01

    Human neutrophils exhibit multiple increases in cytosolic free calcium concentration [( Ca2+]i) spontaneously and in response to the chemoattractant N-formyl-L-methionyl-L-leucyl-L-phenylalanine (Jaconi, M. E. E., R. W. Rivest, W. Schlegel, C. B. Wollheim, D. Pittet, and P. D. Lew. 1988. J. Biol. Chem. 263:10557-10560). The function of these repetitive increases in [Ca2+]i, as well as the role of Ca2+ in human neutrophil migration, remain unresolved. We have used microspectrofluorometry to measure [Ca2+]i in single fura-2-loaded human neutrophils as they moved on poly-D-lysine-coated glass in the presence of serum. To investigate the role of Ca2+ in human neutrophil migration, we examined cells in the presence and absence of extracellular Ca2+, as well as intracellular Ca2(+)-buffered and Ca2(+)- depleted cells. In the presence of extracellular Ca2+, multiple increases and decreases in [Ca2+]i were frequently observed, and at least one such transient increase in [Ca2+]i occurred in every moving cell during chemokinesis, chemotaxis, and phagocytosis. In addition, neutrophils that extended pseudopodia and assumed a polarized morphology after plating onto a surface were always observed to exhibit [Ca2+]i transients even in the absence of chemoattractant. In contrast, a [Ca2+]i transient was observed in only one of the nonpolarized stationary cells that were examined (n = 15). Although some cells exhibited relatively periodic increases and decreases in [Ca2+]i, resembling the regular oscillations that have been observed in some cell types, many others exhibited increases and decreases in [Ca2+]i that varied in their timing, magnitude, and duration. Buffering of [Ca2+]i or removal of extracellular Ca2+ damped out or blocked transient increases in [Ca2+]i and reduced or inhibited the migration of neutrophils. Under these conditions, polarized cells were often observed to make repeated attempts at migration, but they remained anchored at their rear. These data suggest

  7. Effect of pioglitazone, quercetin and hydroxy citric acid on extracellular matrix components in experimentally induced non-alcoholic steatohepatitis

    PubMed Central

    Mohan, Surapaneni Krishna; Veeraraghavan, Vishnu Priya; Jainu, Mallika

    2015-01-01

    Objective(s): Non-alcoholic steatohepatitis (NASH), is an important component of Non-alcoholic fatty liver disease (NAFLD) spectrum, which progresses to the end stage liver disease, if not diagnosed and treated properly. The disproportionate production of pro- and anti-inflammatory adipokines secreted from fat contributes to the pathogenesis of NASH. In this study, the comparative effect of pioglitazone, quercetin and hydroxy citric acid on extracellular matrix (ECM) component levels were studied in experimentally induced NASH. Materials and Methods: The experimental protocol consists of using 48 male Wister rats, which were divided into 8 groups. The levels of hyaluronic acid, leptin and adiponectin were monitored in experimental NASH. Results: The experimental NASH rats treated with pioglitazone showed significant decrease in the levels of hyaluronic acid and significant increase in adiponectin levels when compared to experimentally induced NASH group, but did not show any effect on the levels of leptin. Contrary to these two drugs, viz. pioglitazone and hydroxy citric acid, the group treated with quercetin showed significant decrease in the levels of hyaluronic acid and leptin and significant decrease in adiponectin levels compared with that of experimentally induced NASH NASH group, offering maximum protection against NASH. Conclusion: Considering our findings, it could be concluded that quercetin may offer maximum protection against NASH by significantly increasing the levels of adiponectin, when compared to pioglitazone and hydroxy citric acid. PMID:26557974

  8. PI-103 and Quercetin Attenuate PI3K-AKT Signaling Pathway in T- Cell Lymphoma Exposed to Hydrogen Peroxide.

    PubMed

    Maurya, Akhilendra Kumar; Vinayak, Manjula

    2016-01-01

    Phosphatidylinositol 3 kinase-protein kinase B (PI3K-AKT) pathway has been considered as major drug target site due to its frequent activation in cancer. AKT regulates the activity of various targets to promote tumorigenesis and metastasis. Accumulation of reactive oxygen species (ROS) has been linked to oxidative stress and regulation of signaling pathways for metabolic adaptation of tumor microenvironment. Hydrogen peroxide (H2O2) in this context is used as ROS source for oxidative stress preconditioning. Antioxidants are commonly considered to be beneficial to reduce detrimental effects of ROS and are recommended as dietary supplements. Quercetin, a ubiquitous bioactive flavonoid is a dietary component which has attracted much of interest due to its potential health-promoting effects. Present study is aimed to analyze PI3K-AKT signaling pathway in H2O2 exposed Dalton's lymphoma ascite (DLA) cells. Further, regulation of PI3K-AKT pathway by quercetin as well as PI-103, an inhibitor of PI3K was analyzed. Exposure of H2O2 (1mM H2O2 for 30min) to DLA cells caused ROS accumulation and resulted in increased phosphorylation of PI3K and downstream proteins PDK1 and AKT (Ser-473 and Thr-308), cell survival factors BAD and ERK1/2, as well as TNFR1. However, level of tumor suppressor PTEN was declined. Both PI-103 & quercetin suppressed the enhanced level of ROS and significantly down-regulated phosphorylation of AKT, PDK1, BAD and level of TNFR1 as well as increased the level of PTEN in H2O2 induced lymphoma cells. The overall result suggests that quercetin and PI3K inhibitor PI-103 attenuate PI3K-AKT pathway in a similar mechanism. PMID:27494022

  9. PI-103 and Quercetin Attenuate PI3K-AKT Signaling Pathway in T- Cell Lymphoma Exposed to Hydrogen Peroxide

    PubMed Central

    Maurya, Akhilendra Kumar; Vinayak, Manjula

    2016-01-01

    Phosphatidylinositol 3 kinase—protein kinase B (PI3K-AKT) pathway has been considered as major drug target site due to its frequent activation in cancer. AKT regulates the activity of various targets to promote tumorigenesis and metastasis. Accumulation of reactive oxygen species (ROS) has been linked to oxidative stress and regulation of signaling pathways for metabolic adaptation of tumor microenvironment. Hydrogen peroxide (H2O2) in this context is used as ROS source for oxidative stress preconditioning. Antioxidants are commonly considered to be beneficial to reduce detrimental effects of ROS and are recommended as dietary supplements. Quercetin, a ubiquitous bioactive flavonoid is a dietary component which has attracted much of interest due to its potential health-promoting effects. Present study is aimed to analyze PI3K-AKT signaling pathway in H2O2 exposed Dalton’s lymphoma ascite (DLA) cells. Further, regulation of PI3K-AKT pathway by quercetin as well as PI-103, an inhibitor of PI3K was analyzed. Exposure of H2O2 (1mM H2O2 for 30min) to DLA cells caused ROS accumulation and resulted in increased phosphorylation of PI3K and downstream proteins PDK1 and AKT (Ser-473 and Thr-308), cell survival factors BAD and ERK1/2, as well as TNFR1. However, level of tumor suppressor PTEN was declined. Both PI-103 & quercetin suppressed the enhanced level of ROS and significantly down-regulated phosphorylation of AKT, PDK1, BAD and level of TNFR1 as well as increased the level of PTEN in H2O2 induced lymphoma cells. The overall result suggests that quercetin and PI3K inhibitor PI-103 attenuate PI3K-AKT pathway in a similar mechanism. PMID:27494022

  10. Different profiles of quercetin metabolites in rat plasma: comparison of two administration methods.

    PubMed

    Kawai, Yoshichika; Saito, Satomi; Nishikawa, Tomomi; Ishisaka, Akari; Murota, Kaeko; Terao, Junji

    2009-03-23

    The bioavailability of polyphenols in human and rodents has been discussed regarding their biological activity. We found different metabolite profiles of quercetin in rat plasma between two administration procedures. A single intragastric administration (50 mg/kg) resulted in the appearance of a variety of metabolites in the plasma, whereas only a major fraction was detected by free access (1% quercetin). The methylated/non-methylated metabolites ratio was much higher in the free access group. Mass spectrometric analyses showed that the fraction from free access contained highly conjugated quercetin metabolites such as sulfo-glucuronides of quercetin and methylquercetin. The metabolite profile of human plasma after an intake of onion was similar to that with intragastric administration in rats. In vitro oxidation of human low-density lipoprotein showed that methylation of the catechol moiety of quercetin significantly attenuated the antioxidative activity. These results might provide information about the bioavailability of quercetin when conducting animal experiments. PMID:19270373

  11. Different profiles of quercetin metabolites in rat plasma: comparison of two administration methods.

    PubMed

    Kawai, Yoshichika; Saito, Satomi; Nishikawa, Tomomi; Ishisaka, Akari; Murota, Kaeko; Terao, Junji

    2009-03-23

    The bioavailability of polyphenols in human and rodents has been discussed regarding their biological activity. We found different metabolite profiles of quercetin in rat plasma between two administration procedures. A single intragastric administration (50 mg/kg) resulted in the appearance of a variety of metabolites in the plasma, whereas only a major fraction was detected by free access (1% quercetin). The methylated/non-methylated metabolites ratio was much higher in the free access group. Mass spectrometric analyses showed that the fraction from free access contained highly conjugated quercetin metabolites such as sulfo-glucuronides of quercetin and methylquercetin. The metabolite profile of human plasma after an intake of onion was similar to that with intragastric administration in rats. In vitro oxidation of human low-density lipoprotein showed that methylation of the catechol moiety of quercetin significantly attenuated the antioxidative activity. These results might provide information about the bioavailability of quercetin when conducting animal experiments.

  12. Nanoparticle Based Delivery of Quercetin for the Treatment of Carbon Tetrachloride Mediated Liver Cirrhosis in Rats.

    PubMed

    Verma, Shashi Kant; Rastogil, Shweta; Arora, Indu; Javed, Kalim; Akhtar, Mohd; Samim, Mohd

    2016-02-01

    Liver fibrosis is the common response to chronic liver injury and ultimately leads to cirrhosis. There is a pressing need in the pharmaceutical industry to develop efficient well-targeted drug delivery systems, which are lacking to date. This study was designed to investigate the efficacy of a nanoquercetin NQ; i.e., quercetin encapsulated in PAG (p-aminophenyl-1-thio-β-D-galactopryranoside)-coated NIPAAM (N-isopropyl acrylamide) nanopolymer in liver compared with naked quercetin (Q) using a carbon tetrachloride (CCl₄)-mediated liver cirrhosis model. NQ was more effective at restoring liver membrane integrity as indicated by significantly reduced serum markers, including Alanine Transaminase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) and Lactate Dehydrogenase (LDH), compared with naked Q. The findings of reduced collagen and histopathology also show that the NQ effects were much better than those of naked Q. Biochemical parameters, including antioxidant defense enzymes, also provide supporting evidence. Furthermore, the decrease in NF-κB and NOS-2 expression in the NQ-treated groups was also much stronger than in the naked Q-treated group. Thus, the data clearly suggest that NQ not only provides significant hepatoprotection compared with naked Q, but it also substantially lowered the required concentration (1,000 to 10,000-fold lower) by increasing the bioavailability. PMID:27305761

  13. Nanoparticle Based Delivery of Quercetin for the Treatment of Carbon Tetrachloride Mediated Liver Cirrhosis in Rats.

    PubMed

    Verma, Shashi Kant; Rastogil, Shweta; Arora, Indu; Javed, Kalim; Akhtar, Mohd; Samim, Mohd

    2016-02-01

    Liver fibrosis is the common response to chronic liver injury and ultimately leads to cirrhosis. There is a pressing need in the pharmaceutical industry to develop efficient well-targeted drug delivery systems, which are lacking to date. This study was designed to investigate the efficacy of a nanoquercetin NQ; i.e., quercetin encapsulated in PAG (p-aminophenyl-1-thio-β-D-galactopryranoside)-coated NIPAAM (N-isopropyl acrylamide) nanopolymer in liver compared with naked quercetin (Q) using a carbon tetrachloride (CCl₄)-mediated liver cirrhosis model. NQ was more effective at restoring liver membrane integrity as indicated by significantly reduced serum markers, including Alanine Transaminase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) and Lactate Dehydrogenase (LDH), compared with naked Q. The findings of reduced collagen and histopathology also show that the NQ effects were much better than those of naked Q. Biochemical parameters, including antioxidant defense enzymes, also provide supporting evidence. Furthermore, the decrease in NF-κB and NOS-2 expression in the NQ-treated groups was also much stronger than in the naked Q-treated group. Thus, the data clearly suggest that NQ not only provides significant hepatoprotection compared with naked Q, but it also substantially lowered the required concentration (1,000 to 10,000-fold lower) by increasing the bioavailability.

  14. Oxidative stress and brain mitochondria swelling induced by endosulfan and protective role of quercetin in rat.

    PubMed

    Lakroun, Zhoura; Kebieche, Mohamed; Lahouel, Asma; Zama, Djamila; Desor, Frederique; Soulimani, Rachid

    2015-05-01

    The neurological damages resulted by endosulfan poisoning is not completely elucidated, especially in cellular organelles such as mitochondria. In the present study, the pro-oxidant effect of endosulfan on brain mitochondria was first investigated. Gavages of endosulfan into rats at the dose of 2 mg/kg induced oxidative stress in this organelle since it provokes a significant reduction of catalase (CAT), superoxide dismutase (SOD), and glutathione (GSH) level. In addition, a significant increase in mitochondria swelling and malondialdehyde (MDA) levels were observed in neuronal mitochondria, indicating clearly an intense peroxidation within mitochondria. Second, the protective effect of quercetin (QE) (10 mg/kg) against endosulfan-induced oxidative stress in mitochondria was also assessed. Indeed, the pretreatment of rats with QE protects brain mitochondria from oxidative stress, lipid peroxidation, and mitochondria swelling induced by endosulfan. The activities of antioxidant enzymes and the mitochondrial content of GSH and MDA were returned to control values. Thus, although endosulfan can have neurotoxic effects in brain rats, this toxicity can be prevented by quercetin.

  15. Quercetin from shallots (Allium cepa L. var. aggregatum) is more bioavailable than its glucosides.

    PubMed

    Wiczkowski, Wieslaw; Romaszko, Jerzy; Bucinski, Adam; Szawara-Nowak, Dorota; Honke, Joanna; Zielinski, Henryk; Piskula, Mariusz K

    2008-05-01

    The lipophilic character of quercetin suggests that it can cross enterocyte membranes via simple diffusion. Therefore, it should be more bioavailable than its glucosides, which require preliminary hydrolysis or active transport for absorption. However, the published human studies show that quercetin is less bioavailable than its glucosides. Assuming that low bioavailability of quercetin aglycone provided to humans as a pure substance is the result of its low solubility in the digestive tract, we studied its bioavailability from dietary sources in which quercetin was dispersed in the food matrix. In a randomized crossover study, 9 volunteers took a single dose of either shallot flesh (99.2% quercetin glucosides and 0.8% quercetin aglycone) or dry shallot skin (83.3% quercetin aglycone and 16.7% quercetin glucosides), providing 1.4 mg quercetin per kg of body weight. Blood samples were collected before and after consumption of shallot preparations. Plasma quercetin was measured on HPLC with electrochemical detection after plasma enzymatic treatment. The maximum plasma quercetin concentration of 1.02 +/- 0.13 micromol/L was reached at 2.33 +/- 0.50 h after shallot flesh consumption compared with 3.95 +/- 0.62 micromol/L at 2.78 +/- 0.15 h after dry skin consumption. The area under the concentration-time curve after dry skin consumption was 47.23 +/- 7.53 micromol x h(-1) x L(-1) and was significantly higher than that after shallot flesh intake (22.23 +/- 2.32 micromol x h(-1) x L(-1)). When provided along with dietary sources, quercetin aglycone is more bioavailable than its glucosides in humans. Results point to the food matrix as a key factor.

  16. Quercetin from shallots (Allium cepa L. var. aggregatum) is more bioavailable than its glucosides.

    PubMed

    Wiczkowski, Wieslaw; Romaszko, Jerzy; Bucinski, Adam; Szawara-Nowak, Dorota; Honke, Joanna; Zielinski, Henryk; Piskula, Mariusz K

    2008-05-01

    The lipophilic character of quercetin suggests that it can cross enterocyte membranes via simple diffusion. Therefore, it should be more bioavailable than its glucosides, which require preliminary hydrolysis or active transport for absorption. However, the published human studies show that quercetin is less bioavailable than its glucosides. Assuming that low bioavailability of quercetin aglycone provided to humans as a pure substance is the result of its low solubility in the digestive tract, we studied its bioavailability from dietary sources in which quercetin was dispersed in the food matrix. In a randomized crossover study, 9 volunteers took a single dose of either shallot flesh (99.2% quercetin glucosides and 0.8% quercetin aglycone) or dry shallot skin (83.3% quercetin aglycone and 16.7% quercetin glucosides), providing 1.4 mg quercetin per kg of body weight. Blood samples were collected before and after consumption of shallot preparations. Plasma quercetin was measured on HPLC with electrochemical detection after plasma enzymatic treatment. The maximum plasma quercetin concentration of 1.02 +/- 0.13 micromol/L was reached at 2.33 +/- 0.50 h after shallot flesh consumption compared with 3.95 +/- 0.62 micromol/L at 2.78 +/- 0.15 h after dry skin consumption. The area under the concentration-time curve after dry skin consumption was 47.23 +/- 7.53 micromol x h(-1) x L(-1) and was significantly higher than that after shallot flesh intake (22.23 +/- 2.32 micromol x h(-1) x L(-1)). When provided along with dietary sources, quercetin aglycone is more bioavailable than its glucosides in humans. Results point to the food matrix as a key factor. PMID:18424596

  17. Quercetin suppresses HeLa cells by blocking PI3K/Akt pathway.

    PubMed

    Xiang, Tao; Fang, Yong; Wang, Shi-Xuan

    2014-10-01

    To explore the effect of quercetin on the proliferation and apoptosis of HeLa cells, HeLa cells were incubated with quercetin at different concentrations. Cell viability was evaluated by MTT assay, cell apoptosis was detected by Annexin-V/PI double labeled cytometry and DNA ladder assay. Cell cycle was flow cytometrically determined and the morphological changes of the cells were observed under a fluorescence microscope after Hoechst 33258 staining and the apoptosis-related proteins in the HeLa cells were assessed by Western blotting. The results showed that quercetin significantly inhibited the growth of HeLa cells and induced obvious apoptosis in vitro in a time- and dose-dependent manner. Moreover, quercetin induced apoptosis of HeLa cells in cell cycle-dependent manner because quercetin could induce arrest of HeLa cells at G0/G1 phase. Quercetin treatment down-regulated the expression of the PI3K and p-Akt. In addition, quercetin could down-regulate expression of bcl-2, up-regulate Bax, but exerted no effect on the overall expression of Akt. We are led to conclude that quercetin induces apoptosis via PI3k/Akt pathways, and quercetin has potential to be used as an anti-tumor agent against human cervix cancer.

  18. Human myeloperoxidase activity is inhibited in vitro by quercetin. Comparison with three related compounds.

    PubMed

    Pincemail, J; Deby, C; Thirion, A; de Bruyn-Dister, M; Goutier, R

    1988-05-15

    Quercetin is an effective inhibitor of human myeloperoxidase (MPO) activity, both with purified enzyme (IC50 = 3.5 microM) and in a system using stimulated human neutrophils. Quercetin is significantly more potent than three other related compounds (rutin, rutin sulfate and troxerutin) and than methimazole, a previously-known myeloperoxidase inhibitor. The inhibitory activity of quercetin is of the competitive type. Moreover, quercetin is directly able to scavenge hypochlorous acid (HOCl), a chlorinated species generated by the MPO/H2O2/Cl- system.

  19. Effects of Functional Groups and Sugar Composition of Quercetin Derivatives on Their Radical Scavenging Properties.

    PubMed

    Kato, Komei; Ninomiya, Masayuki; Tanaka, Kaori; Koketsu, Mamoru

    2016-07-22

    Quercetin derivatives are widespread in the plant kingdom and exhibit various biological actions. The aim of this study was to investigate the structure-activity relationships of quercetin derivatives, with a focus on the influence of functional groups and sugar composition on their antioxidant capacity. A series of quercetin derivatives were therefore prepared and assessed for their DPPH radical scavenging properties. Isoquercetin O-gallates were more potent radical scavengers than quercetin. The systematic analysis highlights the importance of the distribution of hydroxy substituents in isoquercetin O-gallates to their potency. PMID:27314621

  20. Oral co-administration of α-lipoic acid, quercetin and captopril prevents gallium arsenide toxicity in rats.

    PubMed

    Bhatt, Kapil; Flora, S J S

    2009-07-01

    Gallium arsenide (GaAs), an inter-metallic semiconductor, known to exhibit superior optical and electronic properties compared to silicon, promotes its use in semiconductor industries. Extensive use of GaAs will inevitably lead to an increase in the exposure of workers manufacturing these products. Antioxidants are exogenous or endogenous compounds acting in several ways, including scavenging reactive oxygen species (ROS) or their precursors, inhibiting ROS formation, and binding metal ions needed for the catalysis of ROS generation. In the present study we investigated the protective efficacy of α-lipoic acid, quercetin and captopril individually against gallium arsenide exposure. Co-administration of α-lipoic acid with GaAs was most effective in reducing GaAs induced inhibition of blood δ-aminolevulinic acid dehydratase (ALAD) activity, liver, kidney and brain reduced glutathione (GSH) level and elevation of oxidized glutathione (GSSG). Captopril, on the other hand was effective in reducing thiobarbituric acid reactive substance (TBARS) levels, while quercetin reduced ROS in liver and kidney. The results suggest comparatively better preventive efficacy of concomitant α-lipoic acid administration during Gallium arsenide exposure compared to quercetin and captopril in preventing GaAs induced oxidative stress.

  1. Quercetin-loaded freeze-dried nanomicelles: Improving absorption and anti-glioma efficiency in vitro and in vivo.

    PubMed

    Wang, Gang; Wang, Jun-Jie; Chen, Xuan-Li; Du, Li; Li, Fei

    2016-08-10

    To improve its poor aqueous solubility and stability, the potential chemopreventive agent quercetin was encapsulated in freeze-dried polymeric micelles by a thin film hydration and vacuum freeze-drying process before being used for glioma chemotherapy. The micelle characteristics, release profile, cellular uptake, intracellular drug concentration, transport across the blood-brain barrier, and antitumor efficiency in vivo were investigated. Results showed that the particle size of quercetin-loaded freeze-dried nanomicelles (QUE-FD-NMs) ranged from 20 to 80nm, with an efficiently sustained release profile. Increased intracellular uptake into Caco-2 cells with low cytotoxicity, efficient penetration of BBB, and powerful cytotoxicity on C6 glioma cells were observed. QUE-FD-NMs accumulated in tumor-bearing brain tissues and exhibited significant antitumor effects in vivo, which significantly benefited the survival of glioma-bearing mice. These findings suggest that freeze-drying micelles loaded with quercetin is a promising drug delivery method for glioma therapy. PMID:27242199

  2. Combination of lycopene, quercetin and poloxamer 188 alleviates anxiety and depression in 3-nitropropionic acid-induced Huntington’s disease in rats

    PubMed Central

    Jain, Dilpesh; Gangshettiwar, Arti

    2014-01-01

    Aim: The present study investigates synergistic effect of combination treatment of lycopene, quercetin and poloxamer188 in 3-nitropropionic acid (3-NP)-induced Huntington’s disease (HD). Materials and Methods: Anxiety and depression were induced in male Wistar rat by intra-peritoneal administration of 3-NP (10 mg/kg) for 14 days. Body weight was assessed on day 1, 7 and 14, whereas locomotion, anxiety and depression were assessed at the end of the experiment. Results: Administration of 3-NP induces HD like symptoms and produced a significant decrease in body weight on day 7 (P < 0.01)and day 14 (P < 0.001), further decreased locomotion, time spent and number of entries in light area as well as increased immobility period were observed. The rats treated with lycopene and quercetin alone significantly restore the body weight and locomotion count as well as alleviate anxiety and depression. However, combination treatment of lycopene and quercetin with and without poloxamer 188 produced more significant effect on body weight compared to Huntington control rats, but no significant effect was found between the treated groups. However, significant increased on locomotion, time spent and number of entries in light area and decreased immobility period was observed in the combination treated groups when compared to single drug therapy. Conclusion: Combination treatment of lycopene and quercetin with and without poloxamer 188 in HD more effectively alleviate anxiety and depression than single drug therapy. PMID:26401371

  3. Copper(II) Quercetin complexes in aqueous solutions: spectroscopic and kinetic properties

    NASA Astrophysics Data System (ADS)

    Torreggiani, Armida; Tamba, Maurizio; Trinchero, Andrea; Bonora, Sergio

    2005-06-01

    Quercetin (Querc), one of the most common dietary flavonols, was investigated in the presence of Cu(II) ions under basic conditions by different techniques in order to obtain some elucidation on the mechanism of its beneficial action against free radical-mediated damage. The spectroscopic studies (UV/Vis, Raman and IR) were useful to assess the relevant interaction of Querc with Cu(II) ions, the chelation sites and the dependence of the complex structure from the metal/ligand ratio. In the presence of a slight excess of the ligand (0.5 M/ L) Querc acts as a bidentate ligand trough the catechol moiety on B ring. At M/ L>1 the metal interaction also involves the C dbnd6 O group and a close hydroxyl group. Thermogravimetric analysis confirmed the stoichiometry of the proposed complexes. Information on the reactivity of the Cu(II) chelates towards oxidizing radicals ( rad OH, N3ṡ and Br2-ṡ) were obtained by the pulse radiolysis data. The chelates appear to fast react with these oxidizing radicals, giving rise to intermediates transients, namely resonance-stabilised phenoxyl radicals.

  4. Glucuronidated Quercetin Lowers Blood Pressure in Spontaneously Hypertensive Rats via Deconjugation

    PubMed Central

    Galindo, Pilar; Rodriguez-Gómez, Isabel; González-Manzano, Susana; Dueñas, Montserrat; Jiménez, Rosario; Menéndez, Carmen; Vargas, Félix; Tamargo, Juan; Santos-Buelga, Celestino; Pérez-Vizcaíno, Francisco; Duarte, Juan

    2012-01-01

    Background Chronic oral quercetin reduces blood pressure and restores endothelial dysfunction in hypertensive animals. However, quercetin (aglycone) is usually not present in plasma, because it is rapidly metabolized into conjugated, mostly inactive, metabolites. The aim of the study is to analyze whether deconjugation of these metabolites is involved in the blood pressure lowering effect of quercetin. Methodology/Principal Findings We have analyzed the effects on blood pressure and vascular function in vitro of the conjugated metabolites of quercetin (quercetin-3-glucuronide, Q3GA; isorhamnetin-3-glucuronide, I3GA; and quercetin-3′-sulfate, Q3'S) in spontaneously hypertensive rats (SHR). Q3GA and I3GA (1 mg/kg i.v.), but not Q3'S, progressively reduced mean blood pressure (MBP), measured in conscious SHR. The hypotensive effect of Q3GA was abolished in SHR treated with the specific inhibitor of β-glucuronidase, saccharic acid 1,4-lactone (SAL, 10 mg/ml). In mesenteric arteries, unlike quercetin, Q3GA had no inhibitory effect in the contractile response to phenylephrine after 30 min of incubation. However, after 1 hour of incubation Q3GA strongly reduced this contractile response and this effect was prevented by SAL. Oral administration of quercetin (10 mg/Kg) induced a progressive decrease in MBP, which was also suppressed by SAL. Conclusions Conjugated metabolites are involved in the in vivo antihypertensive effect of quercetin, acting as molecules for the plasmatic transport of quercetin to the target tissues. Quercetin released from its glucuronidated metabolites could be responsible for its vasorelaxant and hypotensive effect. PMID:22427863

  5. Modulation of BV-2 microglia functions by novel quercetin pivaloyl ester.

    PubMed

    Mrvová, Nataša; Škandík, Martin; Kuniaková, Marcela; Račková, Lucia

    2015-11-01

    Chronic inflammation in brain plays a critical role in major neurodegenerative diseases such as Alzheimer's, Parkinson's disease, stroke or multiple sclerosis. Microglia, resident macrophages and intristinc components of CNS, appear to be main effectors in this pathological process. Quercetin, a naturally occurring flavonoid, was proven to downregulate inflammatory genes in microglia. Synthetically modified quercetin, 3'-O-(3-chloropivaloyl) quercetin (CPQ), is assumed to possess better biological availability and enhanced antioxidant properties. In the present study, antineuroinflammatory capability of the novel compound CPQ was assessed in BV-2 microglial cells. Our data show that treatment with CPQ attenuated the production of the inflammatory mediators, nitric oxide (NO) and tumour necrosis factor-α (TNF-α), in LPS-stimulated microglia somewhat more efficiently than did quercetin (p > 0.05 for CPQ vs. quercetin-treated group). Also, protein level of inducible NO synthase (iNOS) in LPS-activated BV-2 microglia was to some extent more effectively supressed by CPQ than by unmodified flavonoid. In consistence with the extent of their effects on pro-inflammatory markers, CPQ and quercetin showed down-regulation of NFκB activation. This quercetin analogue caused also a decline in BV-2 microglia proliferation with interfering with cell cycle progression (p < 0.001 for CPQ vs. quercetin-treated group). However, CPQ did not remarkably affect cell viability. In addition, CPQ showed a minor better suppression of PMA-induced generation of superoxide than did quercetin. Neither CPQ nor quercetin influenced phagocytosis of BV-2 cells. These results point to the therapeutic potential of 3'-O-(3-chloropivaloyl)quercetin (CPQ) as a novel antiinflammatory drug in neurodegenerative diseases, mediating favourable modulation of pro-inflammatory functions of microglia.

  6. Inhibition of tobacco mosaic virus infection by quercetin and vitexin.

    PubMed

    Krcatović, E; Rusak, G; Bezić, N; Krajacić, M

    2008-01-01

    The flavonoids, quercetin and vitexin were proved to reduce lesion number in the local hosts Datura stramonium and Chenopodium amaranticolor infected with Tobacco mosaic virus (TMV). Both flavonoids also reduced the virus concentration in systemically infected tobacco plants. This effect was restricted to an early stage of infection and correlated with an induced synthesis of salicylic acid (SA) and kaempferol suggesting their possible defensive role in the infected plant tissue. Since the tested flavonoids did not bind to the virus particles, their antiphytoviral activity was probably not based on a direct virus inactivation.

  7. Long-term avoidance memory formation is associated with a transient increase in mushroom body synaptic complexes in leaf-cutting ants

    PubMed Central

    Falibene, Agustina; Roces, Flavio; Rössler, Wolfgang

    2015-01-01

    Long-term behavioral changes related to learning and experience have been shown to be associated with structural remodeling in the brain. Leaf-cutting ants learn to avoid previously preferred plants after they have proved harmful for their symbiotic fungus, a process that involves long-term olfactory memory. We studied the dynamics of brain microarchitectural changes after long-term olfactory memory formation following avoidance learning in Acromyrmex ambiguus. After performing experiments to control for possible neuronal changes related to age and body size, we quantified synaptic complexes (microglomeruli, MG) in olfactory regions of the mushroom bodies (MBs) at different times after learning. Long-term avoidance memory formation was associated with a transient change in MG densities. Two days after learning, MG density was higher than before learning. At days 4 and 15 after learning—when ants still showed plant avoidance—MG densities had decreased to the initial state. The structural reorganization of MG triggered by long-term avoidance memory formation clearly differed from changes promoted by pure exposure to and collection of novel plants with distinct odors. Sensory exposure by the simultaneous collection of several, instead of one, non-harmful plant species resulted in a decrease in MG densities in the olfactory lip. We hypothesize that while sensory exposure leads to MG pruning in the MB olfactory lip, the formation of long-term avoidance memory involves an initial growth of new MG followed by subsequent pruning. PMID:25904854

  8. Anthocyanin indexes, quercetin, kaempferol, and myricetin concentration in leaves and fruit of Abutilon theophrasti Medik. genetic resources

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Anthocyanin indexes, quercetin, kaempferol, and myricetin may provide industry with potential new medicines or nutraceuticals. Velvetleaf (Abutilon theophrasti Medik) leaves from 42 accessions were analyzed for anthocyanin indexes while both leaves and fruit were used for quercetin, kaempferol, and ...

  9. Quercetin, kaempferol, myricetin, and fatty acid content among several Hibiscus sabdariffa accession calyces based on maturity in a greenhouse

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Flavonols including quercetin, kaempferol, myricetin, and fatty acids in plants have many useful health attributes including antioxidants, cholesterol lowering, and cancer prevention. Six accessions of roselle, Hibiscus sabdariffa calyces were evaluated for quercetin, kaempferol, and myricetin conte...

  10. Quercetin suppresses insulin receptor signaling through inhibition of the insulin ligand–receptor binding and therefore impairs cancer cell proliferation

    SciTech Connect

    Wang, Feng; Yang, Yong

    2014-10-03

    Graphical abstract: - Highlights: • Quercetin inhibits insulin ligand–receptor interactions. • Quercetin reduces downstream insulin receptor signaling. • Quercetin blocks insulin induced glucose uptake. • Quercetin suppresses insulin stimulated cancer cell proliferation and tumor growth. - Abstract: Although the flavonoid quercetin is known to inhibit activation of insulin receptor signaling, the inhibitory mechanism is largely unknown. In this study, we demonstrate that quercetin suppresses insulin induced dimerization of the insulin receptor (IR) through interfering with ligand–receptor interactions, which reduces the phosphorylation of IR and Akt. This inhibitory effect further inhibits insulin stimulated glucose uptake due to decreased cell membrane translocation of glucose transporter 4 (GLUT4), resulting in impaired cancer cell proliferation. The effect of quercetin in inhibiting tumor growth was also evident in an in vivo model, indicating a potential future application for quercetin in the treatment of cancers.

  11. Effects of linseed and quercetin added to the diet of fattening lambs on the fatty acid profile and lipid antioxidant status of meat samples.

    PubMed

    Andrés, S; Morán, L; Aldai, N; Tejido, M L; Prieto, N; Bodas, R; Giráldez, F J

    2014-06-01

    Thirty-two Merino lambs fed barley straw and a concentrate formulated either with palm oil (CTRL group) or with linseed (+LS group), both alone or supplemented with quercetin (+QCT group or +LS+QCT group) were used to assess the effects of these dietary supplements on meat quality attributes. After being slaughtered, the longissimus thoracis muscles were used to study the fatty acid (FA) profile in detail, whilst longissimus lumborum slices were stored under refrigerated conditions to determine the lipid stability. Linseed increased the content of highly unsaturated n-3 long-chain fatty acid (20:5n-3; 22:5n-3; 22:6n-3). Interestingly, a significant increment of rumenic acid content (9c,11t-18:2) was observed when this seed was administered together with dietary quercetin. Moreover, the feeding of quercetin resulted in a reduction in the proportion of saturated FA and a decrease in lipid peroxidation of meat when the lambs were fed linseed. In conclusion, from both a nutritional and a commercial (shelf-life) point of view, it may be useful to include a source of quercetin when lambs are fed linseed diets.

  12. Protective effects of Quercetin and chronic moderate exercise (training) against oxidative stress in the liver tissue of streptozotocin-induced diabetic rats.

    PubMed

    Chiş, I C; Mureşan, A; Oros, A; Nagy, A L; Clichici, S

    2016-03-01

    Background To investigate the protective effects of Quercetin administration associated with chronic moderate exercise (training) on oxidative stress in the liver in streptozotocin-induced diabetic rats. Methods Diabetic rats that performed exercise training were subjected to a swimming training program (1 hour/day, 5 days/week, 4 weeks). The diabetic rats received natural antioxidant, Quercetin (20 mg/kg body weight/day) for 4 weeks. At the end of the study, all animals were sacrificed and liver samples were collected for estimation: some oxidative stress markers (malondialdehyde, MDA and protein carbonyls groups, PC), the activity of antioxidant enzymes (superoxide dismutase, SOD and catalase, CAT), reduced glutathione (GSH) level and reduced (GSH) and oxidized (GSSG) glutathione ratio. Results Diabetic rats submitted to exercise training showed significantly increased the oxidative stress markers (MDA and PC) and a reduction of antioxidant enzyme (SOD and CAT) activity, GSH level and GSH/ GSSG ratio in hepatic tissues. A decrease in the levels of oxidative stress markers associated with elevated activity of antioxidant enzymes, the GSH level and GSH/GSSG ratio in the hepatic tissue were observed in Quercetin-treated diabetic trained rats. Conclusions These findings suggest that Quercetin administration in association with chronic moderate exercise exerts a protective effect in diabetes by attenuating hyperglycemia-mediated oxidative stress in hepatic tissue. PMID:27030627

  13. Potential protective effects of quercetin and curcumin on paracetamol-induced histological changes, oxidative stress, impaired liver and kidney functions and haematotoxicity in rat.

    PubMed

    Yousef, Mokhtar I; Omar, Sahar A M; El-Guendi, Marwa I; Abdelmegid, Laila A

    2010-11-01

    The present study was carried out to evaluate the potential protective role of quercetin and curcumin against paracetamol-induced oxidative injury, liver damage and impairment of kidney function, as well as haematotoxicity in rats. Also, N-acetylcysteine was used to evaluate the potency of quercetin and curcumin. Paracetamol caused an elevation in thiobarbituric acid-reactive substances (TBARS) paralleled with significant decline in glutathione peroxidase, glutathione S-transferase, superoxide dismutase and catalase activities (in plasma, brain, lung, heart, liver, kidney and testes) and glutathione content (in lung, liver and kidney). The apparent oxidative injury was associated with evident hepatic necrosis confirmed in histological examination, elevated plasma transmainases, alkaline phosphatase and lactate dehydrogenase. Paracetamol reduced plasma total protein, albumin and globulin, while increased bilirubin, urea and creatinine, and induced haematotoxicity. The presence of quercetin or curcumin with paracetamol successfully mitigated the rise in TBARS and restored the activities of antioxidant enzymes compared to the group treated with both paracetamol and N-acetylcysteine. They also protected liver histology, normalized liver and kidney functions, which was more pronounced with curcumin. Therefore, it can be concluded that concomitant administration of quercetin or curcumin with paracetamol may be useful in reversing the toxicity of the drug compared to N-acetylcysteine.

  14. Microsomal quercetin glucuronidation in rat small intestine depends on age and segment

    Technology Transfer Automated Retrieval System (TEKTRAN)

    UDP-glucuronosyltransferase (UGT) activity toward the flavonoid quercetin and UGT protein were characterized in 3 equidistant small intestine (SI) segments from 4, 12, 18, and 28 mo male F344 rats, n=8/age using villin to control for enterocyte content. SI microsomal intrinsic clearance of quercetin...

  15. [The efficacy of quercetin and tocopherol acetate in treating patients with Flexner's dysentery].

    PubMed

    Frolov, V M; Peresadin, N A; Khomutianskaia, N I; Pshenichnyĭ, I Ia

    1993-04-01

    Quercetin and tocopherol were given to 134 patients with Flexner's dysentery intramuscularly for 7 days; 154 patients received routine treatment. It was found that quercetin and tocopherol acetate enhanced normalization of clinical indices and restoration of the immune homeostasis. The above drugs are recommended for the complex treatment of dysentery.

  16. Preventive effect of dietary quercetin on disuse muscle atrophy by targeting mitochondria in denervated mice.

    PubMed

    Mukai, Rie; Matsui, Naoko; Fujikura, Yutaka; Matsumoto, Norifumi; Hou, De-Xing; Kanzaki, Noriyuki; Shibata, Hiroshi; Horikawa, Manabu; Iwasa, Keiko; Hirasaka, Katsuya; Nikawa, Takeshi; Terao, Junji

    2016-05-01

    Quercetin is a major dietary flavonoid in fruits and vegetables. We aimed to clarify the preventive effect of dietary quercetin on disuse muscle atrophy and the underlying mechanisms. We established a mouse denervation model by cutting the sciatic nerve in the right leg (SNX surgery) to lack of mobilization in hind-limb. Preintake of a quercetin-mixed diet for 14days before SNX surgery prevented loss of muscle mass and atrophy of muscle fibers in the gastrocnemius muscle (GM). Phosphorylation of Akt, a key phosphorylation pathway of suppression of protein degradation, was activated in the quercetin-mixed diet group with and without SNX surgery. Intake of a quercetin-mixed diet suppressed the generation of hydrogen peroxide originating from mitochondria and elevated mitochondrial peroxisome proliferator-activated receptor-γ coactivator 1α mRNA expression as well as NADH dehydrogenase 4 expression in the GM with SNX surgery. Quercetin and its conjugated metabolites reduced hydrogen peroxide production in the mitochondrial fraction obtained from atrophied muscle. In C2C12 myotubes, quercetin reached the mitochondrial fraction. These findings suggest that dietary quercetin can prevent disuse muscle atrophy by targeting mitochondria in skeletal muscle tissue through protecting mitochondria from decreased biogenesis and reducing mitochondrial hydrogen peroxide release, which can be related to decreased hydrogen peroxide production and/or improvements on antioxidant capacity of mitochondria. PMID:27133425

  17. Genetic expression profile analysis of the temporal inhibition of quercetin and naringenin on Lactobacillus rhamnosus GG

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The plant polyphenols, quercetin and naringenin, are considered healthy dietary compounds; however, little is known of their effects on the probiotic Lactobacillus rhamnosus GG (LGG). In this study, it was discovered that both quercetin and naringenin produced temporary inhibition of LGG growth, par...

  18. Effects of quercetin on pharmacokinetics of cefprozil in Chinese-Han male volunteers.

    PubMed

    Jia, Fei-Fei; Tan, Zhi-Rong; McLeod, Howard L; Chen, Yao; Ou-Yang, Dong-Sheng; Zhou, Hong-Hao

    2016-10-01

    1. The primary objective of this study was to evaluate the effects of quercetin on the pharmacokinetics of cefprozil. The secondary objective was to evaluate the safety of the combined use of cefprozil and quercetin. 2. An open-label, two-period, crossover phase I trial among 24 Han Chinese male subjects was conducted. Participants were given 500 mg of quercetin orally once daily for 15 d followed by single dose of cefprozil (500 mg) on day 15. Serum concentrations of cefprozil were then measured in all participants on day 15. A 15-d washout period was then assigned after which a 500 mg dose of cefprozil was administered and measured in the serum on day 36. 3. All subjects completed the trial, and no serious adverse events were reported. We measured mean serum concentrations of cefprozil in the presence and absence of quercetin in all participants. The maximum serum concentration of cefprozil in the presence of quercetin was 8.18 ug/ml (95% CI: 7.55-8.81) versus a maximum cefprozil concentration of 8.35 ug/ml (95% CI: 7.51-9.19) in the absence of quercetin. We conclude that the concurrent use of quercetin has no substantial effect on serum concentrations of orally administered cefprozil. 4. Co-administration of quercetin showed no statistically significant effects on the pharmacokinetics of cefprozil in healthy Chinese subjects.

  19. Quercetin induces mitochondrial biogenesis in experimental traumatic brain injury via the PGC-1α signaling pathway

    PubMed Central

    Li, Xiang; Wang, Handong; Gao, Yongyue; Li, Liwen; Tang, Chao; Wen, Guodao; Yang, Youqing; Zhuang, Zong; Zhou, Mengliang; Mao, Lei; Fan, Youwu

    2016-01-01

    Quercetin, a dietary flavonoid used as a food supplement, has been found to have protective effect against mitochondria damage after traumatic brain injury (TBI) in mice. However, the mechanisms underlying these effects are still not well understood. The aim of the present study was to investigate the effect of quercetin on the potential mechanism mediating these effects in the weight-drop model of TBI in male mice that were treated with quercetin or vehicle via intraperitoneal injection administration 30 min after TBI. Brain samples were collected 24 h later for analysis. Quercetin treatment upregulated the expression of PGC-1α and restored the level of cytochrome c, malondialdehyde (MDA) and superoxide dismutase (SOD). These results demonstrate that quercetin improves mitochondrial function in mice by improving the level of PGC-1α following TBI. PMID:27648146

  20. Quercetin induces mitochondrial biogenesis in experimental traumatic brain injury via the PGC-1α signaling pathway

    PubMed Central

    Li, Xiang; Wang, Handong; Gao, Yongyue; Li, Liwen; Tang, Chao; Wen, Guodao; Yang, Youqing; Zhuang, Zong; Zhou, Mengliang; Mao, Lei; Fan, Youwu

    2016-01-01

    Quercetin, a dietary flavonoid used as a food supplement, has been found to have protective effect against mitochondria damage after traumatic brain injury (TBI) in mice. However, the mechanisms underlying these effects are still not well understood. The aim of the present study was to investigate the effect of quercetin on the potential mechanism mediating these effects in the weight-drop model of TBI in male mice that were treated with quercetin or vehicle via intraperitoneal injection administration 30 min after TBI. Brain samples were collected 24 h later for analysis. Quercetin treatment upregulated the expression of PGC-1α and restored the level of cytochrome c, malondialdehyde (MDA) and superoxide dismutase (SOD). These results demonstrate that quercetin improves mitochondrial function in mice by improving the level of PGC-1α following TBI.

  1. Quercetin induces mitochondrial biogenesis in experimental traumatic brain injury via the PGC-1α signaling pathway.

    PubMed

    Li, Xiang; Wang, Handong; Gao, Yongyue; Li, Liwen; Tang, Chao; Wen, Guodao; Yang, Youqing; Zhuang, Zong; Zhou, Mengliang; Mao, Lei; Fan, Youwu

    2016-01-01

    Quercetin, a dietary flavonoid used as a food supplement, has been found to have protective effect against mitochondria damage after traumatic brain injury (TBI) in mice. However, the mechanisms underlying these effects are still not well understood. The aim of the present study was to investigate the effect of quercetin on the potential mechanism mediating these effects in the weight-drop model of TBI in male mice that were treated with quercetin or vehicle via intraperitoneal injection administration 30 min after TBI. Brain samples were collected 24 h later for analysis. Quercetin treatment upregulated the expression of PGC-1α and restored the level of cytochrome c, malondialdehyde (MDA) and superoxide dismutase (SOD). These results demonstrate that quercetin improves mitochondrial function in mice by improving the level of PGC-1α following TBI. PMID:27648146

  2. A Molecularly Imprinted Polymer with Incorporated Graphene Oxide for Electrochemical Determination of Quercetin

    PubMed Central

    Sun, Si; Zhang, Mengqi; Li, Yijun; He, Xiwen

    2013-01-01

    The molecularly imprinted polymer based on polypyrrole film with incorporated graphene oxide was fabricated and used for electrochemical determination of quercetin. The electrochemical behavior of quercetin on the modified electrode was studied in detail using differential pulse voltammetry. The oxidation peak current of quercetin in B-R buffer solution (pH = 3.5) at the modified electrode was regressed with the concentration in the range from 6.0 × 10−7 to 1.5 × 10−5 mol/L (r2 = 0.997) with a detection limit of 4.8 × 10−8 mol/L (S/N = 3). This electrode showed good stability and reproducibility. In the above mentioned range, rutin or morin which has similar structures and at the same concentration as quercetin did not interfere with the determination of quercetin. The applicability of the method for complex matrix analysis was also evaluated. PMID:23698263

  3. Antioxidative Properties and Effect of Quercetin and Its Glycosylated Form (Rutin) on Acetylcholinesterase and Butyrylcholinesterase Activities.

    PubMed

    Ademosun, Ayokunle O; Oboh, Ganiyu; Bello, Fatai; Ayeni, Peluola O

    2016-10-01

    This study sought to investigate the anticholinesterase and antioxidative properties of quercetin and its glycosylated conjugate, rutin. The in vitro inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities, inhibition of Fe(2+)-induced lipid peroxidation in rat's brain homogenates, radicals scavenging, and Fe(2+)-chelating abilities of the flavonoids were investigated in vitro with concentrations of the samples ranging from 0.06 to 0.6 mM. Quercetin had significantly higher AChE and BChE inhibitory abilities than rutin. Quercetin also had stronger inhibition of Fe(2+)-induced lipid peroxidation in rat's brain homogenates. Similarly, quercetin had higher radical scavenging abilities than rutin. Quercetin also had stronger Fe(2+)-chelating ability than rutin. The inhibition of cholinesterases and antioxidative properties are possible mechanisms by which the flavonoids can be used in the management of oxidative stress-induced neurodegeneration.

  4. Combination of Quercetin and 2-Methoxyestradiol Enhances Inhibition of Human Prostate Cancer LNCaP and PC-3 Cells Xenograft Tumor Growth

    PubMed Central

    Yang, Feiya; Song, Liming; Wang, Huiping; Wang, Jun; Xu, Zhiqing; Xing, Nianzeng

    2015-01-01

    Quercetin and 2-Methoxyestradiol (2-ME) are promising anti-cancer substances. Our previous in vitro study showed that quercetin synergized with 2-Methoxyestradiol exhibiting increased antiproliferative and proapoptotic activity in both androgen-dependent LNCaP and androgen-independent PC-3 human prostate cancer cell lines. In the present study, we determined whether their combination could inhibit LNCaP and PC-3 xenograft tumor growth in vivo and explored the underlying mechanism. Human prostate cancer LNCaP and PC-3 cells were inoculated subcutaneously in male BALB/c nude mice. When xenograft tumors reached about 100 mm3, mice were randomly allocated to vehicle control, quercetin or 2-Methoxyestradiol singly treated and combination treatment groups. After therapeutic intervention for 4 weeks, combination treatment of quercetin and 2-ME i) significantly inhibited prostate cancer xenograft tumor growth by 46.8% for LNCaP and 51.3% for PC-3 as compared to vehicle control group, more effective than quercetin (28.4% for LNCaP, 24.8% for PC3) or 2-ME (32.1% for LNCaP, 28.9% for PC3) alone; ii) was well tolerated by BALB/c mice and no obvious toxic reactions were observed; iii) led to higher Bax/Bcl-2 ratio, cleaved caspase-3 protein expression and apoptosis rate; and iv) resulted in lower phosphorylated AKT (pAKT) protein level, vascular endothelial growth factor protein and mRNA expression, microvascular density and proliferation rate than single drug treatment. These effects were more remarkable compared to vehicle group. Therefore, combination of quercetin and 2-ME can serve as a novel clinical treatment regimen owning the potential of enhancing antitumor effect on prostate cancer in vivo and lessening the dose and side effects of either quercetin or 2-ME alone. These in vivo results will lay a further solid basis for subsequent researches on this novel therapeutic regimen in human prostate cancer. PMID:26011145

  5. Dietary quercetin exacerbates the development of estrogen-induced breast tumors in female ACI rats

    SciTech Connect

    Singh, Bhupendra; Mense, Sarah M.; Bhat, Nimee K.; Putty, Sandeep; Guthiel, William A.; Remotti, Fabrizio; Bhat, Hari K.

    2010-09-01

    Phytoestrogens are plant compounds that structurally mimic the endogenous estrogen 17{beta}-estradiol (E{sub 2}). Despite intense investigation, the net effect of phytoestrogen exposure on the breast remains unclear. The objective of the current study was to examine the effects of quercetin on E{sub 2}-induced breast cancer in vivo. Female ACI rats were given quercetin (2.5 g/kg food) for 8 months. Animals were monitored weekly for palpable tumors, and at the end of the experiment, rats were euthanized, breast tumor and different tissues excised so that they could be examined for histopathologic changes, estrogen metabolic activity and oxidant stress. Quercetin alone did not induce mammary tumors in female ACI rats. However, in rats implanted with E{sub 2} pellets, co-exposure to quercetin did not protect rats from E{sub 2}-induced breast tumor development with 100% of the animals developing breast tumors within 8 months of treatment. No changes in serum quercetin levels were observed in quercetin and quercetin + E{sub 2}-treated groups at the end of the experiment. Tumor latency was significantly decreased among rats from the quercetin + E{sub 2} group relative to those in the E{sub 2} group. Catechol-O-methyltransferase (COMT) activity was significantly downregulated in quercetin-exposed mammary tissue. Analysis of 8-isoprostane F{sub 2{alpha}} (8-iso-PGF{sub 2{alpha}}) levels as a marker of oxidant stress showed that quercetin did not decrease E{sub 2}-induced oxidant stress. These results indicate that quercetin (2.5 g/kg food) does not confer protection against breast cancer, does not inhibit E{sub 2}-induced oxidant stress and may exacerbate breast carcinogenesis in E{sub 2}-treated ACI rats. Inhibition of COMT activity by quercetin may expose breast cells chronically to E{sub 2} and catechol estrogens. This would permit longer exposure times to the carcinogenic metabolites of E{sub 2} and chronic exposure to oxidant stress as a result of metabolic redox

  6. Neuroprotective Role of Nanoencapsulated Quercetin in Combating Ischemia-Reperfusion Induced Neuronal Damage in Young and Aged Rats

    PubMed Central

    Ghosh, Aparajita; Sarkar, Sibani; Mandal, Ardhendu K.; Das, Nirmalendu

    2013-01-01

    Cerebral stroke is the leading cause of death and permanent disability among elderly people. In both humans and animals, cerebral ischemia damages the nerve cells in vulnerable regions of the brain, viz., hippocampus, cerebral cortex, cerebellum, and hypothalamus. The present study was conducted to evaluate the therapeutic efficacy of nanoencapsulated quercetin (QC) in combating ischemia-reperfusion-induced neuronal damage in young and aged Swiss Albino rats. Cerebral ischemia was induced by occlusion of the common carotid arteries of both young and aged rats followed by reperfusion. Nanoencapsulated quercetin (2.7 mg/kg b wt) was administered to both groups of animals via oral gavage two hours prior to ischemic insults as well as post-operation till day 3. Cerebral ischemia and 30 min consecutive reperfusion caused a substantial increase in lipid peroxidation, decreased antioxidant enzyme activities and tissue osmolality in different brain regions of both groups of animals. It also decreased mitochondrial membrane microviscosity and increased reactive oxygen species (ROS) generation in different brain regions of young and aged rats. Among the brain regions studied, the hippocampus appeared to be the worst affected region showing increased upregulation of iNOS and caspase-3 activity with decreased neuronal count in the CA1 and CA3 subfields of both young and aged rats. Furthermore, three days of continuous reperfusion after ischemia caused massive damage to neuronal cells. However, it was observed that oral treatment of nanoencapsulated quercetin (2.7 mg/kg b wt) resulted in downregulation of iNOS and caspase-3 activities and improved neuronal count in the hippocampal subfields even 3 days after reperfusion. Moreover, the nanoformulation imparted a significant level of protection in the antioxidant status in different brain regions, thus contributing to a better understanding of the given pathophysiological processes causing ischemic neuronal damage. PMID:23620721

  7. Hypoxia induces an increase in intracellular magnesium via transient receptor potential melastatin 7 (TRPM7) channels in rat hippocampal neurons in vitro.

    PubMed

    Zhang, Jing; Zhao, Fengbo; Zhao, Yin; Wang, Jing; Pei, Lei; Sun, Ning; Shi, Jing

    2011-06-10

    TRPM7, a divalent cation channel, plays an important role in neurons damaged from cerebral ischemia due to permitting intracellular calcium overload. This study aimed to explore whether magnesium was transported via a TRPM7 channel into the intracellular space of rat hippocampal neurons after 1 h of oxygen-glucose deprivation (OGD) and acute chemical ischemia (CI) by using methods of the Mg(2+) fluorescent probe Mag-Fura-2 to detect intracellular magnesium concentration ([Mg(2+)](i)) and flame atomic absorption spectrometry to measure extracellular magnesium concentration ([Mg(2+)](o)). The results showed that the neuronal [Mg(2+)](i) was 1.51-fold higher after 1 h of OGD at a basal level, and the increase of neuronal [Mg(2+)](i) reached a peak after 1 h of OGD and was kept for 60 min with re-oxygenation. Meanwhile, the [Mg(2+)](o) decreased after 1 h of OGD and recovered to the pre-ischemic level within 15 min after re-oxygenation. In the case of CI, the [Mg(2+)](i) peak immediately appeared in hippocampal neurons. This increase of [Mg(2+)](i) declined by removing extracellular magnesium in OGD or CI. Furthermore, by using Gd(3+) or 2-aminoethoxydiphenyl borate to inhibit TRPM7 channels, the [Mg(2+)](i) increase, which was induced by OGD or CI, was attenuated without altering the basal level of [Mg(2+)](i). By silencing TRPM7 with shRNA in hippocampal neurons, it was found that not only was the increase of [Mg(2+)](i) induced by OGD or CI but also the basal levels of [Mg(2+)](i) were attenuated. In contrast, overexpression of TRPM7 in HEK293 cells exaggerated both the basal levels and increased [Mg(2+)](i) after 1 h of OGD/CI. These results suggest that anoxia induced the increase of [Mg(2+)](i) via TRPM7 channels in rat hippocampal neurons. PMID:21487014

  8. Quercetin induces HepG2 cell apoptosis by inhibiting fatty acid biosynthesis

    PubMed Central

    ZHAO, PENG; MAO, JUN-MIN; ZHANG, SHU-YUN; ZHOU, ZE-QUAN; TAN, YANG; ZHANG, YU

    2014-01-01

    Quercetin can inhibit the growth of cancer cells with the ability to act as a ‘chemopreventer’. Its cancer-preventive effect has been attributed to various mechanisms, including the induction of cell-cycle arrest and/or apoptosis, as well as its antioxidant functions. Quercetin can also reduce adipogenesis. Previous studies have shown that quercetin has potent inhibitory effects on animal fatty acid synthase (FASN). In the present study, activity of quercetin was evaluated in human liver cancer HepG2 cells. Intracellular FASN activity was calculated by measuring the absorption of NADPH via a spectrophotometer. MTT assay was used to test the cell viability, immunoblot analysis was performed to detect FASN expression levels and the apoptotic effect was detected by Hoechst 33258 staining. In the present study, it was found that quercetin could induce apoptosis in human liver cancer HepG2 cells with overexpression of FASN. This apoptosis was accompanied by the reduction of intracellular FASN activity and could be rescued by 25 or 50 μM exogenous palmitic acids, the final product of FASN-catalyzed synthesis. These results suggested that the apoptosis induced by quercetin was via the inhibition of FASN. These findings suggested that quercetin may be useful for preventing human liver cancer. PMID:25009654

  9. Effect of Quercetin on Hepatitis C Virus Life Cycle: From Viral to Host Targets.

    PubMed

    Rojas, Ángela; Del Campo, Jose A; Clement, Sophie; Lemasson, Matthieu; García-Valdecasas, Marta; Gil-Gómez, Antonio; Ranchal, Isidora; Bartosch, Birke; Bautista, Juan D; Rosenberg, Arielle R; Negro, Francesco; Romero-Gómez, Manuel

    2016-08-22

    Quercetin is a natural flavonoid, which has been shown to have anti hepatitis C virus (HCV) properties. However, the exact mechanisms whereby quercetin impacts the HCV life cycle are not fully understood. We assessed the effect of quercetin on different steps of the HCV life cycle in Huh-7.5 cells and primary human hepatocytes (PHH) infected with HCVcc. In both cell types, quercetin significantly decreased i) the viral genome replication; ii) the production of infectious HCV particles and iii) the specific infectivity of the newly produced viral particles (by 85% and 92%, Huh7.5 and PHH respectively). In addition, when applied directly on HCV particles, quercetin reduced their infectivity by 65%, suggesting that it affects the virion integrity. Interestingly, the HCV-induced up-regulation of diacylglycerol acyltransferase (DGAT) and the typical localization of the HCV core protein to the surface of lipid droplets, known to be mediated by DGAT, were both prevented by quercetin. In conclusion, quercetin appears to have direct and host-mediated antiviral effects against HCV.

  10. Effect of Quercetin on Hepatitis C Virus Life Cycle: From Viral to Host Targets

    PubMed Central

    Rojas, Ángela; Del Campo, Jose A.; Clement, Sophie; Lemasson, Matthieu; García-Valdecasas, Marta; Gil-Gómez, Antonio; Ranchal, Isidora; Bartosch, Birke; Bautista, Juan D.; Rosenberg, Arielle R.; Negro, Francesco; Romero-Gómez, Manuel

    2016-01-01

    Quercetin is a natural flavonoid, which has been shown to have anti hepatitis C virus (HCV) properties. However, the exact mechanisms whereby quercetin impacts the HCV life cycle are not fully understood. We assessed the effect of quercetin on different steps of the HCV life cycle in Huh-7.5 cells and primary human hepatocytes (PHH) infected with HCVcc. In both cell types, quercetin significantly decreased i) the viral genome replication; ii) the production of infectious HCV particles and iii) the specific infectivity of the newly produced viral particles (by 85% and 92%, Huh7.5 and PHH respectively). In addition, when applied directly on HCV particles, quercetin reduced their infectivity by 65%, suggesting that it affects the virion integrity. Interestingly, the HCV-induced up-regulation of diacylglycerol acyltransferase (DGAT) and the typical localization of the HCV core protein to the surface of lipid droplets, known to be mediated by DGAT, were both prevented by quercetin. In conclusion, quercetin appears to have direct and host-mediated antiviral effects against HCV. PMID:27546480

  11. Quercetin-3-O-glucuronide induces ABCA1 expression by LXRα activation in murine macrophages

    SciTech Connect

    Ohara, Kazuaki; Wakabayashi, Hideyuki; Taniguchi, Yoshimasa; Shindo, Kazutoshi; Yajima, Hiroaki; Yoshida, Aruto

    2013-11-29

    Highlights: •The major circulating quercetin metabolite (Q3GA) activated LXRα. •Q3GA induced ABCA1 via LXRα activation in macrophages. •Nelumbo nucifera leaf extracts contained quercetin glycosides. •N. nucifera leaf extract feeding elevated HDLC in mice. -- Abstract: Reverse cholesterol transport (RCT) removes excess cholesterol from macrophages to prevent atherosclerosis. ATP-binding cassette, subfamily A, member 1 (ABCA1) is a crucial cholesterol transporter involved in RCT to produce high density lipoprotein-cholesterol (HDLC), and is transcriptionally regulated by liver X receptor alpha (LXRα), a nuclear receptor. Quercetin is a widely distributed flavonoid in edible plants which prevented atherosclerosis in an animal model. We found that quercetin-3-O-glucuronide (Q3GA), a major quercetin metabolite after absorption from the digestive tract, enhanced ABCA1 expression, in vitro, via LXRα in macrophages. In addition, leaf extracts of a traditional Asian edible plant, Nelumbo nucifera (NNE), which contained abundant amounts of quercetin glycosides, significantly elevated plasma HDLC in mice. We are the first to present experimental evidence that Q3GA induced ABCA1 in macrophages, and to provide an alternative explanation to previous studies on arteriosclerosis prevention by quercetin.

  12. Quercetin Influences Quorum Sensing in Food Borne Bacteria: In-Vitro and In-Silico Evidence

    PubMed Central

    Gopu, Venkadesaperumal; Meena, Chetan Kumar; Shetty, Prathapkumar Halady

    2015-01-01

    Quorum sensing (QS) plays a vital role in regulating the virulence factor of many food borne pathogens, which causes severe public health risk. Therefore, interrupting the QS signaling pathway may be an attractive strategy to combat microbial infections. In the current study QS inhibitory activity of quercetin and its anti-biofilm property was assessed against food-borne pathogens using a bio-sensor strain. In addition in-silico techniques like molecular docking and molecular dynamics simulation studies were applied to screen the quercetin’s potentiality as QS inhibitor. Quercetin (80μg/ml) showed the significant reduction in QS-dependent phenotypes like violacein production, biofilm formation, exopolysaccharide (EPS) production, motility and alginate production in a concentration-dependent manner. Synergistic activity of conventional antibiotics with quercetin enhanced the susceptibility of all tested pathogens. Furthermore, Molecular docking analysis revealed that quercetin binds more rigidly with LasR receptor protein than the signaling compound with docking score of -9.17Kcal/mol. Molecular dynamics simulation predicted that QS inhibitory activity of quercetin occurs through the conformational changes between the receptor and quercetin complex. Above findings suggest that quercetin can act as a competitive inhibitor for signaling compound towards LasR receptor pathway and can serve as a novel QS-based antibacterial/anti-biofilm drug to manage food-borne pathogens. PMID:26248208

  13. Effect of Quercetin on Hepatitis C Virus Life Cycle: From Viral to Host Targets.

    PubMed

    Rojas, Ángela; Del Campo, Jose A; Clement, Sophie; Lemasson, Matthieu; García-Valdecasas, Marta; Gil-Gómez, Antonio; Ranchal, Isidora; Bartosch, Birke; Bautista, Juan D; Rosenberg, Arielle R; Negro, Francesco; Romero-Gómez, Manuel

    2016-01-01

    Quercetin is a natural flavonoid, which has been shown to have anti hepatitis C virus (HCV) properties. However, the exact mechanisms whereby quercetin impacts the HCV life cycle are not fully understood. We assessed the effect of quercetin on different steps of the HCV life cycle in Huh-7.5 cells and primary human hepatocytes (PHH) infected with HCVcc. In both cell types, quercetin significantly decreased i) the viral genome replication; ii) the production of infectious HCV particles and iii) the specific infectivity of the newly produced viral particles (by 85% and 92%, Huh7.5 and PHH respectively). In addition, when applied directly on HCV particles, quercetin reduced their infectivity by 65%, suggesting that it affects the virion integrity. Interestingly, the HCV-induced up-regulation of diacylglycerol acyltransferase (DGAT) and the typical localization of the HCV core protein to the surface of lipid droplets, known to be mediated by DGAT, were both prevented by quercetin. In conclusion, quercetin appears to have direct and host-mediated antiviral effects against HCV. PMID:27546480

  14. Quercetin 3-rhamnoside exerts antiinfluenza A virus activity in mice.

    PubMed

    Choi, Hwa Jung; Song, Jae Hyoung; Kwon, Dur Han

    2012-03-01

    Our previous report showed that quercetin 3-rhamnoside (Q3R) possessed antiviral activity against influenza A/WS/33 virus in vitro. The present study evaluated the effect of Q3R on influenza A/WS/33 virus infected mice. Mice orally treated with Q3R (6.25 mg/kg per dose) at 2 h before and once daily for 6 days after influenza virus infection showed significant decreases in weight loss, and decreased mortality. Lung virus titers of mice killed at 6 days after infection were about 2000 times lower than that of the placebo-treated control mice and about two times lower than that for the oseltamivir-treated mice. Furthermore, histological evaluation showed that administration of Q3R delayed the development and progression of pulmonary lesions. Therefore, Q3R could be an attractive lead for the development of antiviral agents against influenza virus.

  15. Comparison of poly(ε-caprolactone) chain lengths of poly(ε-caprolactone)-co-d-α-tocopheryl-poly(ethylene glycol) 1000 succinate nanoparticles for enhancement of quercetin delivery to SKBR3 breast cancer cells.

    PubMed

    Suksiriworapong, Jiraphong; Phoca, Kittisak; Ngamsom, Supakanda; Sripha, Kittisak; Moongkarndi, Primchanien; Junyaprasert, Varaporn Buraphacheep

    2016-04-01

    This study aimed to investigate the effect of the different hydrophobic chain lengths of poly(ε-caprolactone)-co-d-α-tocopheryl polyethylene glycol 1000 succinate (P(CL)-TPGS) copolymers on the nanoparticle properties and delivery efficiency of quercetin to SKBR3 breast cancer cells. The 5:1, 10:1 and 20:1 P(CL)-TPGS copolymers were fabricated and found to be composed of 25.0%, 45.2% and 66.8% of hydrophobic P(CL) chains with respect to the polymer chain, respectively. The DSC measurement indicated the microphase separation of P(CL) and TPGS segments. The crystallization of P(CL) segment occurred when the P(CL) chain was higher than 25% due to the restricted mobility of P(CL) by TPGS. The longer P(CL) chain had the higher crystallinity while decreasing the crystallinity of TPGS segment. The increasing P(CL) chain length increased the particle size of P(CL)-TPGS nanoparticles from 20 to 205 nm and enhanced the loading capacity of quercetin due to the more hydrophobicity of the nanoparticle core. The release of quercetin was retarded by an increase in P(CL) chain length associated with the increasing hydrophobicity and crystallinity of P(CL)-TPGS copolymers. The P(CL)-TPGS nanoparticles potentiated the toxicity of quercetin to SKBR3 cells by at least 2.9 times compared to the quercetin solution. The cellular uptake of P(CL)-TPGS nanoparticles by SKBR3 cells occurred through cholesterol-dependent endocytosis. The 10:1 P(CL)-TPGS nanoparticles showed the highest toxicity and uptake efficiency and could be potentially used for the delivery of quercetin to breast cancer cells.

  16. Evaluation of terrestrial carbon cycle models with atmospheric CO2 measurements: Results from transient simulations considering increasing CO2, climate, and land-use effects

    USGS Publications Warehouse

    Dargaville, R.J.; Heimann, Martin; McGuire, A.D.; Prentice, I.C.; Kicklighter, D.W.; Joos, F.; Clein, J.S.; Esser, G.; Foley, J.; Kaplan, J.; Meier, R.A.; Melillo, J.M.; Moore, B.; Ramankutty, N.; Reichenau, T.; Schloss, A.; Sitch, S.; Tian, H.; Williams, L.J.; Wittenberg, U.

    2002-01-01

    An atmospheric transport model and observations of atmospheric CO2 are used to evaluate the performance of four Terrestrial Carbon Models (TCMs) in simulating the seasonal dynamics and interannual variability of atmospheric CO2 between 1980 and 1991. The TCMs were forced with time varying atmospheric CO2 concentrations, climate, and land use to simulate the net exchange of carbon between the terrestrial biosphere and the atmosphere. The monthly surface CO2 fluxes from the TCMs were used to drive the Model of Atmospheric Transport and Chemistry and the simulated seasonal cycles and concentration anomalies are compared with observations from several stations in the CMDL network. The TCMs underestimate the amplitude of the seasonal cycle and tend to simulate too early an uptake of CO2 during the spring by approximately one to two months. The model fluxes show an increase in amplitude as a result of land-use change, but that pattern is not so evident in the simulated atmospheric amplitudes, and the different models suggest different causes for the amplitude increase (i.e., CO2 fertilization, climate variability or land use change). The comparison of the modeled concentration anomalies with the observed anomalies indicates that either the TCMs underestimate interannual variability in the exchange of CO2 between the terrestrial biosphere and the atmosphere, or that either the variability in the ocean fluxes or the atmospheric transport may be key factors in the atmospheric interannual variability.

  17. Intermittent Suckling Causes a Transient Increase in Cortisol That Does Not Appear to Compromise Selected Measures of Piglet Welfare and Stress †

    PubMed Central

    Turpin, Diana L.; Langendijk, Pieter; Chen, Tai-Yuan; Lines, David; Pluske, John R.

    2016-01-01

    Simple Summary This study assessed the effects intermittent suckling (IS) had on physiological and behavioral indices of piglets before and after weaning. Piglets were allocated to either a control treatment (conventional weaning) or an IS treatment (separation from the sow for 8 h per day starting the week before weaning). Apart from an initial peak in cortisol at the start of IS, piglets subjected to IS did not show physiological changes suggestive of a chronic stress response before and after weaning. The event of weaning still caused a decrease in growth rate and an increase in white blood cell parameters in both treatment groups. However, the IS piglets tended to gain more weight in the second half of the week after weaning. The results of this study suggest that short periods of separation (e.g., 8 h/day) do not appear to compromise piglet welfare over the peri-weaning period. Abstract This study tested the hypothesis that piglets subjected to intermittent suckling (IS) would show changes in physiological and behavioral indices indicative of compromised welfare in the peri-weaning period. A total of 21 primiparous sows and their litters were allocated to either a control treatment (n = 10) where piglets were weaned conventionally, or an IS treatment (n = 11) where piglets were separated daily from their sows for 8 h starting the week before weaning. Performance, physiological and behavioral measures were taken at various time points during the week before and after weaning. Plasma cortisol levels were higher (p = 0.01) in IS piglets 7 d before weaning. Regardless of treatment, the N:L ratio at 3 d and 7 d after weaning was higher (p < 0.05) than that at 1 d before weaning. The IS piglets ate more creep feed during lactation (p < 0.05), and there was a tendency for the IS piglets to gain more weight between 3 d and 7 d after weaning (p < 0.1). This study showed that, aside from an increase in cortisol at the start of IS, piglets subjected to IS did not display

  18. The antimetastatic drug NAMI-A potentiates the phenylephrine-induced contraction of aortic smooth muscle cells and induces a transient increase in systolic blood pressure.

    PubMed

    Vadori, M; Florio, C; Groppo, B; Cocchietto, M; Pacor, S; Zorzet, S; Candussio, L; Sava, G

    2015-07-01

    The ruthenium-based drug imidazolium trans-imidazoledimethylsulphoxidetetrachlorido ruthenate (NAMI-A) is a novel antitumour drug under clinical evaluation. In this study, NAMI-A is tested on aortic rings in vitro and on the systolic blood pressure in vivo with the aim of evaluating its effects on smooth muscle cells and, more in general, on the vascular system. Pre-incubation of aortic rings with 10 µM NAMI-A for 10 min potentiates the contraction induced by phenylephrine (PE). The reduction of the B max value of [(3)H]-prazosin bound to NAMI-A-treated aortic rings and the ability of NAMI-A to displace [(3)H]-prazosin and [(3)H]-IP3 binding by 25 and 42%, respectively, suggest the involvement of α1-adrenoceptor in mediating the effects on smooth muscle cells. NAMI-A also decreases the number of maximal sites of [(3)H]-prazosin bound to kidney membrane preparation from 34 to 24 fmol/mg proteins. A single i.p. dose (105 mg/kg) or a repeated treatment for 6 consecutive days (17 mg/kg/day) in Wistar rats increases the systolic blood pressure, respectively, 1 h and 3 days after treatment, and the responsiveness of rat aortic rings to PE. Atomic absorption spectroscopy confirms the presence of ruthenium in the aortic rings excised from the treated rats. These findings suggest monitoring the cardiovascular parameters when the drug is used in humans for treating cancer patients, particularly if the drug is associated with chemicals that are potentially active at the cardiovascular level.

  19. Comparative effect of pioglitazone, quercetin and hydroxy citric acid on the status of lipid peroxidation and antioxidants in experimental non-alcoholic steatohepatitis.

    PubMed

    Surapaneni, K M; Jainu, M

    2014-02-01

    Oxidative stress is one of the key mechanisms responsible for liver damage and disease progression in non-alcoholic steatohepatitis (NASH). Antioxidants try to combat the oxidative stress and minimise the oxidative stress. In this study, the comparative effect of pioglitazone, quercetin and hydroxy citric acid on lipid peroxidation and antioxidants in experimentally induced NASH has been studied. The levels of lipid peroxidation products, malondialdehyde (MDA), glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione-S-transferase (GST) were estimated in experimental NASH. The levels of lipid peroxidation products (MDA) have been significantly increased in experimentally induced NASH group compared to the control group. The experimental NASH rats treated with pioglitazone, quercetin and with hydroxy citric acid showed significant reduction in MDA levels when compared with that of NASH induced group. Non enzymatic antioxidant such as GSH and antioxidant enzymes such as catalase, SOD, GPx, GR, and GST were decreased significantly in experimental NASH, compared to that of control group. The experimental NASH rats treated with pioglitazone showed marked increase in the levels of GSH, catalase and SOD but no significant effect on the levels of GPx, GR and GST levels when compared to the experimentally induced NASH group. Experimental NASH rats treated with hydroxy citric acid showed marked increase in the levels of GSH and catalase but no significant effect on the levels of SOD, GPx, GR and GST levels when compared to the experimentally induced NASH group. On contrary to these two drugs, the experimental NASH rats treated with quercetin showed significant increase in the levels of antioxidants as follows: GSH, catalase, SOD, GPx, GR and GST when compared with that of NASH induced group. We concluded that the levels of nonenzymatic and enzymatic antioxidants found to be decreased in

  20. Preparation and characterization of quercetin-loaded lipid liquid crystalline systems.

    PubMed

    Linkevičiūtė, A; Misiūnas, A; Naujalis, E; Barauskas, J

    2015-04-01

    The aim of the present study was to investigate mixtures of soy phosphatidylcholine (SPC) and glycerol dioleate (GDO) as encapsulation matrices for antioxidant quercetin. The effects of quercetin loading into non-aqueous formulations, non-lamellar liquid crystalline phases and their colloidal dispersions were studied by using synchrotron small angle X-ray diffraction, dynamic light scattering, cryogenic electron microscopy and high performance liquid chromatography. Quercetin incorporation is discussed in the context of lipid aggregation behavior, self-assembled nanostructure and chemical stability. The obtained results show that SPC/GDO-based formulations can incorporate relatively high amounts of quercetin and serve as liquid crystalline delivery vehicles in the form of bulk phases or colloidal dispersions.

  1. Exploration of the kinetic and thermochemical abilities for the free radical scavenging of two quercetin conformers

    NASA Astrophysics Data System (ADS)

    Mendoza-Wilson, Ana María; Sotelo-Mundo, Rogerio R.; Balandrán-Quintana, René R.; Glossman-Mitnik, Daniel; Sántiz-gómez, Marco a.; García-orozco, karina D.

    2010-09-01

    Quercetin has a great antioxidant potential due to its large capacity for free radical scavenging. Although it has been found that conformational changes have a profound effect on its chemical properties, there are few studies where conformation is associated with the antioxidant activity. The aim of this investigation was to explore the kinetic and the thermochemical abilities of two quercetin conformers for the free radical scavenging. Quercetin unhydrate (QUH) and quercetin dihydrate (QDH) conformers were studied employing 2,2-diphenyl-1-picrylhydrazyl (DPPH rad ) as in vitro radical model, and catechol and 4-hexyl-resorcinol as reference systems, for identifying the oxidation products. QDH showed to be most effective under conditions of free radical excess, while QUH was most effective when the flavonoid far exceeds the concentration of free radical. It was found, by means of experimental and computational methods, that 4'-OH, 3-OH and 3'-OH are the main reactive sites of both conformers.

  2. In silico QSAR analysis of quercetin reveals its potential as therapeutic drug for Alzheimer's disease

    PubMed Central

    Islam, Md. Rezaul; Zaman, Aubhishek; Jahan, Iffat; Chakravorty, Rajib; Chakraborty, Sajib

    2013-01-01

    Acetylcholine-esterase (AchE) inhibitors are one of the most potent drug molecules against Alzheimer's disease (AD). But, patients treated with current AchE inhibitors often experience severe side effects. Quercetin is a plant flavonoid compound which can act as AchE inhibitor and it may be a better alternative to current AchE inhibitors in terms of effectiveness with no or fewer side effects. Aims The aim of the study was to compare quercetin with conventional AchE inhibitors to search for a better drug candidate. Methods and materials Physico-chemical properties of conventional drugs and quercetin were predicted using bioinformatics tools. Molecular docking of these compounds on the active site of AchE was performed using AutoDock and comparative analysis was performed. Later, modification on the basic structure of quercetin with different functional groups was done to perform QSAR analysis. Result and discussion Quercetin showed a similar drug likeness score to the conventional drugs. The binding strength for quercetin in the active site of the enzyme was −8.8 kcal/mol, which was considerably higher than binding scores for some of the drugs such as donepezil (binding score −7.9 kcal/mol). Fifteen hydrogen bonds were predicted between quercetin and the enzyme whereas conventional drugs had fewer or even no hydrogen bonds. It implies that quercetin can act as a better inhibitor than conventional drugs. To find out even better inhibitor, similar structures of quercetin were searched through SIMCOMP database and a methylation in the 4-OH position of the molecule showed better binding affinity than parent quercetin. Quantitative structure activity relationship study indicated that O-4 methylation was specifically responsible for better affinity. Conclusion This in silico study has conclusively predicted the superiority of the natural compound quercetin over the conventional drugs as AchE inhibitor and it sets the need for further in-vitro study of this

  3. Detecting aseismic transients using seismicity

    NASA Astrophysics Data System (ADS)

    Reverso, T.; Marsan, D.; Helmstetter, A.

    2013-12-01

    Aseismic deformation transients occur in different tectonic context. In subduction zones, aseismic slip events are of paramount importance for understanding earthquake hazard, and for estimating the potential for future mega-thrust events. Aseismic slip is however difficult to detect except for the largest cases using GPS data. Here, we propose a systematic detection of aseismic deformation transients based on seismicity data alone. We search for transient increases in background seismicity rate, that would indicate the presence of an aseismic event. To that purpose, we make use of an ETAS model in space and time, to distinguish earthquakes due to background processes from aftershocks. We optimize the model parameters, and test the sensitivity of the results with changes in parameters. Given the 'best' model, we measure the statistical significance of the departure of the local (in time and space) background rate with the 'normal' background rate. Significant departure then indicates the need to temporary increase the background rate in order to explain the observed earthquake occurrences. We thus can single out such episodes of aseismic transients, and characterize their duration and spatial extent. Applying this method to the Aleutian subduction zone reveals several instances of aseismic deformation transients, at various spatial and temporal scales. We further investigate how these transients are organized along the subduction interface, and in time.

  4. A novel solid fluorescence method for the fast determination of quercetin in biological samples based on the quercetin-Al(III) complex imprinted polymer

    NASA Astrophysics Data System (ADS)

    Hu, Yufei; Feng, Ting; Li, Gongke

    2014-01-01

    In this work, a novel solid fluorescence method was proposed and applied to the fast determination of quercetin in urine and onion skin samples by using metal coordination imprinted polymer membrane, which was regarded as a recognition element. The quercetin-Al(III) imprinted polymer was immobilized in the microporous polypropylene fiber membrane via consecutive in situ polymerization. The CIP membrane had the porous, loose and layer upon layer structure. The CIP membrane was characterized by electron microscope photographs, infrared spectra, thermogravimetric analysis and solvent-resistant investigation. The extraction conditions including extraction solvent, extraction time, desorption solvent were optimized. Compared with MIP and NIP membrane, CIP membrane had been proved to be peculiar selective for quercetin even in presence of the structurally similar compounds such as kaempferol, rutin, naringenin and alpinetin. The CIP membrane was characteristic of high selectivity, stable and sensitive response to quercetin in polar environment. Under the optimum condition, there was a linear relationship between the state fluorescent response and the concentration of quercetin. The linear calibration range was over 0.02 mg L-1-0.80 mg L-1 with a detection limit of 5 μg L-1. The method was characteristic of flexible and good repeatability with relative standard deviation (RSD) of 4.1%. The proposed method was also successfully applied for the determination of quercetin in urine and onion skin samples without complicated pretreatment. The recoveries were 84.0-112.4% and RSDs varied from 1.5% to 6.8%. The results obtained by the proposed method agreed well with those obtained by HPLC method.

  5. Cardioprotective effects of quercetin against ischemia-reperfusion injury are age-dependent.

    PubMed

    Bartekova, M; Radosinska, J; Pancza, D; Barancik, M; Ravingerova, T

    2016-09-19

    Quercetin, a polyphenolic compound present in various types of food, has been shown to exert beneficial effects in different cardiac as well as non-cardiac ischemia/reperfusion (I/R) models in adult animals. However, there is no evidence about the effects of quercetin on I/R injury in non-mature animals, despite the fact that efficiency of some interventions against I/R is age-dependent. This study was aimed to investigate the effects of chronic quercetin treatment on I/R injury in juvenile and adult rat hearts. Juvenile (4-week-old) as well as adult (12-week-old) rats were treated with quercetin (20 mg/kg/day) for 4 weeks, hearts were excised and exposed to 25-min global ischemia followed by 40-min reperfusion. Functional parameters of hearts and occurrence of reperfusion arrhythmias were registered to assess the cardiac function. Our results have shown that quercetin improved post-ischemic recovery of LVDP, as well as recovery of markers of contraction and relaxation, +(dP/dt)max and -(dP/dt)max, respectively, in juvenile hearts, but not in adult hearts. Quercetin had no impact on incidence as well as duration of reperfusion arrhythmias in animals of both ages. We conclude that the age of rats plays an important role in heart response to quercetin treatment in the particular dose and duration of the treatment. Therefore, the age of the treated subjects should be taken into consideration when choosing the dose of quercetin and duration of its application in prevention and/or treatment of cardiovascular diseases.

  6. Direct vascular actions of quercetin in aorta from renal hypertensive rats

    PubMed Central

    Choi, Seok; Ryu, Kwon Ho; Park, Sang Hag; Jun, Jae Yeoul; Shin, Byung Chul; Chung, Jong Hoon; Yeum, Cheol Ho

    2016-01-01

    Background Chronic treatment with the dietary flavonoid quercetin is known to lower blood pressure and restore endothelial dysfunction in animal models of hypertension. This study investigated the direct effects of quercetin on vascular response in chronic 2-kidney, 1-clip (2K1C) renal hypertensive rats. The effects of antioxidant vitamin ascorbic acid on the vasoreactivity were also examined. Methods 2K1C renal hypertension was induced by clipping the left renal artery; age-matched rats that received sham treatment served as controls. Thoracic aortae were mounted in tissue baths for the measurement of isometric tension. Results Relaxant responses to acetylcholine were significantly attenuated in 2K1C rats in comparison with sham rats. Quercetin or ascorbic acid augmented acetylcholine-induced relaxation in 2K1C rats, whereas no significant differences were noted in sham rats. The relaxation response to sodium nitroprusside was comparable between 2K1C and sham rats, and sodium nitroprusside–induced relaxation was not altered by quercetin or ascorbic acid in either group. The contractile response to phenylephrine was significantly enhanced in 2K1C rats compared with sham rats. Phenylephrine-induced contraction was inhibited by pretreatment with quercetin or ascorbic acid in 2K1C rats, whereas neither chemical affected responses in sham rats. Nw-nitro-L-arginine methyl ester markedly augmented the contractile response to phenylephrine in sham rats, whereas no significant differences were observed in 2K1C rats. Quercetin or ascorbic acid did not affect phenylephrine-induced contraction in the presence of Nw-nitro-L-arginine methyl ester in either 2K1C or sham rats. Conclusion Acute exposure to quercetin appears to improve endothelium-dependent relaxation and inhibit the contractile response, similar to the effect of ascorbic acid in 2K1C hypertension. These results partially explain the vascular beneficial effects of quercetin in renal hypertension. PMID:27069853

  7. Cardioprotective effects of quercetin against ischemia-reperfusion injury are age-dependent.

    PubMed

    Bartekova, M; Radosinska, J; Pancza, D; Barancik, M; Ravingerova, T

    2016-09-19

    Quercetin, a polyphenolic compound present in various types of food, has been shown to exert beneficial effects in different cardiac as well as non-cardiac ischemia/reperfusion (I/R) models in adult animals. However, there is no evidence about the effects of quercetin on I/R injury in non-mature animals, despite the fact that efficiency of some interventions against I/R is age-dependent. This study was aimed to investigate the effects of chronic quercetin treatment on I/R injury in juvenile and adult rat hearts. Juvenile (4-week-old) as well as adult (12-week-old) rats were treated with quercetin (20 mg/kg/day) for 4 weeks, hearts were excised and exposed to 25-min global ischemia followed by 40-min reperfusion. Functional parameters of hearts and occurrence of reperfusion arrhythmias were registered to assess the cardiac function. Our results have shown that quercetin improved post-ischemic recovery of LVDP, as well as recovery of markers of contraction and relaxation, +(dP/dt)max and -(dP/dt)max, respectively, in juvenile hearts, but not in adult hearts. Quercetin had no impact on incidence as well as duration of reperfusion arrhythmias in animals of both ages. We conclude that the age of rats plays an important role in heart response to quercetin treatment in the particular dose and duration of the treatment. Therefore, the age of the treated subjects should be taken into consideration when choosing the dose of quercetin and duration of its application in prevention and/or treatment of cardiovascular diseases. PMID:27643931

  8. Effect of quercetin and its metabolite on caveolin-1 expression induced by oxidized LDL and lysophosphatidylcholine in endothelial cells

    PubMed Central

    Kamada, Chiemi; Mukai, Rie; Kondo, Akari; Sato, Shinya; Terao, Junji

    2016-01-01

    Oxidized low-density lipoprotein contributes to atherosclerotic plaque formation, and quercetin is expected to exert anti-atherosclerotic effects. We previously reported accumulation of conjugated quercetin metabolites in the aorta of rabbits fed high-cholesterol diets with quercetin glucosides, resulting in attenuation of lipid peroxidation and inhibition of lipid accumulation. Caveolin-1, a major structural protein of caveolae in vascular endothelial cells, plays a role in atherosclerosis development. Here we investigated effects of oxidized low-density lipoprotein, quercetin and its metabolite, quercetin 3-O-β-glucuronide, on caveolin-1 expression. Oxidized low-density lipoprotein significantly upregulated caveolin-1 mRNA expression. An oxidized low-density lipoprotein component, lysophosphatidylcholine, also induced expression of both caveolin-1 mRNA and protein. However, lysophosphatidylcholine did not affect the location of caveolin-1 proteins within caveolae structures. Co-treatment with quercetin or quercetin 3-O-β-glucuronide inhibited lysophosphatidylcholine-induced caveolin-1 expression. Quercetin and quercetin 3-O-β-glucuronide also suppressed expression of adhesion molecules induced by oxidized low-density lipoprotein and lysophosphatidylcholine. These results strongly suggest lysophosphatidylcholine derived from oxidized low-density lipoprotein contributes to atherosclerotic events by upregulating caveolin-1 expression, resulting in induction of adhesion molecules. Quercetin metabolites are likely to exert an anti-atherosclerotic effect by attenuating caveolin-1 expression in endothelial cells. PMID:27257344

  9. Ameliorative effect of quercetin against arsenic-induced sperm DNA damage and daily sperm production in adult male rats.

    PubMed

    Jahan, Sarwat; Rehman, Saima; Ullah, Hizb; Munawar, Asma; Ain, Qurat Ul; Iqbal, Tariq

    2016-01-01

    In this study, the protective effect of quercetin was evaluated against arsenic induced reproductive ailments in male rats. For this purpose, male rats (n = 5/group) weighing 180-250 g were used. First group served as control, second group received arsenic (50 ppm) in drinking water. Third group was treated with quercetin (50 mg/kg) alone, while fourth group received arsenic + quercetin. All treatments were carried out for 49 days. After treatment, animals were killed by decapitation; testis and epididymis were dissected out. Right epididymis was minced immediately for comet assay, while left epididymis was processed for histology. Similarly, right testis was homogenized for estimation of daily sperm production (DSP) and detection of metal concentration. The results of our research revealed that arsenic treatment did not cause any significant change in body weight and testicular volume. Quercetin treatment significantly prevented tissue deposition of arsenic within the testis. Arsenic treatment caused a significant reduction in DSP, however, in the arsenic + quercetin-treated group and quercetin alone-treated group, DSP was significantly high as compared to the arsenic-treated group. Histological study of epididymis showed empty lumen in arsenic-treated group while in arsenic + quercetin-treated group and quercetin alone-treated group, lumen were filled with sperm and were comparable to control. Sperm DNA damage, induced by arsenic, was significantly reversed toward control levels by supplementation of quercetin. These results suggest that quercetin not only prevents deposition of arsenic in tissues, but can also protect the sperm DNA damage.

  10. Quercetin and vitamin E attenuate Bonny Light crude oil-induced alterations in testicular apoptosis, stress proteins and steroidogenic acute regulatory protein in Wistar rats.

    PubMed

    Ebokaiwe, Azubuike P; Mathur, Premendu P; Farombi, Ebenezer O

    2016-10-01

    Studies have shown the reproductive effects of Bonny Light crude oil (BLCO) via the mechanism of oxidative stress and testicular apoptosis. We investigated the protective role of quercetin and vitamin E on BLCO-induced testicular apoptosis. Experimental rats were divided into four groups of four each. Animals were orally administered 2 ml/kg corn oil (control: group 1), BLCO-800 mg/kg body weight + 10 mg/kg quercetin (group 2), BLCO-800 mg/kg body weight + 50 mg/kg vitamin E (group 3) and BLCO-800 mg/kg body weight only (group 4) for 7 d. Protein levels of caspase 3, FasL, NF-kB, steroidogenic acute regulatory protein and stress response proteins were determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Immunofluorescence staining was used to quantify the expression of caspase 3, FasL and NF-kB. Apoptosis was quantified by the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay. Administration of BLCO resulted in a significant increase in the levels of stress response proteins and apoptosis-related proteins by 50% and above after 7 d following BLCO exposure and a concomitant increase in expression of caspase 3, FasL and NF-kB expression by immunofluorescence staining. Apoptosis showed a significant increase in TUNEL positive cells. Co-administration with quercetin or vitamin E reversed BLCO-induced apoptosis and levels of stress protein, relative to control. These findings suggest that quercetin and vitamin E may confer protection against BLCO-induced testicular oxidative stress-related apoptosis.

  11. Re-evaluation of the kidney tumors and renal histopathology occurring in a 2-year rat carcinogenicity bioassay of quercetin.

    PubMed

    Hard, Gordon C; Seely, John Curtis; Betz, Laura J; Hayashi, Shim-Mo

    2007-04-01

    Renal histopathology in the most recent 2-year carcinogenicity bioassay of quercetin, in Fischer 344 rats, was re-evaluated in an attempt to determine a mode of action underlying a small increase in renal tubule tumors reported in the males (). The re-evaluation confirmed the reported increase in renal tumors in mid- and high-dose males, including a single carcinoma in a high-dose male, as well as an exacerbation of spontaneous, chronic progressive nephropathy (CPN) in male rats only. The re-evaluation also showed that there were no cellular alterations in the kidney indicative of chemical toxicity at 6 months, 15 months, or 2 years. The evidence linked the occurrence of the predominant basophilic adenomas and foci of atypical tubule hyperplasia (ATH) with the exacerbation of CPN to advanced grades of severity, supporting a mode of action involving quercetin interaction with CPN. This mode of action represents a secondary mechanism for renal tumor development, with no relevance for extrapolation to humans. In addition, the single carcinoma present in the high-dose males, along with 4 other lesions ranging from ATH to adenoma in male and female groups, were considered to have a unique phenotype associated previously with neoplasms of spontaneous and familial origin.

  12. Experimental evidence and molecular modeling of the interaction between hRSV-NS1 and quercetin.

    PubMed

    Gomes, Deriane Elias; Caruso, Ícaro Putinhon; de Araujo, Gabriela Campos; de Lourenço, Isabella Otenio; de Melo, Fernando Alves; Cornélio, Marinônio Lopes; Fossey, Marcelo Andrés; de Souza, Fátima Pereira

    2016-04-01

    Human Respiratory Syncytial Virus is one of the major causes of acute respiratory infections in children, causing bronchiolitis and pneumonia. Non-Structural Protein 1 (NS1) is involved in immune system evasion, a process that contributes to the success of hRSV replication. This protein can act by inhibiting or neutralizing several steps of interferon pathway, as well as by silencing the hRSV ribonucleoproteic complex. There is evidence that quercetin can reduce the infection and/or replication of several viruses, including RSV. The aims of this study include the expression and purification of the NS1 protein besides experimental and computational assays of the NS1-quercetin interaction. CD analysis showed that NS1 secondary structure composition is 30% alpha-helix, 21% beta-sheet, 23% turn and 26% random coils. The melting temperature obtained through DSC analysis was around 56°C. FRET analysis showed a distance of approximately 19Å between the NS1 and quercetin. Fluorescence titration results showed that the dissociation constant of the NS1-quercetin interaction was around 10(-6)M. In thermodynamic analysis, the enthalpy and entropy balanced forces indicated that the NS1-quercetin interaction presented both hydrophobic and electrostatic contributions. The computational results from the molecular modeling for NS1 structure and molecular docking regarding its interaction with quercetin corroborate the experimental data.

  13. Inhibition of hepatitis B virus replication by quercetin in human hepatoma cell lines.

    PubMed

    Cheng, Zhikui; Sun, Ge; Guo, Wei; Huang, Yayun; Sun, Weihua; Zhao, Fei; Hu, Kanghong

    2015-08-01

    Hepatitis B virus (HBV) infection is one of the most serious and prevalent viral diseases in the world. Although several anti-HBV drugs have been used clinically, their side and adverse effects limit treatment efficacy. Therefore, it is necessary to identify novel potential anti-HBV agents. The flavonol quercetin has shown activity against some retroviruses, but its effect on HBV remains unclear. In the present study, quercetin was incubated with HepG2.2.15 cells, as well as HuH-7 cells transfected with an HBV plasmid. Quercetin was shown to significantly reduce Hepatitis B surface antigen (HBsAg) and Hepatitis B e antigen (HBeAg), secretion and HBV genomic DNA levels in both cell lines. In addition, co-incubation with lamivudine (3TC), entecavir (ETV), or adefovir (Ade) further enhanced the quercetin-induced inhibition of HBV replication. This inhibition was partially associated with decreased heat shock proteins and HBV transcription levels. The results indicate that quercetin inhibited HBV antigen secretion and genome replication in human hepatoma cell lines, which suggests that quercetin may be a potentially effective anti-HBV agent.

  14. Bioconversion of quercetin and rutin and the cytotoxicity activities of the transformed products.

    PubMed

    Araújo, Kelly Carolina Frauzino; de M B Costa, Eula Maria; Pazini, Francine; Valadares, Marize Campos; de Oliveira, Valéria

    2013-01-01

    Quercetin and rutin are well-know flavonoids. In spite of this, the comprehension of their metabolism is still incomplete. In this work, the cytotoxic activity of quercetin and rutin and its metabolites produced by metabolism of filamentous fungi was investigated. Flavonoids metabolism was monitored by HPLC and LC-MS. Both flavonoids were extensively metabolized. Quercetin was converted into metabolite methylquercetin (2) and quercetin glucuronide (3) and rutin into metabolite rutin sulphate (5), methylrutin (6) and rutin glucuronide (7). Cytotoxic effects of rutin, quercetin and its metabolites were measured by MTT tetrazolium reduction test and the trypan blue exclusion assay on HL-60 leukemic cells. The results showed similar concentration-dependent cytotoxic effect for rutin and rutin sulphate (5), while no cytotoxic effect was detected with the metabolites 6 and 7. In relation to the quercetin and its metabolites the results showed that all compounds have a similar concentration-dependent inhibitory effect on HL-60 cells. These findings corroborate the literature, showing that bioconversion is a useful strategy for production of biological active metabolites.

  15. Quercetin suppresses cellular migration and invasion in human head and neck squamous cell carcinoma (HNSCC).

    PubMed

    Chan, Chien-Yi; Lien, Chia-Hsien; Lee, Ming-Fen; Huang, Chun-Yin

    2016-06-01

    Head and neck squamous cell carcinoma (HNSCC) with aberrant epidermal growth factor receptor (EGFR) signaling is often associated with a poor prognosis and a low survival rate. Hence, efficient inhibition of the EGFR signaling-mediated malignancy would improve survival rate. In a previous study, we demonstrated that quercetin appears to be a potent anti-tumorigenic agent through its inhibition of the EGFR/Akt pathway in oral cancer, but its anti-metastatic potential in HNSCC remains unclear [1]. Here, we have hypothesized that quercetin might be effective in metastatic inhibition in EGFR-overexpressing HNSCC cells. Quercetin treatment with 10 μM (half concentration of IC50) suppressed cell migration and invasion in EGFR-overexpressing HSC-3 and FaDu HNSCC cells. Quercetin also inhibited the colony growth of HSC-3 cells embedded in a Matrigel matrix. Among matrix metalloproteinases (MMPs), the secreted gelatinases MMP-2 and MMP-9 are responsible for the degradation of gelatin in the extracellular matrix and type IV collagen in the basement membrane; and this degradation event is crucial for the migration from the origin and the invasion into the bone in HNSCC. Quercetin (10 μM) treatment also suppressed the expression and proteolytic activity of MMP-2 and MMP-9. Taken together, our data indicate that quercetin is an effective anti-cancer agent against MMP-2- and MMP-9-mediated metastasis in EGFR-overexpressing HNSCC. PMID:27510965

  16. Development of an antioxidant biomaterial by promoting the deglycosylation of rutin to isoquercetin and quercetin.

    PubMed

    Cruz-Zúñiga, Johana M; Soto-Valdez, Herlinda; Peralta, Elizabeth; Mendoza-Wilson, Ana María; Robles-Burgueño, M Refugio; Auras, Rafael; Gámez-Meza, Nohemí

    2016-08-01

    Quercetin-3-O-rutinoside (rutin), quercetin-3-O-glucoside (isoquercetin) and quercetin have shown antioxidant, cytoprotective, vasoprotective, antiproliferative and antiinflammatory properties. The aim of this work was to determine the conversion of rutin to isoquercetin and quercetin during the production of poly(l-lactic acid) films with potential to deliver these flavonoids toward tissues, pharmaceuticals or food matrices. Three poly(l-lactic acid) formulations with 17.7, 39.6 and 39.1mg/g of rutin were prepared by the extrusion process. Processing temperatures (130-165°C) promoted the deglycosylation of rutin to produce isoquercetin and subsequently quercetin, identified by high performance liquid chromatography coupled to mass spectrometry. The effect of the process on the antioxidant activity of the films was determined by measuring the capacity to scavenge 2,2 diphenyl-1-picrylhydrazyl radicals. The material with the highest proportion of quercetin showed the highest antioxidant activity which could be used to produce delivering devices of the flavonoids to tissues, pharmaceuticals or food matrices. PMID:26988520

  17. Potential of Excipient Emulsions for Improving Quercetin Bioaccessibility and Antioxidant Activity: An in Vitro Study.

    PubMed

    Chen, Xing; Zou, Liqiang; Liu, Wei; McClements, David Julian

    2016-05-11

    The potential for excipient emulsions to enhance the bioaccessibility and antioxidant activity of quercetin was determined in this study. Oil-in-water excipient emulsions containing two levels (4 or 10%) of small lipid droplets (d < 250 nm) were prepared from a long-chain triglyceride (corn oil). The solubilization of quercetin by the excipient emulsions was faster than by bulk corn oil or bulk water, and the solubilization rate was higher at 100 °C than at 30 °C. The bioaccessibility of quercetin samples was determined using an in vitro gastrointestinal model, and the bioactivity of quercetin was determined using a rat feeding study. The excipient emulsions were more effective at enhancing quercetin bioaccessibility and rat plasma antioxidant activity than either bulk oil or bulk water. This effect was attributed to the rapid digestion of the long chain triglycerides when they were in an emulsified form, which led to the rapid production of mixed micelles capable of solubilizing, protecting, and transporting quercetin.

  18. Cardioprotective Effects of Quercetin in Cardiomyocyte under Ischemia/Reperfusion Injury

    PubMed Central

    Chen, Yi-Wen; Chou, Hsiu-Chuan; Lin, Szu-Ting; Chen, You-Hsuan; Chang, Yu-Jung; Chen, Linyi; Chan, Hong-Lin

    2013-01-01

    Quercetin, a polyphenolic compound existing in many vegetables, fruits, has antiinflammatory, antiproliferation, and antioxidant effect on mammalian cells. Quercetin was evaluated for protecting cardiomyocytes from ischemia/reperfusion injury, but its protective mechanism remains unclear in the current study. The cardioprotective effects of quercetin are achieved by reducing the activity of Src kinase, signal transducer and activator of transcription 3 (STAT3), caspase 9, Bax, intracellular reactive oxygen species production, and inflammatory factor and inducible MnSOD expression. Fluorescence two-dimensional differential gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) can reveal the differentially expressed proteins of H9C2 cells treated with H2O2 or quercetin. Although 17 identified proteins were altered in H2O2-induced cells, these proteins such as alpha-soluble NSF attachment protein (α-SNAP), Ena/VASP-like protein (Evl), and isopentenyl-diphosphate delta-isomerase 1 (Idi-1) were reverted by pretreatment with quercetin, which correlates with kinase activation, DNA repair, lipid, and protein metabolism. Quercetin dephosphorylates Src kinase in H2O2-induced H9C2 cells and likely blocks the H2O2-induced inflammatory response through STAT3 kinase modulation. This probably contributes to prevent ischemia/reperfusion injury in cardiomyocytes. PMID:23573126

  19. UHPLC-(ESI)QTOF MS/MS profiling of quercetin metabolites in human plasma postconsumption of applesauce enriched with apple peel and onion.

    PubMed

    Lee, Jihyun; Ebeler, Susan E; Zweigenbaum, Jerry A; Mitchell, Alyson E

    2012-08-29

    An ultrahigh pressure liquid chromatography accurate mass quadrupole time-of-flight mass spectrometry with electrospray ionization (UHPLC-(ESI)QTOF MS/MS) method was developed for measuring individual quercetin metabolites in human plasma with high sensitivity and high selectivity. Quercetin (3,3',4',5,7-pentahydroxyflavone) occurs as glycosides in foods. The composition of glycosides is species and cultivar specific. In humans, quercetin undergoes extensive biotransformation, resulting in a range of metabolites. The bioactivity of quercetin metabolites will depend on the type and position of the conjugates. Herein, individual quercetin metabolites (i.e., sulfate, glucuronide or methyl conjugates) were identified by accurate mass MS in human plasma (females = 8 and males = 8) over 24 h after consumption of applesauce enriched with either micronized apple peel (AP) or onion powder (OP). The AP and OP contained ~180 μmol of quercetin glycosides. The relative amounts of quercetin metabolites were quantified in plasma. The complement of identified quercetin metabolites was similar after consumption of AP and OP. Primary metabolites included the following: quercetin sulfate, quercetin glucuronide, and quercetin diglucuronide. A quercetin glutathione adduct was identified in negative ion mode but not apparent in positive ion mode. The pharmacokinetic parameters for AUC0-24 h and Cmax were significantly different for AP and OP. For example, consumption of the AP resulted in Cmax of quercetin sulfate, 4.6 ng/mL; quercetin glucuronide, 15.5 ng/mL; quercetin diglucuronide, 9.3 ng/mL; quercetin glucuronide sulfate, 1.3 ng/mL; methyl quercetin glucuronide, 7.5 ng/mL; and methyl quercetin diglucuronide, 3.6 ng/mL, whereas the OP resulted in Cmax of quercetin sulfate, 37.3 ng/mL; quercetin glucuronide, 212.8 ng/mL; quercetin diglucuronide, 168.8 ng/mL; quercetin glucuronide sulfate, 43.0 ng/mL; methyl quercetin glucuronide, 90.1 ng/mL; methyl quercetin diglucuronide, 65.4 ng

  20. Thermal transient anemometer

    DOEpatents

    Bailey, James L.; Vresk, Josip

    1989-01-01

    A thermal transient anemometer having a thermocouple probe which is utilized to measure the change in temperature over a period of time to provide a measure of fluid flow velocity. The thermocouple probe is located in the fluid flow path and pulsed to heat or cool the probe. The cooling of the heated probe or the heating of the cooled probe from the fluid flow over a period of time is measured to determine the fluid flow velocity. The probe is desired to be locally heated near the tip to increase the efficiency of devices incorporating the probe.

  1. Thermal transient anemometer

    DOEpatents

    Bailey, J.L.; Vresk, J.

    1989-07-18

    A thermal transient anemometer is disclosed having a thermocouple probe which is utilized to measure the change in temperature over a period of time to provide a measure of fluid flow velocity. The thermocouple probe is located in the fluid flow path and pulsed to heat or cool the probe. The cooling of the heated probe or the heating of the cooled probe from the fluid flow over a period of time is measured to determine the fluid flow velocity. The probe is desired to be locally heated near the tip to increase the efficiency of devices incorporating the probe. 12 figs.

  2. Study on the anti-H1N1 virus effects of quercetin and oseltamivir and their mechanism related to TLR7 pathway.

    PubMed

    Chen, Chen; Jiang, Zhen-You; Yu, Bin; Wu, Xian-Lin; Dai, Cong-Qi; Zhao, Chang-Lin; Ju, Da-Hong; Chen, Xiao-Yin

    2012-01-01

    The antivirus effect of quercetin and oseltamivir on the Toll-like receptor 7 (TLR7) signaling pathway was observed when dendritic cells and macrophages were infected with H1N1. Leukomonocytes were obtained from umbilical cord blood and harvested after stimulation by recombinant human Granulocyte-Macrophage Colony-Stimulating Factor (rhGM-CSF) and recombinant human Interleukin 4 (rhIL-4). Virus-infected cell model was established by human bronchial epithelial cells (16HBE) infected with H1N1. After immunological cells and virus-infected cells were co-cultured, quercetin and oseltamivir were also added into the medium as a treatment intervention. Then the immunological cells were collected for Real Time PCR (RT-PCR) and Western blot to determine the expression levels of genes related to TLR7 pathway. Viral infection led to cell death and increased the gene expression levels of TLR7 signal pathway. Quercetin and oseltamivir increased cell viability and reduced the expression levels of TLR7 signal pathway.

  3. A throat-bypass stability-bleed system using relief valves to increase the transient stability of a mixed-compression inlet. [YF-12 aircraft inlet tests in the Lewis 10 by 10 ft supersonic wind tunnel

    NASA Technical Reports Server (NTRS)

    Neiner, G. H.; Dustin, M. O.; Cole, G. L.

    1979-01-01

    A stability-bleed system was installed in a YF-12 flight inlet that was subjected to internal and external airflow disturbances in the NASA Lewis 10 by 10 foot supersonic wind tunnel. The purpose of the system is to allow higher inlet performance while maintaining a substantial tolerance (without unstart) to internal and external disturbances. At Mach numbers of 2.47 and 2.76, the inlet tolerance to decreases in diffuser-exit corrected airflow was increased by approximately 10 percent of the operating-point airflow. The stability-bleed system complemented the terminal-shock-control system of the inlet and did not show interaction problems. For disturbances which caused a combined decrease in Mach number and increase in angle of attack, the system with valves operative kept the inlet started 4 to 28 times longer than with the valves inoperative. Hence, the stability system provides additional time for the inlet control system to react and prevent unstart. This was observed for initial Mach numbers of 2.55 and 2.68. For slow increase in angle of attack at Mach 2.47 and 2.76, the system kept the inlet started beyond the steady-state unstart angle. However, the maximum transient angles of attack without unstart could not be determined because wind-tunnel mechanical-stop limits for angle of attack were reached.

  4. Synthesis and Antiviral Activity of Quercetin Brominated Derivatives.

    PubMed

    Karimova, Elza; Baltina, Lidia; Spirikhin, Leonid; Gabbasov, Tagir; Orshanskaya, Yana; Zarubaev, Vladimir

    2015-09-01

    Reaction of quercetin (QR) (1) with bromine under various conditions was studied. Interaction of QR with 2-3 equiv. of bromine in glacial acetic acid at 35-40°C for 2-4 h and 20-22°C for 24 h led to the formation of QR 6,8-dibromide (2) (52-54% yields, 96-98% purity by HPLC). Interaction of QR with 2-5 equiv. bromine in absolute ethanol at 0-5°C and 20-22°C for 24 h led to the formation of 3-O-ethyl-QR-2,3,6,8,5'-pentabromide (3) (95-97% purity by HPLC) the output of which depends on the quantity of bromine. It was shown in MDCK cell culture that compound 2 exhibits a moderate inhibitory activity against pandemic influenza virus A/H1N1/pdm09 (EC50 6.0 µg/mL, CTD50 97.7 µg/mL, SI 16). Compound 3 was inactive.

  5. Enhanced electrochemical detection of quercetin by Natural Deep Eutectic Solvents.

    PubMed

    Gomez, Federico José Vicente; Espino, Magdalena; de Los Angeles Fernandez, María; Raba, Julio; Silva, María Fernanda

    2016-09-14

    New trends in analytical chemistry encourage the development of smart techniques and methods aligned with Green Chemistry. In this sense, Natural Deep Eutectic Solvents represents an excellent opportunity as a new generation of green solvents. In this work a new application for them has been proposed and demonstrated. These solvents were synthesized by combinations of inexpensive and natural components like, Glucose, Fructose, Citric acid and Lactic acid. The different natural solvents were easily prepared and added to buffer solution in different concentrations, allowing the enhancement of electrochemical detection of an important representative antioxidant like quercetin (QR) with improved signal up to 380%. QR is a ubiquitous flavonoid widespread in plants and food of plant origin. The proposed method using phosphate buffer with a eutectic mixture of Citric acid, Glucose and water in combination with carbon screen printed electrodes exhibited a good analytical performance. Detection and quantification limits were of 7.97 and 26.3 nM respectively; and repeatability with %RSDs of 1.41 and 7.49 for peak potential and intensity respectively. In addition, it has proved to be faster, greener and cheaper than other sensors and chromatographic methods available with the additional advantage of being completely portable. Furthermore, the obtained results demonstrated that the proposed method is able for the determination of QR in complex food samples.

  6. Design and characterization of protein-quercetin bioactive nanoparticles

    PubMed Central

    2011-01-01

    Background The synthesis of bioactive nanoparticles with precise molecular level control is a major challenge in bionanotechnology. Understanding the nature of the interactions between the active components and transport biomaterials is thus essential for the rational formulation of bio-nanocarriers. The current study presents a single molecule of bovine serum albumin (BSA), lysozyme (Lys), or myoglobin (Mb) used to load hydrophobic drugs such as quercetin (Q) and other flavonoids. Results Induced by dimethyl sulfoxide (DMSO), BSA, Lys, and Mb formed spherical nanocarriers with sizes less than 70 nm. After loading Q, the size was further reduced by 30%. The adsorption of Q on protein is mainly hydrophobic, and is related to the synergy of Trp residues with the molecular environment of the proteins. Seven Q molecules could be entrapped by one Lys molecule, 9 by one Mb, and 11 by one BSA. The controlled releasing measurements indicate that these bioactive nanoparticles have long-term antioxidant protection effects on the activity of Q in both acidic and neutral conditions. The antioxidant activity evaluation indicates that the activity of Q is not hindered by the formation of protein nanoparticles. Other flavonoids, such as kaempferol and rutin, were also investigated. Conclusions BSA exhibits the most remarkable abilities of loading, controlled release, and antioxidant protection of active drugs, indicating that such type of bionanoparticles is very promising in the field of bionanotechnology. PMID:21586116

  7. Enhanced electrochemical detection of quercetin by Natural Deep Eutectic Solvents.

    PubMed

    Gomez, Federico José Vicente; Espino, Magdalena; de Los Angeles Fernandez, María; Raba, Julio; Silva, María Fernanda

    2016-09-14

    New trends in analytical chemistry encourage the development of smart techniques and methods aligned with Green Chemistry. In this sense, Natural Deep Eutectic Solvents represents an excellent opportunity as a new generation of green solvents. In this work a new application for them has been proposed and demonstrated. These solvents were synthesized by combinations of inexpensive and natural components like, Glucose, Fructose, Citric acid and Lactic acid. The different natural solvents were easily prepared and added to buffer solution in different concentrations, allowing the enhancement of electrochemical detection of an important representative antioxidant like quercetin (QR) with improved signal up to 380%. QR is a ubiquitous flavonoid widespread in plants and food of plant origin. The proposed method using phosphate buffer with a eutectic mixture of Citric acid, Glucose and water in combination with carbon screen printed electrodes exhibited a good analytical performance. Detection and quantification limits were of 7.97 and 26.3 nM respectively; and repeatability with %RSDs of 1.41 and 7.49 for peak potential and intensity respectively. In addition, it has proved to be faster, greener and cheaper than other sensors and chromatographic methods available with the additional advantage of being completely portable. Furthermore, the obtained results demonstrated that the proposed method is able for the determination of QR in complex food samples. PMID:27566343

  8. Pharmacokinetics of quercetin absorption from apples and onions in healthy humans.

    PubMed

    Lee, Jihyun; Mitchell, Alyson E

    2012-04-18

    A high-throughput method for the extraction and analysis of quercetin in human plasma using 96-well SPE and LC-(ESI)MS/MS (7 min/run) is described. Quercetin exists as a range of glycosides in foods. The dominant types of quercetin glycosides vary depending on genetics (i.e., species and cultivar). Dietary sources include onions and apples (i.e., the peel). Herein the quercetin glycoside composition was determined in a composite standard of dried apple peel and in onion powder. The predominant forms of quercetin in apple peel include quercetin O-arabinoside, 3-O-galactoside, 3-O-glucoside, and 3-O-rhamnoside. In the onion powder, quercetin occurred as the quercetin 3,4'-O-glucoside and 4'-O-glucoside. Pharmacokinetics relating to absorption (C(max), t(max), and AUC(0-24 h)) and elimination (k(el) and t(1/2)) were compared after the consumption of apple peel powder (AP), onion powder (OP), or a mixture of the apple peel and onion powder enriched applesauce (MP) by healthy volunteers (eight females and eight males). The enriched applesauce delivered ∼100 mg of quercetin aglycone equivalents. Consumption of the OP resulted in C(max) = 273.2 ± 93.7 ng/mL, t(max) = 2.0 ± 1.7 h, and t(1/2) = 14.8 ± 4.8 h, whereas the AP resulted in C(max) = 63.8 ± 22.4 ng/mL, t(max) = 2.9 ± 2.0 h, and t(1/2) = 65.4 ± 80.0 h. The MP resulted in an intermediate response with C(max) = 136.5 ± 45.8 ng/mL, t(max) = 2.4 ± 1.5 h, and t(1/2) = 18.7 ± 6.8 h. Consumption of the OP led to faster absorption, higher concentration, and greater bioavailability as compared to the AP. No significant gender-related differences were observed in the absorption of quercetin, whereas significant gender-related differences in the elimination half-time (t(1/2)) were observed. PMID:22439822

  9. Transient tachypnea - newborn

    MedlinePlus

    TTN; Wet lungs - newborns; Retained fetal lung fluid; Transient RDS; Prolonged transition; Neonatal - transient tachypnea ... As the baby grows in the womb, the lungs make a special fluid. This fluid fills the ...

  10. Influence of the metabolic profile on the in vivo antioxidant activity of quercetin under a low dosage oral regimen in rats

    PubMed Central

    Santos, M R; Rodríguez-Gómez, M J; Justino, G C; Charro, N; Florencio, M H; Mira, L

    2008-01-01

    Background and purpose Flavonoids are known to possess a broad set of pharmacological effects, some of which have been attributed to their antioxidant properties and, more recently, to cell signalling modulation. Nevertheless, flavonoids are extensively metabolized and their metabolites are the potential bioactive forms in vivo. Therefore, a first and crucial step to understand the mechanisms underlying potential health benefits of flavonoids is knowledge of their metabolites and their biological activities. Experimental approach To approximate a human dietary pattern of intake of flavonoids, regular rat chow was supplemented with 0.02% quercetin and fed to Sprague–Dawley rats over 3 weeks. Plasma samples were analysed by HPLC and electrospray tandem mass spectrometry, and plasma antioxidant capacity was measured by the 2,2′-azino-bis(3-ethylbenzothiazoline sulphonate) assay. Key results Major metabolites were 3′-methylquercetin (isorhamnetin) glucuronide sulphate conjugates, the most plausible conjugation positions being at the 3-, 5- and 7-hydroxyl positions. Isorhamnetin conjugates are methylated at the 3′-OH position, which decreases the high antioxidant activity of quercetin and its metabolites and their contribution to plasma antioxidant potential. Conclusions and implications This metabolic pattern differs from that observed after a single high-dose administration, where the major metabolites were quercetin conjugates at 5- and 7-hydroxyl positions and a significantly increased plasma antioxidant activity was observed. These data show altogether that the different metabolic patterns obtained under a prolonged low-dosage regimen or after a single high dose, crucially affected the antioxidant potential of plasma in treated animals. Our data also allow for the establishment of structure–antioxidant activity relationships for quercetin metabolites. PMID:18311191

  11. Differential responses of skin cancer-chemopreventive agents silibinin, quercetin, and epigallocatechin 3-gallate on mitogenic signaling and cell cycle regulators in human epidermoid carcinoma A431 cells.

    PubMed

    Bhatia, N; Agarwal, C; Agarwal, R

    2001-01-01

    Silibinin, quercetin, and epigallocatechin 3-gallate (EGCG) have been shown to be skin cancer-preventive agents, albeit by several different mechanisms. Here, we assessed whether these agents show their cancer-preventive potential by a differential effect on mitogenic signaling molecules and cell cycle regulators. Treatment of human epidermoid carcinoma A431 cells with these agents inhibited the activation of the epidermal growth factor receptor and the downstream adapter protein Shc, but only silibinin showed a marked inhibition of mitogen-activated protein kinase-extracellular signal-regulated kinase-1 and -2 activation. In terms of cell cycle regulators, silibinin treatment showed an induction of Cip1/p21 and Kip1/p27 together with a significant decrease in cyclin-dependent kinase (CDK)-4, CDK2, and cyclin D1. Quercetin treatment, however, resulted in a moderate increase in Cip1/p21 with no change in Kip1/p27 and a decrease in CDK4 and cyclin D1. EGCG treatment also led to an induction of Cip1/p21 but no change in Kip1/27, CDK2, and cyclin D1 and a decrease in CDK4 only at low doses. Treatment of cells with these agents resulted in a strong dose- and time-dependent cell growth inhibition. A high dose of silibinin and low and high doses of quercetin and EGCG also led to cell death by apoptosis, suggesting that a lack of their inhibitory effect on mitogen-activated protein kinase-extracellular signal-regulated kinase-1 and -2 activation possibly "turns on" an apoptotic cell death response associated with their cancer-preventive and anticarcinogenic effects. Together, these results suggest that silibinin, quercetin, and EGCG exert their cancer-preventive effects by differential responses on mitogenic signaling and cell cycle regulators.

  12. Quercetin effectively quells peanut-induced anaphylactic reactions in the peanut sensitized rats.

    PubMed

    Shishehbor, Farideh; Behroo, Lotfollah; Ghafouriyan Broujerdnia, Mehri; Namjoyan, Forough; Latifi, Seiyed-Mahmoud

    2010-03-01

    Peanut allergy is the major leading cause of fatal or life-threatening anaphylactic reactions to foods. At present, there is no remedy for this condition. The applied pharmaceutical cares are merely palliative, while their deleterious side effects have already been established. Hence, many sufferers search for complementary and alternative medicines. A versatile-, "flavonol" subgroup-member of the flavonoid family, quercetin, is of paramount interest to investigators. In this study the effects of quercetin on peanut-induced anaphylactic reactions were investigated in a rat model of peanut allergy. Wistar rats were sensitized with crude peanut extract in the presence of Cholera toxin and Aluminium hydroxide. Sensitized rats were then allotted into three groups; Positive control, Quercetin-treatment and Sham, (n=7, each). Naive rats (n=7) served as negative controls. One week post-sensitization period, the rats in treatment group were treated with quercetin at a dose of 50 mg/kg(Body Weight)/mL Di-methyl-sulfoxide 5%/rat, over a period of four weeks. Subsequently, rats were challenged, and anaphylactic reaction parameters including variations in plasma histamine levels, vascular permeability, systemic anaphylaxis scores, and total serum Immunoglobulin E levels were measured. After daily-gavaging for four weeks, quercetin completely abrogated peanut-induced anaphylactic reactions following challenges, so that the mean of plasma histamine levels in the quercetin-treated rats, were lower significantly (p=0.004) as compared with positive control group. Our findings suggest that the flavonoid quercetin is potent enough to suppress the on-going Immunoglobulin E responses against peanut proteins, and can be propounded as an alternative medicine to protect against Immunoglobulin E-mediated food allergies.

  13. Protective effect of quercetin on skeletal and neural tube teratogenicity induced by cyclophosphamide in rat fetuses.

    PubMed

    Khaksary Mahabady, Mahmood; Gholami, Mohammad Reza; Najafzadeh Varzi, Hossein; Zendedel, Abolfazl; Doostizadeh, Mona

    2016-01-01

    Cyclophosphamide (CP) is a drug commonly used to treat neoplastic disease and some autoimmune diseases. It is also a well-known and well-studied teratogen causing a variety of birth defects in fetuses of pregnant women treated with the drug. There are many reports that show the adverse effects of CP can be decreased by use of antioxidant drugs. It appears that, quercetin has antioxidant effect. The aim of this study was prevention or decrease of teratogenicity of CP in fetuses of rats by quercetin. This study was performed on 35 pregnant rats divided into six groups. Control group was received normal saline (5 mL kg(-1), intraperitoneally) and 2-6 groups received a single dose of CP (15 mg kg(-1)), a single dose of quercetin (75 or 200 mg kg(-1)), CP plus quercetin (75 or 200 mg kg(-1)) intraperitoneally at 9(th) day of gestation, respectively. Fetuses were collected at 20(th) day of gestation and after determination of weight and crown rump length were stained by alizarin red - alcian blue method and skeletal system were examined by stereomicroscope. The results showed that the cleft palate, exencephaly, spina bifida and omphalocele incidence were 55.56%, 27.77%, 33.34% and 11.11%, in fetuses of rat that received only CP, respectively. However, it decreased to 16.00%, 16.00%, 16.00% and 8.00% by quercetin (75 mg kg(-1)) and so to 12.90%, 12.90%, 6.45% and 3.28% by quercetin (200 mg kg(-1)), respectively. On the basis of results, quercetin significantly can decrease teratogenicity induced by CP. PMID:27482358

  14. Protective effect of quercetin on skeletal and neural tube teratogenicity induced by cyclophosphamide in rat fetuses

    PubMed Central

    Khaksary Mahabady, Mahmood; Gholami, Mohammad Reza; Najafzadeh Varzi, Hossein; Zendedel, Abolfazl; Doostizadeh, Mona

    2016-01-01

    Cyclophosphamide (CP) is a drug commonly used to treat neoplastic disease and some autoimmune diseases. It is also a well-known and well-studied teratogen causing a variety of birth defects in fetuses of pregnant women treated with the drug. There are many reports that show the adverse effects of CP can be decreased by use of antioxidant drugs. It appears that, quercetin has antioxidant effect. The aim of this study was prevention or decrease of teratogenicity of CP in fetuses of rats by quercetin. This study was performed on 35 pregnant rats divided into six groups. Control group was received normal saline (5 mL kg-1, intraperitoneally) and 2-6 groups received a single dose of CP (15 mg kg-1), a single dose of quercetin (75 or 200 mg kg-1), CP plus quercetin (75 or 200 mg kg-1) intraperitoneally at 9th day of gestation, respectively. Fetuses were collected at 20th day of gestation and after determination of weight and crown rump length were stained by alizarin red – alcian blue method and skeletal system were examined by stereomicroscope. The results showed that the cleft palate, exencephaly, spina bifida and omphalocele incidence were 55.56%, 27.77%, 33.34% and 11.11%, in fetuses of rat that received only CP, respectively. However, it decreased to 16.00%, 16.00%, 16.00% and 8.00% by quercetin (75 mg kg-1) and so to 12.90%, 12.90%, 6.45% and 3.28% by quercetin (200 mg kg-1), respectively. On the basis of results, quercetin significantly can decrease teratogenicity induced by CP. PMID:27482358

  15. Transient drainage summary report

    SciTech Connect

    1996-09-01

    This report summarizes the history of transient drainage issues on the Uranium Mill Tailings Remedial Action (UMTRA) Project. It defines and describes the UMTRA Project disposal cell transient drainage process and chronicles UMTRA Project treatment of the transient drainage phenomenon. Section 4.0 includes a conceptual cross section of each UMTRA Project disposal site and summarizes design and construction information, the ground water protection strategy, and the potential for transient drainage.

  16. Enhanced inhibition of prostate cancer xenograft tumor growth by combining quercetin and green tea.

    PubMed

    Wang, Piwen; Vadgama, Jaydutt V; Said, Jonathan W; Magyar, Clara E; Doan, Ngan; Heber, David; Henning, Susanne M

    2014-01-01

    The chemopreventive activity of green tea (GT) is limited by the low bioavailability and extensive methylation of GT polyphenols (GTPs) in vivo. We determined whether a methylation inhibitor quercetin (Q) will enhance the chemoprevention of prostate cancer in vivo. Androgen-sensitive LAPC-4 prostate cancer cells were injected subcutaneously into severe combined immunodeficiency (SCID) mice one week before the intervention. The concentration of GTPs in brewed tea administered as drinking water was 0.07% and Q was supplemented in diet at 0.2% or 0.4%. After 6-weeks of intervention tumor growth was inhibited by 3% (0.2% Q), 15% (0.4% Q), 21% (GT), 28% (GT+0.2% Q) and 45% (GT+0.4% Q) compared to control. The concentration of non-methylated GTPs was significantly increased in tumor tissue with GT+0.4% Q treatment compared to GT alone, and was associated with a decreased protein expression of catechol-O-methyltransferase and multidrug resistance-associated protein (MRP)-1. The combination treatment was also associated with a significant increase in the inhibition of proliferation, androgen receptor and phosphatidylinositol 3-kinase/Akt signaling, and stimulation of apoptosis. The combined effect of GT+0.4% Q on tumor inhibition was further confirmed in another experiment where the intervention started prior to tumor inoculation. These results provide a novel regimen by combining GT and Q to improve chemoprevention in a non-toxic manner and warrant future studies in humans.

  17. Protection of Quercetin against Triptolide-induced apoptosis by suppressing oxidative stress in rat Leydig cells.

    PubMed

    Hu, Jie; Yu, Qinwei; Zhao, Fang; Ji, Jinzi; Jiang, Zhenzhou; Chen, Xin; Gao, Peng; Ren, Yuran; Shao, Shuai; Zhang, Luyong; Yan, Ming

    2015-10-01

    Triptolide (TP) is a diterpene triepoxide with variety biological activities, such as anti-inflammatory, anti-cancerogenic, immunomodulatory and pro-apoptotic activities. However, its clinical application was limited by potential toxicity. Quercetin (Que) is a member of flavonoids with anti-oxidant effects. In this study, we aimed to demonstrate the protective effect of Que in TP-induced oxidative stress and decrease of testosterone generation in reproductive damage. Leydig cells were treated with TP (20, 40 and 60 nM), which caused obvious oxidative stress increasing intracellular ROS, decreasing activities and expressions of GPx and SOD. Apoptosis was resulted from depolarization of mitochondrial membrane potential (ΔΨm) and release of cytochrome C (Cyt-C) showing increase of BAX/Bcl-2 ratio, caspase-3 and caspase-9. Treatment of Que (5 μM) prior to triptolide could restore all the TP-induced alteration in a certain dose range indicating that the oxidative stress might be one reason of TP-induced reproductive toxic effect. These results suggest that the compatibility with Que might reduce the TP-induced reproductive toxicity, which provide a probability to extend the usage of TP. PMID:26277538

  18. Quercetin reduces obesity-associated ATM infiltration and inflammation in mice: a mechanism including AMPKα1/SIRT1[S

    PubMed Central

    Dong, Jing; Zhang, Xian; Zhang, Lei; Bian, Hui-Xi; Xu, Na; Bao, Bin; Liu, Jian

    2014-01-01

    Adipose tissue macrophage (ATM) plays a central role in obesity-associated inflammation and insulin resistance. Quercetin, a dietary flavonoid, possesses anti-inflammation and anti-insulin resistance properties. However, it is unclear whether quercetin can alleviate high-fat diet (HFD)-induced ATM infiltration and inflammation in mice. In this study, 5-week-old C57BL/6 mice were fed low-fat diet, HFD, or HFD with 0.l% quercetin for 12 weeks, respectively. Dietary quercetin reduced HFD-induced body weight gain and improved insulin sensitivity and glucose intolerance in mice. Meanwhile, dietary quercetin enhanced glucose transporter 4 translocation and protein kinase B signal in epididymis adipose tissues (EATs), suggesting that it heightened glucose uptake in adipose tissues. Histological and real-time PCR analysis revealed that quercetin attenuated mast cell and macrophage infiltration into EATs in HFD-fed mice. Dietary quercetin also modified the phenotype ratio of M1/M2 macrophages, lowered the levels of proinflammatory cytokines, and enhanced adenosine monophosphate-activated protein kinase (AMPK) α1 phosphorylation and silent information regulator 1 (SIRT1) expression in EATs. Further, using AMPK activator 5-aminoimidazole-4-carboxamide-1-β4-ribofuranoside and inhibitor Compound C, we found that quercetin inhibited polarization and inflammation of mouse bone marrow-derived macrophages through an AMPKα1/SIRT1-mediated mechanism. In conclusion, dietary quercetin might suppress ATM infiltration and inflammation through the AMPKα1/SIRT1 pathway in HFD-fed mice PMID:24465016

  19. Protective Effects of Quercetin on Mitochondrial Biogenesis in Experimental Traumatic Brain Injury via the Nrf2 Signaling Pathway

    PubMed Central

    Li, Xiang; Wang, Handong; Gao, Yongyue; Li, Liwen; Tang, Chao; Wen, Guodao; Zhou, Yuan; Zhou, Mengliang; Mao, Lei; Fan, Youwu

    2016-01-01

    The present investigation was carried out to elucidate a possible molecular mechanism related to the protective effect of quercetin administration against oxidative stress on various mitochondrial respiratory complex subunits with special emphasis on the role of nuclear factor erythroid 2-related factor 2 (Nrf2) in mitochondrial biogenesis. Recently, quercetin has been proved to have a protective effect against mitochondria damage after traumatic brain injury (TBI). However, its precise role and underlying mechanisms in traumatic brain injury are not yet fully understood. The aim of the present study was to investigate the effect of quercetin on the potential mechanism of these effects in a weight-drop model of TBI in male mice that were treated with quercetin or vehicle via intraperitoneal injection administrated 30 min after TBI. In this experiment, ICR mice were divided into four groups: A sham group, TBI group, TBI + vehicle group, and TBI + quercetin group. Brain samples were collected 24 h later for analysis. Quercetin treatment resulted in an upregulation of Nrf2 expression and cytochrome c, malondialdehyde (MDA) and superoxide dismutase (SOD) levels were restored by quercetin treatment. Quercetin markedly promoted the translocation of Nrf2 protein from the cytoplasm to the nucleus. These observations suggest that quercetin improves mitochondrial function in TBI models, possibly by activating the Nrf2 pathway. PMID:27780244

  20. Poly(ethylene glycol) hydroxystearate-based nanosized emulsions: effect of surfactant concentration on their formation and ability to solubilize quercetin.

    PubMed

    Dora, Cristiana L; Silva, Luis F C; Putaux, Jean-Luc; Nishiyama, Yoshiharu; Pignot-Paintrand, Isabelle; Borsali, Redouane; Lemos-Senna, Elenara

    2012-04-01

    Quercetin is a natural compound that has shown several biological activities. However, it displays poor water solubility and, therefore, low bioavailability. In this study, oil-in-water nanosized emulsions were obtained by the hot solvent diffusion method, using castor oil as oily phase and poly(ethylene glycol) (660)-12-hydroxystearate (PEG 660-stearate) and lecithin as surfactants. The effect of the PEG 660-stearate concentration on the droplet size of the nanosized emulsions and on the ability of these systems to load quercetin was investigated. Dynamic light scattering (DLS), transmission electron microscopy (TEM), cryo-TEM, and small-angle X-ray scattering (SAXS) were used to characterize the systems. We have demonstrated that a critical concentration of PEG 660-stearate (2.5 wt%) was needed to obtain colloidal dispersions displaying microemulsion characteristics. This colloidal dispersion, that was not optically birefringent, was constituted by a monodisperse population of 20 nm-large droplets, and exhibited excellent stability. Besides, this system was able to solubilize five times more quercetin than nanoemulsions prepared using 0.25 wt% PEG 660-stearate. SAXS results suggest that the spherical droplets have a core-shell structure. With regard to the hot solvent diffusion method, both diffusion of the solvent towards the aqueous phase and increase of the temperature above the phase inversion temperature (PIT) of PEG 660-stearate appeared to be required for obtaining clear and isotropic colloidal dispersions.

  1. Effect of edible oils on quercetin, kaempferol and galangin transport and conjugation in the intestinal Caco-2/HT29-MTX co-culture model.

    PubMed

    Jailani, Fadhilah; Williamson, Gary

    2014-04-01

    Solubility and matrix play an important role in the gut lumen in delivering bioactive compounds to the absorptive surface of enterocytes. The purpose of this study was to determine the effect of certain commonly consumed lipids, soybean, olive and corn oil, on the transport and conjugation of flavonols (myricetin, quercetin, kaempferol and galangin) using the conjugation-competent co-cultured Caco-2/HT29-MTX intestinal cell monolayer model. To enable identification and quantification of conjugates, each flavonol was enzymatically glucuronidated or sulphated, then analysed by HPLC with triple quadrupole mass spectrometric detection. Quantification showed large differences in mass spectrometric peak area response factors between the aglycones and many of the conjugates, with galangin-sulphate for example ionising ∼15-fold better than galangin. Flavonol aglycones and conjugates were transported to the basolateral side of Caco-2/HT29-MTX co-cultures. The total amount of methyl, sulphate and glucuronide conjugates was in the order: galangin > quercetin > kaempferol > myricetin. All oils inhibited the transport and conjugation of galangin, the most hydrophobic flavonol, whereas they increased the sulphation, and to some extent glucuronidation, of quercetin and kaempferol. The results show that the lipid matrix has the potential to modify both transport and conjugation of dietary flavonols, but that the effect depends upon the structure and hydrophobicity. PMID:24525490

  2. Transient Ischemic Attack

    MedlinePlus

    Transient Ischemic Attack TIA , or transient ischemic attack, is a "mini stroke" that occurs when a blood clot blocks an artery for a short time. The only ... TIA is that with TIA the blockage is transient (temporary). TIA symptoms occur rapidly and last a ...

  3. The Rapid Transient Surveyor

    NASA Astrophysics Data System (ADS)

    Baranec, Christoph; Tonry, John; Wright, Shelley; Tully, R. Brent; Lu, Jessica R.; Takamiya, Marianne Y.; Hunter, Lisa

    2016-01-01

    The next decade of astronomy will be dominated by large area surveys (see the detailed discussion in the Astro-2010 Decadal survey and NRC's recent OIR System Report). Ground-based optical transient surveys, e.g., LSST, ZTF and ATLAS and space-based exoplanet, supernova, and lensing surveys such as TESS and WFIRST will join the Gaia all-sky astrometric survey in producing a flood of data that will enable leaps in our understanding of the universe. There is a critical need for further characterization of these discoveries through high angular resolution images, deeper images, spectra, or observations at different cadences or periods than the main surveys. Such follow-up characterization must be well matched to the particular surveys, and requires sufficient additional observing resources and time to cover the extensive number of targets.We describe plans for the Rapid Transient Surveyor (RTS), a permanently mounted, rapid-response, high-cadence facility for follow-up characterization of transient objects on the U. of Hawai'i 2.2-m telescope on Maunakea. RTS will comprise an improved robotic laser adaptive optics system, based on the prototype Robo-AO system (formerly at the Palomar 1.5-m and now at the Kitt Peak 2.2-m telescope), with simultaneous visible and near-infrared imagers as well as a near-infrared integral field spectrograph (R~100, λ = 850 - 1830 nm, 0.15″ spaxels, 8.7″×6.0″ FoV). RTS will achieve an acuity of ~0.07″ in visible wavelengths and < 0.16″ in the near infrared leading to an increase of the infrared point-source sensitivity against the sky background by a factor of ~9, crucial for efficient near-infrared spectroscopy.RTS will allow us to map the dark matter distribution in the z < 0.1 local universe with ten times better accuracy and precision than previous experiments. ATLAS will discover several thousand SNIae per year, measuring SNIa peak brightness, and decline rates, while RTS will measure reddening by dust, confirm SN type and

  4. Quercetin Impacts Expression of Metabolism- and Obesity-Associated Genes in SGBS Adipocytes.

    PubMed

    Leiherer, Andreas; Stoemmer, Kathrin; Muendlein, Axel; Saely, Christoph H; Kinz, Elena; Brandtner, Eva M; Fraunberger, Peter; Drexel, Heinz

    2016-05-12

    Obesity is characterized by the rapid expansion of visceral adipose tissue, resulting in a hypoxic environment in adipose tissue which leads to a profound change of gene expression in adipocytes. As a consequence, there is a dysregulation of metabolism and adipokine secretion in adipose tissue leading to the development of systemic inflammation and finally resulting in the onset of metabolic diseases. The flavonoid quercetin as well as other secondary plant metabolites also referred to as phytochemicals have anti-oxidant, anti-inflammatory, and anti-diabetic effects known to be protective in view of obesity-related-diseases. Nevertheless, its underlying molecular mechanism is still obscure and thus the focus of this study was to explore the influence of quercetin on human SGBS (Simpson Golabi Behmel Syndrome) adipocytes' gene expression. We revealed for the first time that quercetin significantly changed expression of adipokine (Angptl4, adipsin, irisin and PAI-1) and glycolysis-involved (ENO2, PFKP and PFKFB4) genes, and that this effect not only antagonized but in part even overcompensated the effect mediated by hypoxia in adipocytes. Thus, these results are explained by the recently proposed hypothesis that the protective effect of quercetin is not solely due to its free radical-scavenging activity but also to a direct effect on mitochondrial processes, and they demonstrate that quercetin might have the potential to counteract the development of obesity-associated complications.

  5. Structural insights into the polypharmacological activity of quercetin on serine/threonine kinases

    PubMed Central

    Baby, Bincy; Antony, Priya; Al Halabi, Walaa; Al Homedi, Zahrah; Vijayan, Ranjit

    2016-01-01

    Polypharmacology, the discovery or design of drug molecules that can simultaneously interact with multiple targets, is gaining interest in contemporary drug discovery. Serine/threonine kinases are attractive targets for therapeutic intervention in oncology due to their role in cellular phosphorylation and altered expression in cancer. Quercetin, a naturally occurring flavonoid, inhibits multiple cancer cell lines and is used as an anticancer drug in Phase I clinical trial. Quercetin glycosides have also received some attention due to their high bioavailability and activity against various diseases including cancer. However, these have been studied to a lesser extent. In this study, the structural basis of the multitarget inhibitory activity of quercetin and isoquercitrin, a glycoside derivative, on serine/threonine kinases using molecular modeling was explored. Structural analysis showed that both quercetin and isoquercitrin exhibited good binding energies and interacted with aspartate in the highly conserved Asp–Phe–Gly motif. The results indicate that isoquercitrin could be a more potent inhibitor of several members of the serine/threonine kinase family. In summary, the current structural evaluation highlights the multitarget inhibitory property of quercetin and its potential to be a chemical platform for oncological polypharmacology. PMID:27729770

  6. Quercetin Impacts Expression of Metabolism- and Obesity-Associated Genes in SGBS Adipocytes

    PubMed Central

    Leiherer, Andreas; Stoemmer, Kathrin; Muendlein, Axel; Saely, Christoph H.; Kinz, Elena; Brandtner, Eva M.; Fraunberger, Peter; Drexel, Heinz

    2016-01-01

    Obesity is characterized by the rapid expansion of visceral adipose tissue, resulting in a hypoxic environment in adipose tissue which leads to a profound change of gene expression in adipocytes. As a consequence, there is a dysregulation of metabolism and adipokine secretion in adipose tissue leading to the development of systemic inflammation and finally resulting in the onset of metabolic diseases. The flavonoid quercetin as well as other secondary plant metabolites also referred to as phytochemicals have anti-oxidant, anti-inflammatory, and anti-diabetic effects known to be protective in view of obesity-related-diseases. Nevertheless, its underlying molecular mechanism is still obscure and thus the focus of this study was to explore the influence of quercetin on human SGBS (Simpson Golabi Behmel Syndrome) adipocytes’ gene expression. We revealed for the first time that quercetin significantly changed expression of adipokine (Angptl4, adipsin, irisin and PAI-1) and glycolysis-involved (ENO2, PFKP and PFKFB4) genes, and that this effect not only antagonized but in part even overcompensated the effect mediated by hypoxia in adipocytes. Thus, these results are explained by the recently proposed hypothesis that the protective effect of quercetin is not solely due to its free radical-scavenging activity but also to a direct effect on mitochondrial processes, and they demonstrate that quercetin might have the potential to counteract the development of obesity-associated complications. PMID:27187453

  7. Evaluation of antigenotoxic effects of plant flavonoids quercetin and rutin on HepG2 cells.

    PubMed

    Barcelos, Gustavo R M; Grotto, Denise; Angeli, José Pedro F; Serpeloni, Juliana M; Rocha, Bruno A; Bastos, Jairo K; Barbosa, Fernando

    2011-09-01

    The flavonoid quercetin and its derivative rutin were investigated for genotoxicity/antigenotoxicity activity in human hepatoma HepG2 cells using the comet assay. The extract cytotoxicity was evaluated using the trypan blue exclusion dye method with quercetin and rutin concentrations ranging from 0.1 to 200.0 μg/mL of culture medium. Three minor non-cytotoxic concentrations were chosen to evaluate the genotoxicity and antigenotoxicity of the flavonoids (0.1, 1.0 and 5.0 μg/mL) through comet assay. The cultures were treated with three different concentrations of rutin or quercetin (genotoxicity) or their association with Aflatoxin B1 (AFB1), methyl methanesulfonate (MMS) or doxorubicin (DXR) (antigenotoxicity test) in three protocols: pre-treatment, simultaneous treatment and post-treatment. The cell cultures were also treated with 1% DMSO (control group), AFB1, MMS and DXR (positive-control). Statistical analyses were performed using ANOVA and Dunnett's test (p ≤ 0.05). Quercetin at concentrations higher than 10.0 μg/mL or rutin higher than 50.0 μg/mL exhibited a cytotoxic effect on the cells, showing that quercetin is more cytotoxic than rutin. Furthermore, neither compound was able to induce genotoxicity in the concentrations evaluated. On the other hand, both flavonoids reduced DNA damage induced by AFB1, MMS and DXR in all treatment protocols.

  8. Quercetin induces bladder cancer cells apoptosis by activation of AMPK signaling pathway

    PubMed Central

    Su, Qiongli; Peng, Mei; Zhang, Yuqing; Xu, Wanjun; Darko, Kwame Oteng; Tao, Ting; Huang, Yanjun; Tao, Xiaojun; Yang, Xiaoping

    2016-01-01

    Quercetin, a natural existing polyphenol compound, has shown anticancer capacity for liver, breast, nasopharyngeal and prostate carcinoma but has not been clinically approved yet. This might be due to lack of clear mechanistic picture. Bladder cancer is one of the most common cancers of the urinary tract in the world. In China, bladder cancer has the highest rate of incidence out of all malignancies of the urinary system. The anticancer application of quercetin on bladder cancer has not been investigated either. This study was aimed to examine the mechanisms of quercetin on inhibition of bladder cancer. First, two human and one murine bladder cancer cell lines were tested in vitro for inhibitory sensitivity by MTT and cologenic assays. Second, AMPK pathway including 4E-BP1 and S6K were examined by western blot. Quercetin induces apoptosis and inhibits migration. We are the first to show that quercetin displays potent inhibition on bladder cancer cells via activation of AMPK pathway. PMID:27186419

  9. CD/AuNPs/MWCNTs based electrochemical sensor for quercetin dual-signal detection.

    PubMed

    Kan, Xianwen; Zhang, Tingting; Zhong, Min; Lu, Xiaojing

    2016-03-15

    A dual-signal strategy was developed in the present work for quercetin (QR) electrochemical recognition and detection. Mercapto-β-cyclodextrin (HS-β-CD) self-assembled on gold nanoparticles and multi-walled carbon nanotubes modified electrode surface to fabricate an electrochemical sensor. Scanning electron microscope, electrochemical impedance spectroscopy, and cyclic voltammetry were employed to characterize the preparation process of the sensor. Hydroquinone (HQ) was chosen as an electrochemical marker for QR detection due to its small molecular size for the formation of inclusion with HS-β-CD. The results of UV-vis and differential pulse voltammetry demonstrate that the added QR can replace the included HQ in CD cavities, resulting in the dual-signal in electrochemical experiments composed of the decrease of oxidized current of HQ and the increase of oxidized current of QR. Compared with the sensor for QR detection in the absence of HQ, the sensor based dual-signal strategy exhibited a higher sensitivity with a wider detection range from 5.0 × 10(-9) to 7.0 × 10(-6)mol/L. With good selectivity, reproducibility, and stability, the sensor was applied for real samples detection with satisfactory results. The proposed dual-signal strategy can be readily extended to the selective recognition and sensitive detection of other molecules.

  10. PROTECTIVE EFFECT OF QUERCETIN, EGCG, CATECHIN AND BETAINE AGAINST OXIDATIVE STRESS INDUCED BY ETHANOL IN VITRO

    PubMed Central

    Oliva, Joan; Bardag-Gorce, Fawzia; Tillman, Brittany; French, Samuel W.

    2011-01-01

    There is a need for a nontoxic antioxidant agent to be identified which will prevent alcoholic liver disease (ALD) in alcoholic patients. We tested 4 candidate agents: quercetin, EGCG, catechin and betaine, all of which occur naturally in food. HepG2 cells over expressing CYP2E1 were subjected to arachidonic acid, iron and 100 mM ethanol with or without the antioxidant agent. All the agents prevented oxidative stress and MDA/4HNE formation induced by ethanol, except for EGCG. Catechin prevented CYP2E1 induction by ethanol. All the agents tended to down regulate the ethanol-induced increased expression of glutathionine peroxidase 4 (GPX4). All the agents, except catechin, tended to reduce the expression of SOD2 induced by ethanol. Heat shock protein 70 was up regulated by ethanol alone and betaine tended to prevent this. All 4 agents down regulated the expression of Gadd45b in the presence of ethanol, which could explain the mechanism of DNA demethylation associated with the up regulation of the gene expression observed in experimental ALD. In conclusion, the in vitro model of oxidative stress induced by ethanol provided evidence that all 4 agents tested prevented some aspect of liver cell injury caused by ethanol. PMID:21352821

  11. Protective Effect of Quercetin against Oxidative Stress and Brain Edema in an Experimental Rat Model of Subarachnoid Hemorrhage

    PubMed Central

    Dong, Yu-shu; Wang, Ju-lei; Feng, Da-yun; Qin, Huai-zhou; Wen, Hua; Yin, Zhong-min; Gao, Guo-dong; Li, Chuan

    2014-01-01

    Quercetin has been demonstrated to play an important role in altering the progression of ischemic brain injuries and neurodegenerative diseases by protecting against oxidative stress. The effects of quercetin on brain damage after subarachnoid hemorrhage (SAH), however, have not been investigated. This study was designed to explore the effects of quercetin on oxidative stress and brain edema after experimental SAH using four equal groups (n = 16) of adult male Sprague-Dawley (SD) rats, including a sham group, an SAH + vehicle group, an SAH + quercetin10 group, and an SAH + quercetin50 group. The rat SAH model was induced by injection of 0.3 ml of non-heparinised arterial blood into the prechiasmatic cistern. In the SAH + quercetin10 and SAH + quercetin50 groups, doses of 10 mg/kg and 50 mg/kg quercetin, respectively, were directly administered by intraperitoneal injection at 30 min, 12 h, and 24 h after SAH induction. Cerebral tissue samples were extracted for enzymatic antioxidant determination, lipid peroxidation assay, caspase-3 activity and water content testing 48 h after SAH. Treatment with a high dose (50 mg/kg) of quercetin markedly enhanced the activities of copper/zinc superoxide dismutase (CuZn-SOD) and glutathione peroxidase (GSH-Px), and treatment with this dose significantly reduced the level of malondialdehyde (MDA). Caspase-3 and brain edema was ameliorated and neurobehavioral deficits improved in rats that received the high dose of quercetin. The findings suggest that the early administration of optimal dose of quercetin may ameliorate brain damage and provide neuroprotection in the SAH model, potentially by enhancing the activity of endogenous antioxidant enzymes and inhibiting free radical generation. PMID:24516353

  12. Proliferative effect of histamine on MA-10 Leydig tumor cells mediated through HRH2 activation, transient elevation in cAMP production, and increased extracellular signal-regulated kinase phosphorylation levels.

    PubMed

    Pagotto, Romina María; Monzón, Casandra; Moreno, Marcos Besio; Pignataro, Omar Pedro; Mondillo, Carolina

    2012-06-01

    Mast cells (MC) occur normally in the testis with a species-specific distribution, yet their precise role remains unclear. Testicular MC express histidine decarboxylase (HDC), the unique enzyme responsible for histamine (HA) generation. Evidence to date supports a role for HA as a local regulator of steroidogenesis via functional H₁ and H₂ receptor subtypes (HRH1 and HRH2, respectively) present in Leydig cells. Given that HA is a well-known modulator of physiological and pathological proliferation in many different cell types, we aimed in the present study to evaluate whether HA might contribute to the regulation of Leydig cell number as well as to the control of androgen production. Herein, we demonstrate, to our knowledge for the first time, that MA-10 Leydig tumor cells, but not normal immature Leydig cells (ILC), exhibit a proliferative response upon stimulation with HA that involves HRH2 activation, transient elevation of cAMP levels, and increased extracellular signal-regulated kinase (ERK) phosphorylation. Our results also reveal that MA-10 cells show significantly heightened HDC expression compared to normal ILC or whole-testicular lysate and that inhibition of HDC activity decreases MA-10 cell proliferation, suggesting a possible correlation between autocrine overproduction of HA and abnormally increased proliferation in Leydig cells. The facts that germ cells are also both source and target of HA and that multiple testicular cells are susceptible to HA action underline the importance of the present study, which we hope will serve as a first step for further research into regulation of non-MC-related HDC expression within the testis and its significance for testicular function.

  13. Docking and DFT studies on ligand binding to Quercetin 2,3-dioxygenase.

    PubMed

    Malkhasian, Aramice Y S; Howlin, Brendan J

    2016-11-01

    Simple molecular docking calculations on quercetin, kojic acid and diethylcarbamatodithoic acid using the software package MOE are shown to be close to the geometries reported in the X-ray crystal structures of the protein co-crystallized with the respective ligands. Furthermore, DFT optimization of the docked conformations is shown to reproduce the essential features of previous studies on quercetin, showing that docking can be used to provide good starting structures for mechanistic study. The flavone ligand, lacking the hydroxyl group of the quercetin is shown by docking to be unable to approach closely the copper atom, indicating the necessity of the presence of the hydroxyl group and providing a prediction of the likely binding environment of this ligand.

  14. Complex formation of quercetin with lanthanum enhances binding to plant viral satellite double stranded RNA.

    PubMed

    Rusak, Gordana; Piantanida, Ivo; Bretschneider, Sabine; Ludwig-Müller, Jutta

    2009-12-01

    Due to the broad spectrum of biological activities of flavonoids, their target molecules in the cell are intensively studied. We examined the interactions of the flavonoid quercetin (Q) and its lanthanum complex (QLa(3+)) with very recently isolated plant viral satellite (sat) dsRNA. Comparison of the cumulative binding affinity and the estimated intercalative binding constant pointed towards an additional binding mode of quercetin to exclusively viral dsRNA, which is not recorded for synthetic dsRNAs. The QLa(3+) showed significantly higher affinity toward viral dsRNA than Q and La(3+) alone, most likely as the consequence of quercetin intercalation accompanied by additional electrostatic interaction of La(3+) with the negatively charged viral RNA backbone.

  15. Preliminary study of quercetin affecting the hypothalamic-pituitary-gonadal axis on rat endometriosis model.

    PubMed

    Cao, Yang; Zhuang, Meng-Fei; Yang, Ying; Xie, Shu-Wu; Cui, Jin-Gang; Cao, Lin; Zhang, Ting-Ting; Zhu, Yan

    2014-01-01

    In this study, the endometriosis rats model was randomly divided into 6 groups: model control group, ovariectomized group, Gestrinone group, and quercetin high/medium/low dose group. Rats were killed after 3 weeks of administration. The expression levels of serum FSH and LH were detected by ELISA. The localizations and quantities of ERα, ERβ, and PR were detected by immunohistochemistry and western blot. The results showed that the mechanism of quercetin inhibiting the growth of ectopic endometrium on rat endometriosis model may be through the decreasing of serum FSH and LH levels and then reducing local estrogen content to make the ectopic endometrium atrophy. Quercetin can decrease the expression of ERα, ERβ, and PR in hypothalamus, pituitary, and endometrium, thereby inhibiting estrogen and progesterone binding to their receptors to play the role of antiestrogen and progesterone.

  16. Preparation and optimization of quercetin-loaded liposomes for wound healing, using response surface methodology.

    PubMed

    Jangde, Rajendra; Singh, Deependra

    2016-01-01

    The basic objective of this study was to prepare quercetin-loaded liposomes by the thin film hydration method. The liposomal formulation was optimized using response surface methodology (RSM). A rotation speed of 75 rpm and a water bath temperature of 46°C were finalized as the best for optimized drug-loaded liposomal formulation. In vitro characterization of the quercetin-loaded liposomal formulation was done through some parameters including the entrapment efficiency (EE), drug release (DR), and mean particle size; the resulting values of 86.5 ± 0.42%, 76.5%, and146 nm were found to be standard characterized values respectively. It is concluded that quercetin-loaded liposomal formulations achieve sustained release of drug in wound areas. PMID:25375215

  17. Pharmacophore model of the quercetin binding site of the SIRT6 protein

    PubMed Central

    Ravichandran, S.; Singh, N.; Donnelly, D.; Migliore, M.; Johnson, P.; Fishwick, C.; Luke, Brian T.; Martin, B.; Maudsley, S.; Fugmann, S. D.; Moaddel, R.

    2014-01-01

    SIRT6 is a histone deacetylase that has been proposed as a potential therapeutic target for metabolic disorders and the prevention of age-associated diseases. We have previously reported on the identification of quercetin and vitexin as SIRT6 inhibitors, and studied structurally related flavonoids including luteolin, kaempferol, apigenin and naringenin. It was determined that the SIRT6 protein remained active after immobilization and that a single frontal displacement could correctly predict the functional activity of the immobilized enzyme. The previous study generated a preliminary pharmacophore for the quercetin binding site on SIRT6, containing 3 hydrogen bond donors and one hydrogen bond acceptor. In this study, we have generated a refined pharmacophore with an additional twelve quercetin analogs. The resulting model had a positive linear behavior between the experimental elution time verses the fit values obtained from the model with a correlation coefficient of 0.8456. PMID:24491483

  18. Relaxation behavior and nonlinear properties of thermally stable polymers based on glycidyl derivatives of quercetin

    NASA Astrophysics Data System (ADS)

    Mishurov, Dmytro; Voronkin, Andrii; Roshal, Alexander; Brovko, Oleksandr

    2016-07-01

    Cross-linked polymers on the basis of di-, tri and tetraglycidyl ethers of quercetin (3,3‧,4‧,5,7-pentahydroxyflavone) were synthesized, and then, poled in electrical field of corona discharge. Investigations of structural, thermal and optical parameters of the polymer films were carried out. It was found that the polymers obtained from di- and triglycidyl quercetin ethers had high values of macroscopic quadratic susceptibilities and substantial stability of nonlinear optical (NLO) properties after the poling. Tetraglycidyl ether of quercetin forms the polymer of lower quadratic susceptibility, which demonstrates noticeable relaxation process resulting in decrease of the NLO effect. It is supposed that the difference of the NLO properties is due to peculiarities of physical network of the polymers, namely to the ratio between numbers of hydrogen bonds formed by hydroxyl groups of chromophore fragments and by the ones of interfragmental parts of the polymeric chains.

  19. Efficient regioselective acylation of quercetin using Rhizopus oryzae lipase and its potential as antioxidant.

    PubMed

    Kumar, Vinod; Jahan, Firdaus; Mahajan, Richi V; Saxena, Rajendra Kumar

    2016-10-01

    The present investigation describes the regioselective enzymatic acylation of quercetin with ferulic acid using Rhizopus oryzae lipase. Optimization of reaction parameters resulted in 93.2% yield of the ester synthesized using 750IU of lipase in cyclo-octane at a temperature of 45°C. The reaction was successfully carried out upto 25g scale. The ester synthesized was analyzed by (1)H Nuclear magnetic resonance spectroscopy. The ester synthesized (quercetin ferulate) showed higher antiradical activity as compared to ascorbic acid using the 2,2-diphenyl-1-picrylhydrazyl radical method. These results on enzyme-catalyzed acylation of quercetin might be used to prepare and scale-up other flavonoids derivatives. PMID:27372535

  20. Efficient regioselective acylation of quercetin using Rhizopus oryzae lipase and its potential as antioxidant.

    PubMed

    Kumar, Vinod; Jahan, Firdaus; Mahajan, Richi V; Saxena, Rajendra Kumar

    2016-10-01

    The present investigation describes the regioselective enzymatic acylation of quercetin with ferulic acid using Rhizopus oryzae lipase. Optimization of reaction parameters resulted in 93.2% yield of the ester synthesized using 750IU of lipase in cyclo-octane at a temperature of 45°C. The reaction was successfully carried out upto 25g scale. The ester synthesized was analyzed by (1)H Nuclear magnetic resonance spectroscopy. The ester synthesized (quercetin ferulate) showed higher antiradical activity as compared to ascorbic acid using the 2,2-diphenyl-1-picrylhydrazyl radical method. These results on enzyme-catalyzed acylation of quercetin might be used to prepare and scale-up other flavonoids derivatives.

  1. Quercetin supplementation and upper respiratory tract infection: A randomized community clinical trial.

    PubMed

    Heinz, Serena A; Henson, Dru A; Austin, Melanie D; Jin, Fuxia; Nieman, David C

    2010-09-01

    Quercetin in culture with target cells and pathogens exerts anti-pathogenic activities against a wide variety of viruses and bacteria. A few small-scale human quercetin supplementation studies have produced conflicting results regarding quercetin's effects on upper respiratory tract infection rates, and little is known regarding the appropriate human dose. The purpose of this randomized, double-blinded, placebo-controlled trial was to measure the influence of two quercetin doses (500 and 1000 mg/day) compared to placebo on upper respiratory tract infection (URTI) rates in a large community group (N=1002) of subjects varying widely in age (18-85 years). Subjects ingested supplements for 12 weeks and logged URTI symptoms on a daily basis using the Wisconsin Upper Respiratory Symptom Survey (WURSS). No significant group differences were measured for URTI outcomes for all subjects combined, or when analyzing separately by gender, body mass index, and age categories. Regression analysis revealed that the strongest interaction effect with group status was self-reported fitness level. A separate analysis of subjects 40 years of age and older rating themselves in the top half of the entire group for fitness level (N=325) showed lower URTI severity (36% reduction, P=0.020) and URTI total sick days (31% reduction, P=0.048) for the Q-1000 group compared to placebo. In summary, for all subjects combined, quercetin supplementation over 12 weeks had no significant influence on URTI rates or symptomatology compared to placebo. A reduction in URTI total sick days and severity was noted in middle aged and older subjects ingesting 1000 mg quercetin/day for 12 weeks who rated themselves as physically fit.

  2. Quercetin abrogates IL-6/STAT3 signaling and inhibits glioblastoma cell line growth and migration

    SciTech Connect

    Michaud-Levesque, Jonathan; Bousquet-Gagnon, Nathalie; Beliveau, Richard

    2012-05-01

    Evidence has suggested that STAT3 functions as an oncogene in gliomagenesis. As a consequence, changes in the inflammatory microenvironment are thought to promote tumor development. Regardless of its origin, cancer-related inflammation has many tumor-promoting effects, such as the promotion of cell cycle progression, cell proliferation, cell migration and cell survival. Given that IL-6, a major cancer-related inflammatory cytokine, regulates STAT3 activation and is upregulated in glioblastoma, we sought to investigate the inhibitory effects of the chemopreventive flavonoid quercetin on glioblastoma cell proliferation and migration triggered by IL-6, and to determine the underlying mechanisms of action. In this study, we show that quercetin is a potent inhibitor of the IL-6-induced STAT3 signaling pathway in T98G and U87 glioblastoma cells. Exposure to quercetin resulted in the reduction of GP130, JAK1 and STAT3 activation by IL-6, as well as a marked decrease of the proliferative and migratory properties of glioblastoma cells induced by IL-6. Interestingly, quercetin also modulated the expression of two target genes regulated by STAT3, i.e. cyclin D1 and matrix metalloproteinase-2 (MMP-2). Moreover, quercetin reduced the recruitment of STAT3 at the cyclin D1 promoter and inhibited Rb phosphorylation in the presence of IL-6. Overall, these results provide new insight into the role of quercetin as a blocker of the STAT3 activation pathway stimulated by IL-6, with a potential role in the prevention and treatment of glioblastoma.

  3. Neuroprotective effects of quercetin, rutin and okra (Abelmoschus esculentus Linn.) in dexamethasone-treated mice.

    PubMed

    Tongjaroenbuangam, Walaiporn; Ruksee, Nootchanart; Chantiratikul, Piyanete; Pakdeenarong, Noppakun; Kongbuntad, Watee; Govitrapong, Piyarat

    2011-10-01

    The administration of dexamethasone, a synthetic glucocorticoid receptor agonist, causes neuronal death in the CA3 layer of the hippocampus, which has been associated with learning and memory impairments. This study aimed to examine the ability of okra (Abelmoschus esculentus Linn.) extract and its derivatives (quercetin and rutin) to protect neuronal function and improve learning and memory deficits in mice subjected to dexamethasone treatment. Learning and memory functions in mice were examined using the Morris water maze test. The results showed that the mice treated with dexamethasone had prolonged water maze performance latencies and shorter time spent in the target quadrant while mice pretreated with quercetin, rutin or okra extract prior to dexamethasone treatment showed shorter latencies and longer time spent in target quadrant. Morphological changes in pyramidal neurons were observed in the dexamethasone treated group. The number of CA3 hippocampal neurons was significantly lower while pretreated with quercetin, rutin or okra attenuated this change. Prolonged treatment with dexamethasone altered NMDA receptor expression in the hippocampus. Pretreatment with quercetin, rutin or okra extract prevented the reduction in NMDA receptor expression. Dentate gyrus (DG) cell proliferation was examined using the 5-bromo-2-deoxyuridine (BrdU) immunohistochemistry technique. The number of BrdU-immunopositive cells was significantly reduced in dexamethasone-treated mice compared to control mice. Pretreatment with okra extract, either quercetin or rutin was found to restore BrdU-immunoreactivity in the dentate gyrus. These findings suggest that quercetin, rutin and okra extract treatments reversed cognitive deficits, including impaired dentate gyrus (DG) cell proliferation, and protected against morphological changes in the CA3 region in dexamethasone-treated mice. The precise mechanism of the neuroprotective effect of these plant extracts should be further investigated.

  4. Quercetin supplementation is effective in improving mitochondrial dysfunctions induced by 3-nitropropionic acid: implications in Huntington's disease.

    PubMed

    Sandhir, Rajat; Mehrotra, Arpit

    2013-03-01

    The study was designed to investigate the beneficial effect of quercetin supplementation in 3-nitropropionic acid (3-NP) induced model of Huntington's disease (HD). HD was induced in rats by administering sub-chronic dose of 3-NP, intraperitoneally, twice daily for 17days. Quercetin was supplemented at a dose of 25mg/kg body weight by oral gavage for 21days. At the end of treatment, mitochondrial bioenergetics, mitochondrial swelling, oxidative stress, neurobehavioral deficits and histopathological changes were analyzed. Quercetin supplementation was able to reverse 3-NP induced inhibition of respiratory chain complexes, restore ATP levels, attenuate mitochondrial oxidative stress in terms of lipid peroxidation and prevent mitochondrial swelling. Quercetin administration also restored the activities of superoxide dismutase and catalase along with thiol content in 3-NP treated animals. Beneficial effect of quercetin administration was observed on 3-NP induced motor deficits analyzed by narrow beam walk and footprint analysis. Histopathological analysis of 3-NP treated rats revealed pyknotic nuclei and astrogliosis in striatum, which were reduced or absent in quercetin supplemented animals. Altogether, our results show that quercetin supplementation to 3-NP induced HD animals ameliorated mitochondrial dysfunctions, oxidative stress and neurobehavioral deficits in rats showing potential of this flavonoid in maintaining mitochondrial functions, suggesting a putative role of quercetin in HD management. PMID:23220257

  5. Response of keloid fibroblasts to Vitamin D3 and quercetin treatment - in vitro study.

    PubMed

    Mathangi Ramakrishnan, K; Babu, M; Lakshmi Madhavi, M S

    2015-09-30

    Keloid scars continue to pose a challenge to clinicians as the treatment armamentarium lacks a formidable agent to tackle them. We have undertaken an in vitro study based on the mechanism of action of Vitamin D3 and quercetin on isolated keloid fibroblasts. Dose-dependent action on the reduction of cellular proliferation, collagen synthesis and induction of apoptosis by Vitamin D3 and quercetin are analyzed and probable mechanism of action is elaborated. This study thus opens up newer avenues in tackling keloid scars effectively. PMID:27279805

  6. Quercetin supplementation attenuates the progression of cancer cachexia in ApcMin/+ mice.

    PubMed

    Velázquez, Kandy T; Enos, Reilly T; Narsale, Aditi A; Puppa, Melissa J; Davis, J Mark; Murphy, E Angela; Carson, James A

    2014-06-01

    Although there are currently no approved treatments for cancer cachexia, there is an intensified interest in developing therapies because of the high mortality index associated with muscle wasting diseases. Successful