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Sample records for quercetin transiently increases

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

    PubMed Central

    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. PMID:26558284

  2. Activation of transient receptor potential ankyrin 1 by quercetin and its analogs.

    PubMed

    Nakamura, Toshiyuki; Miyoshi, Noriyuki; Ishii, Takeshi; Nishikawa, Miyu; Ikushiro, Shinichi; Watanabe, Tatsuo

    2016-05-01

    The agonistic activity of quercetin and its analogs towards the transient receptor potential ankyrin 1 (TRPA1) has been experimentally investigated. The human TRPA1 was expressed in HEK293T cells using a tetracycline-inducible system. The activation of TRPA1 was evaluated by a fluo-4 fluorescence assay based on calcium sensing. The results of a structure-activity relationship study led to the selection of six flavonoids, all of which activated the TRPA1 channel in a dose-dependent manner. Notably, the activation of TRPA1 by these flavonoid aglycones was completely inhibited by the co-treatment of the HEK293T cells with the TRPA1-specific antagonist, HC-030031. Several flavonoid glycosides and metabolites were also evaluated, but did not activate the TRPA1 except for methylated quercetin. On the other hand, TRPV1 (vanilloid receptor) did not respond to any of the flavonoids evaluated in this study. Therefore, these data suggest that the flavonoids would be promising ligands for the TRPA1. PMID:26806540

  3. 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

  4. The flavonoid quercetin transiently inhibits the activity of taxol and nocodazole through interference with the cell cycle

    PubMed Central

    Samuel, Temesgen; Fadlalla, Khalda; Turner, Timothy; Yehualaeshet, Teshome E.

    2010-01-01

    Quercetin is a flavonoid with anticancer properties. In this study, we examined the effects of quercetin on cell cycle, viability and proliferation of cancer cells, either singly or in combination with the microtubule-targeting drugs taxol and nocodazole. Although quercetin induced cell death in a dose dependent manner, 12.5-50μM quercetin inhibited the activity of both taxol and nocodazole to induce G2/M arrest in various cell lines. Quercetin also partially restored drug-induced loss in viability of treated cells for up to 72 hours. This antagonism of microtubule-targeting drugs was accompanied by a delay in cell cycle progression and inhibition of the buildup of cyclin-B1 at the microtubule organizing center of treated cells. However, quercetin did not inhibit the microtubule targeting of taxol or nocodazole. Despite the short-term protection of cells by quercetin, colony formation and clonogenicity of HCT116 cells were still suppressed by quercetin or quercetin-taxol combination. The status of cell adherence to growth matrix was critical in determining the sensitivity of HCT116 cells to quercetin. We conclude that while long-term exposure of cancer cells to quercetin may prevent cell proliferation and survival, the interference of quercetin with cell cycle progression diminishes the efficacy of microtubule-targeting drugs to arrest cells at G2/M. PMID:21058190

  5. 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.

  6. 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

  7. 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...

  8. 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

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

    PubMed

    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

    2016-07-01

    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

  10. 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

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

    PubMed Central

    WANG, YIFEI; HAN, ALEX; CHEN, EVA; SINGH, RAKESH K.; CHICHESTER, CLINTON O.; MOORE, RICHARD G.; SINGH, AJAY P.; VORSA, NICHOLI

    2015-01-01

    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, phosphohistone 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

  12. 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

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

    PubMed Central

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

    2014-01-01

    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. PMID:26150744

  14. 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. PMID:26150744

  15. 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

  16. 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

  17. 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

  18. 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

  19. Quercetin in brain diseases: Potential and limits.

    PubMed

    Dajas, Federico; Abin-Carriquiry, Juan Andrés; Arredondo, Florencia; Blasina, Fernanda; Echeverry, Carolina; Martínez, Marcela; Rivera, Felicia; Vaamonde, Lucía

    2015-10-01

    Quercetin is a ubiquitous flavonoid present in beverages, food and plants that has been demonstrated to have a role in the prevention of neurodegenerative and cerebrovascular diseases. In neuronal culture, quercetin increases survival against oxidative insults. Antioxidation appears to be a necessary but not sufficient condition for its neuroprotective action and modulation of intracellular signaling and transcription factors, increasing the expression of antioxidant and pro survival proteins and modulating inflammation, appears as important for neuronal protection. Quercetin also regulates the activity of kinases, changing the phosphorylation state of target molecules, resulting in modulation of cellular function and gene expression. Concentrations of quercetin higher than 100 μM consistently show cytotoxic and apoptotic effects by its autoxidation and generation of toxic quinones. In vivo, results are controversial with some studies showing neuroprotection by quercetin and others not, requiring a drug delivery system or chronic treatments to show neuroprotective effects. The blood and brain bioavailability of free quercetin after ingestion is a complex and controversial process that produces final low concentrations, a fact that has led to suggestions that metabolites would be active by themselves and/or as pro-drugs that would release the active aglycone in the brain. Available studies show that in normal or low oxidative conditions, chronic treatments with quercetin contributes to re-establish the redox regulation of proteins, transcription factors and survival signaling cascades that promote survival. In the presence of highly oxidative conditions such as in an ischemic tissue, quercetin could become pro-oxidant and toxic. At present, evidence points to quercetin as a preventive molecule for neuropathology when administered in natural matrices such as vegetables and food. More research is needed to support its use as a lead compound in its free form in

  20. Reduction in the amplitude of shortening and Ca(2+) transient by phlorizin and quercetin-3-O-glucoside in ventricular myocytes from streptozotocin-induced diabetic rats.

    PubMed

    Hamouda, N N; Qureshi, M A; Alkaabi, J M; Oz, M; Howarth, F C

    2016-06-20

    Diabetes mellitus is the leading cause of cardiovascular morbidity and mortality. Phlorizin (PHLOR) and quercetin-3-O-glucoside (QUER-3-G) are two natural compounds reported to have antidiabetic properties by inhibiting sodium/glucose transporters. Their effects on ventricular myocyte shortening and intracellular Ca(2+) in streptozotocin (STZ)-induced diabetic rats were investigated. Video edge detection and fluorescence photometry were used to measure ventricular myocyte shortening and intracellular Ca(2+), respectively. Blood glucose in STZ rats was 4-fold higher (469.64+/-22.23 mg/dl, n=14) than in Controls (104.06+/-3.36 mg/dl, n=16). The amplitude of shortening was reduced by PHLOR in STZ (84.76+/-2.91 %, n=20) and Control (83.72+/-2.65 %, n=23) myocytes, and by QUER-3-G in STZ (79.12+/-2.28 %, n=20) and Control (76.69+/-1.92 %, n=30) myocytes. The amplitude of intracellular Ca(2+) was also reduced by PHLOR in STZ (82.37+/-3.16 %, n=16) and Control (73.94+/-5.22 %, n=21) myocytes, and by QUER-3-G in STZ (73.62+/-5.83 %, n=18) and Control (78.32+/-3.54 %, n=41) myocytes. Myofilament sensitivity to Ca(2+) was not significantly altered by PHLOR; however, it was reduced by QUER-3-G modestly in STZ myocytes and significantly in Controls. PHLOR and QUER-3-G did not significantly alter sarcoplasmic reticulum Ca(2+) in STZ or Control myocytes. Altered mechanisms of Ca(2+) transport partly underlie PHLOR and QUER-3-G negative inotropic effects in ventricular myocytes from STZ and Control rats. PMID:26447513

  1. Increased sensitivity to transient global ischemia in aging rat brain.

    PubMed

    Xu, Kui; Sun, Xiaoyan; Puchowicz, Michelle A; LaManna, Joseph C

    2007-01-01

    Transient global brain ischemia induced by cardiac arrest and resuscitation (CAR) results in reperfusion injury associated with oxidative stress. Oxidative stress is known to produce delayed selective neuronal cell loss and impairment of brainstem function, leading to post-resuscitation mortality. Levels of 4-hydroxy-2-nonenal (HNE) modified protein adducts, a marker of oxidative stress, was found to be elevated after CAR in rat brain. In this study we investigated the effects of an antioxidant, alpha-phenyl-tert-butyl-nitrone (PBN) on the recovery following CAR in the aged rat brain. Male Fischer 344 rats (6, 12 and 24-month old) underwent 7-minute cardiac arrest before resuscitation. Brainstem function was assessed by hypoxic ventilatory response (HVR) and HNE-adducts were measured by western blot analysis. Our data showed that in the 24-month old rats, overall survival rate, hippocampal CAl neuronal counts and HVR were significantly reduced compared to the younger rats. With PBN treatment, the recovery was improved in the aged rat brain, which was consistent with reduced HNE adducts in brain following CAR. Our data suggest that aged rats are more vulnerable to oxidative stress insult and treatment with PBN improves the outcome following reperfusion injury. The mechanism of action is most likely through the scavenging of reactive oxygen species resulting in reduced lipid peroxidation. PMID:17727265

  2. 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

  3. 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

  4. Transient increase of higher-order aberrations after lateral rectus recession in children.

    PubMed

    Seo, Kyoung Yul; Hong, Samin; Song, Won Kyoung; Chung, Seung Ah; Lee, Jong Bok

    2011-05-01

    The changes of higher-order aberrations (HOAs) after bilateral lateral rectus muscle recession were evaluated. Forty eyes of 20 children were enrolled and their wavefront information was assessed until postoperative 3 months. Even though the root mean square (RMS) of total aberration was not changed, the RMS of HOA was transiently increased at postoperative 1 week and returned to baseline level after 1 month. Among individual Zernike coefficient, secondary astigmatism, quadrafoil, secondary coma, secondary trefoil, and pentafoil showed similar tendency with the RMS of HOA. However, coma, trefoil, and spherical aberration were not changed. Regarding recession amount, it did not correlate with any Zernike coefficient. In summary, our data imply that the HOAs are transiently increased after lateral rectus recession surgery. These results are in collusion with previous reports that strabismus surgery induced transient corneal astigmatism. PMID:21488198

  5. Quercetin attenuates doxorubicin cardiotoxicity by modulating Bmi-1 expression

    PubMed Central

    Dong, Qinghua; Chen, Long; Lu, Qunwei; Sharma, Sherven; Li, Lei; Morimoto, Sachio; Wang, Guanyu

    2014-01-01

    Background and Purpose Doxorubicin-based chemotherapy induces cardiotoxicity, which limits its clinical application. We previously reported the protective effects of quercetin against doxorubicin-induced hepatotoxicity. In this study, we tested the effects of quercetin on the expression of Bmi-1, a protein regulating mitochondrial function and ROS generation, as a mechanism underlying quercetin-mediated protection against doxorubicin-induced cardiotoxicity. Experimental Approach Effects of quercetin on doxorubicin-induced cardiotoxicity was evaluated using H9c2 cardiomyocytes and C57BL/6 mice. Changes in apoptosis, mitochondrial function, oxidative stress and related signalling were evaluated in H9c2 cells. Cardiac function, serum enzyme activity and reactive oxygen species (ROS) generation were measured in mice after a single injection of doxorubicin with or without quercetin pre-treatment. Key Results In H9c2 cells, quercetin reduced doxorubicin-induced apoptosis, mitochondrial dysfunction, ROS generation and DNA double-strand breaks. The quercetin-mediated protection against doxorubicin toxicity was characterized by decreased expression of Bid, p53 and oxidase (p47 and Nox1) and by increased expression of Bcl-2 and Bmi-1. Bmi-1 siRNA abolished the protective effect of quercetin against doxorubicin-induced toxicity in H9c2 cells. Furthermore, quercetin protected mice from doxorubicin-induced cardiac dysfunction that was accompanied by reduced ROS levels and lipid peroxidation, but enhanced the expression of Bmi-1 and anti-oxidative superoxide dismutase. Conclusions and Implications Our results demonstrate that quercetin decreased doxorubicin-induced cardiotoxicity in vitro and in vivo by reducing oxidative stress by up-regulation of Bmi-1 expression. The findings presented in this study have potential applications in preventing doxorubicin-induced cardiomyopathy. PMID:24902966

  6. Dose-response to 3 months of quercetin-containing supplements on metabolite and quercetin conjugate profile in adults.

    PubMed

    Cialdella-Kam, Lynn; Nieman, David C; Sha, Wei; Meaney, Mary Pat; Knab, Amy M; Shanely, R Andrew

    2013-06-01

    Quercetin, a flavonol in fruits and vegetables, has been demonstrated to have antioxidant, anti-inflammatory and immunomodulating influences. The purpose of the present study was to determine if quercetin, vitamin C and niacin supplements (Q-500 = 500 mg/d of quercetin, 125 mg/d of vitamin C and 5 mg/d of niacin; Q-1000 = 1000 mg/d of quercetin, 250 mg/d of vitamin C and 10 mg/d of niacin) would alter small-molecule metabolite profiles and serum quercetin conjugate levels in adults. Healthy adults (fifty-eight women and forty-two men; aged 40-83 years) were assigned using a randomised double-blinded placebo-controlled trial to one of three supplement groups (Q-1000, Q-500 or placebo). Overnight fasted blood samples were collected at 0, 1 and 3 months. Quercetin conjugate concentrations were measured using ultra-performance liquid chromatography (UPLC)-MS/MS, and metabolite profiles were measured using two MS platforms (UPLC-quadrupole time-of-flight MS (TOFMS) and GC-TOFMS). Statistical procedures included partial least square discriminant analysis (PLS-DA) and linear mixed model analysis with repeated measures. After accounting for age, sex and BMI, quercetin supplementation was associated with significant shifts in 163 metabolites/quercetin conjugates (false discovery rate, P<0·05). The top five metabolite shifts were an increase in serum guaiacol, 2-oxo-4-methylthiobutanoic acid, allocystathionine and two bile acids. Inflammatory and oxidative stress metabolites were not affected. PLS-DA revealed a clear separation only between the 1000 mg/d and placebo groups (Q(2)Y = 0·763). The quercetin conjugate, isorhamnetin-3-glucuronide, had the highest concentration at 3 months followed by quercetin-3-glucuronide, quercetin-3-sulphate and quercetin diglucuronide. In human subjects, long-term quercetin supplementation exerts disparate and wide-ranging metabolic effects and changes in quercetin conjugate concentrations. Metabolic shifts were apparent at the 1000 mg

  7. 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.

  8. 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.

  9. Quercetin Affects Erythropoiesis and Heart Mitochondrial Function in Mice.

    PubMed

    Ruiz, Lina M; Salazar, Celia; Jensen, Erik; Ruiz, Paula A; Tiznado, William; Quintanilla, Rodrigo A; Barreto, Marlen; Elorza, Alvaro A

    2015-01-01

    Quercetin, a dietary flavonoid used as a food supplement, showed powerful antioxidant effects in different cellular models. However, recent in vitro and in vivo studies in mammals have suggested a prooxidant effect of quercetin and described an interaction with mitochondria causing an increase in O2 (∙-) production, a decrease in ATP levels, and impairment of respiratory chain in liver tissue. Therefore, because of its dual actions, we studied the effect of quercetin in vivo to analyze heart mitochondrial function and erythropoiesis. Mice were injected with 50 mg/kg of quercetin for 15 days. Treatment with quercetin decreased body weight, serum insulin, and ceruloplasmin levels as compared with untreated mice. Along with an impaired antioxidant capacity in plasma, quercetin-treated mice showed a significant delay on erythropoiesis progression. Heart mitochondrial function was also impaired displaying more protein oxidation and less activity for IV, respectively, than no-treated mice. In addition, a significant reduction in the protein expression levels of Mitofusin 2 and Voltage-Dependent Anion Carrier was observed. All these results suggest that quercetin affects erythropoiesis and mitochondrial function and then its potential use as a dietary supplement should be reexamined. PMID:26106459

  10. Chemotherapeutic potential of quercetin on human bladder cancer cells.

    PubMed

    Oršolić, Nada; Karač, Ivo; Sirovina, Damir; Kukolj, Marina; Kunštić, Martina; Gajski, Goran; Garaj-Vrhovac, Vera; Štajcar, Damir

    2016-07-28

    In an effort to improve local bladder cancer control, we investigated the cytotoxic and genotoxic effects of quercetin on human bladder cancer T24 cells. The cytotoxic effect of quercetin against T24 cells was examined by MTT test, clonogenic assay as well as DNA damaging effect by comet assay. In addition, the cytotoxic effect of quercetin on the primary culture of papillary urothelial carcinoma (PUC), histopathological stage T1 of low- or high-grade tumours, was investigated. Our analysis demonstrated a high correlation between reduced number of colony and cell viability and an increase in DNA damage of T24 cells incubated with quercetin at doses of 1 and 50 µM during short term incubation (2 h). At all exposure times (24, 48 and 72 h), the efficacy of quercetin, administered at a 10× higher dose compared to T24 cells, was statistically significant (P < 0.05) for the primary culture of PUC. In conclusion, our study suggests that quercetin could inhibit cell proliferation and colony formation of human bladder cancer cells by inducing DNA damage and that quercetin may be an effective chemopreventive and chemotherapeutic agent for papillary urothelial bladder cancer after transurethral resection. PMID:27149655

  11. 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

  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. 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.

  14. Effect of quercetin on apoptosis of PANC-1 cells

    PubMed Central

    Lee, Joo Hyun; Lee, Han-Beom; Jung, Gum O; Oh, Jung Taek; Park, Dong Eun

    2013-01-01

    Purpose To investigate the chemotherapeutic effect of quercetin against cancer cells, signaling pathway of apoptosis was explored in human pancreatic cells. Methods Various anticancer drugs including adriamycin, cisplatin, 5-fluorouracil (5-FU) and gemcitabine were used. Cell viability was measured by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphe-nyltetra zolium bromide assay. Apoptosis was determined by 4'-6-diamidino-2-phenylindole nuclei staining and flow cytometry in PANC-1 cells treated with 50 µg/mL quercetin for 24 hours. Expression of endoplas mic reticulum (ER) stress mediators including, Grp78/Bip, p-PERK, PERK, ATF4, ATF6 and GADD153/CHOP proteins were measured by Western blot analysis. Mitochondrial membrane potential was measured by fluorescence staining with JC-1, rhodamine 123. Quercetin induced the apoptosis of PANC-1, which was characterized as nucleic acid and genomic DNA fragmentation, chromatin condensation, and sub-G0/G1 fraction of cell cycle increase. But not adriamycin, cisplatin, gemcitabine, and 5-FU. PANC-1 cells were markedly sensitive to quercetin. Results Treatment with quercetin resulted in the increased accumulation of intracellular Ca2+ ion. Treatment with quercetin also increased the expression of Grp78/Bip and GADD153/CHOP protein and induced mitochondrial dysfunction. Quercetin exerted cytotoxicity against human pancreatic cancer cells via ER stress-mediated apoptotic signaling including reactive oxygen species production and mitochondrial dysfunction. Conclusion These data suggest that quercetin may be an important modulator of chemosensitivity of cancer cells against anticancer chemotherapeutic agents. PMID:24368982

  15. 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

  16. Transient energy deficit induced by exercise increases 24-h fat oxidation in young trained men.

    PubMed

    Iwayama, Kaito; Kawabuchi, Ryosuke; Park, Insung; Kurihara, Reiko; Kobayashi, Masashi; Hibi, Masanobu; Oishi, Sachiko; Yasunaga, Koichi; Ogata, Hitomi; Nabekura, Yoshiharu; Tokuyama, Kumpei

    2015-01-01

    Whole body fat oxidation increases during exercise. However, 24-h fat oxidation on a day with exercise often remains similar to that of sedentary day, when energy intake is increased to achieve an energy-balanced condition. The present study aimed to examine a possibility that time of the day when exercise is performed makes differences in 24-h fat oxidation. As a potential mechanism of exercise affecting 24-h fat oxidation, its relation to exercise-induced transient energy deficit was examined. Nine young male endurance athletes underwent three trials of indirect calorimetry using a metabolic chamber, in which they performed a session of 100 min of exercise before breakfast (AM), after lunch (PM), or two sessions of 50 min of exercise before breakfast and after lunch (AM/PM) at 65% of maximal oxygen uptake. Experimental meals were designed to achieve individual energy balance. Twenty-four-hour energy expenditure was similar among the trials, but 24-h fat oxidation was 1,142 ± 97, 809 ± 88, and 608 ± 46 kcal/24 h in descending order of its magnitude for AM, AM/PM, and PM, respectively (P < 0.05). Twenty-four-hour carbohydrate oxidation was 2,558 ± 110, 2,374 ± 114, and 2,062 ± 96 kcal/24 h for PM, AM/PM, and AM, respectively. In spite of energy-balanced condition over 24 h, exercise induced a transient energy deficit, the magnitude of which was negatively correlated with 24-h fat oxidation (r = -0.72, P < 0.01). Similarly, transient carbohydrate deficit after exercise was negatively correlated with 24-h fat oxidation (r = -0.40, P < 0.05). The time of the day when exercise is performed affects 24-h fat oxidation, and the transient energy/carbohydrate deficit after exercise is implied as a factor affecting 24-h fat oxidation. PMID:25554797

  17. Effect of quercetin and its metabolites isorhamnetin and quercetin-3-glucuronide on inflammatory gene expression: role of miR-155.

    PubMed

    Boesch-Saadatmandi, Christine; Loboda, Agnieszka; Wagner, Anika E; Stachurska, Anna; Jozkowicz, Alicja; Dulak, Jozef; Döring, Frank; Wolffram, Siegfried; Rimbach, Gerald

    2011-03-01

    In the present study the effect of quercetin and its major metabolites quercetin-3-glucuronide (Q3G) and isorhamnetin on inflammatory gene expression was determined in murine RAW264.7 macrophages stimulated with lipopolysaccharide. Quercetin and isorhamnetin but not Q3G significantly decreased mRNA and protein levels of tumor necrosis factor alpha. Furthermore a significant decrease in mRNA levels of interleukin 1β, interleukin 6, macrophage inflammatory protein 1α and inducible nitric oxide synthase was evident in response to the quercetin treatment. However Q3G did not affect inflammatory gene expression. Anti-inflammatory properties of quercetin and isorhamnetin were accompanied by an increase in heme oxygenase 1 protein levels, a downstream target of the transcription factor Nrf2, known to antagonize chronic inflammation. Furthermore, proinflammatory microRNA-155 was down-regulated by quercetin and isorhamnetin but not by Q3G. Finally, anti-inflammatory properties of quercetin were confirmed in vivo in mice fed quercetin-enriched diets (0.1 mg quercetin/g diet) over 6 weeks. PMID:20579867

  18. 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

  19. Binding, stability, and antioxidant activity of quercetin with soy protein isolate particles.

    PubMed

    Wang, Yufang; Wang, Xiaoyong

    2015-12-01

    This work is to study the potential of particles fabricated from soy protein isolate (SPI) as a protective carrier for quercetin. When the concentration of SPI particles increases from 0 to 0.35 g/L, quercetin gives a gradually increased fluorescence intensity and fluorescence anisotropy. The addition of quercetin can highly quench the intrinsic fluorescence of SPI particles. These results are explained in terms of the binding of quercetin to the hydrophobic pockets of SPI particles mainly through the hydrophobic force together with the hydrogen bonding. The small difference in the binding constants at 25 and 40 °C suggests the structural stability of SPI particles. The relative changes in values of Gibbs energy, enthalpy, and entropy indicate that the binding of quercetin with SPI particles is spontaneous and hydrophobic interaction is the major force. Furthermore, SPI particles are superior to native SPI for improving the stability and radical scavenging activity of quercetin. PMID:26041159

  20. 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

  1. Serotonin increases intracellular Ca2+ transients in voltage-clamped sensory neurons of Aplysia californica.

    PubMed Central

    Boyle, M B; Klein, M; Smith, S J; Kandel, E R

    1984-01-01

    Noxious stimulation of the tail of Aplysia californica produces behavioral sensitization; it enhances several related defensive reflexes. This reflex enhancement involves heterosynaptic facilitation of transmitter release from sensory neurons of the reflex. The facilitation is stimulated by serotonin (5-HT) and involves suppression of a 5-HT-sensitive K+ current (the S current). Suppression of the S current broadens the action potential of the sensory neurons and is thought to enhance transmitter release by prolonging entry of Ca2+ in the presynaptic terminals. We now report a component of enhanced Ca2+ accumulation that is independent of changes in spike shape. We have measured intracellular free Ca2+ transients during long depolarizing steps in voltage-clamped sensory neuron cell bodies injected with the Ca2+-sensitive dye arsenazo III. The free Ca2+ transients elicited by a range of depolarizing voltage-clamp steps increase in amplitude by 75% following application of 5-HT. Since it is observed under voltage-clamp conditions, this increase in the free Ca2+ transients is not merely secondary to the changes in K+ current but must reflect an additional mechanism, an intrinsic change in the handling of Ca2+ by the cell. We have not yet determined whether this change in Ca2+ handling reflects an increase in Ca2+ influx, a reduction in intracellular Ca2+ uptake, or a release of Ca2+ from intracellular stores. Regardless of the underlying mechanism, however, it seems possible that the enhancement of Ca2+ accumulation and the reduction in K+ current act synergistically in producing short-term presynaptic facilitation. Alternatively, this additional modulation of Ca2+ by 5-HT might contribute to processes such as classical conditioning or long-term sensitization that may depend on Ca2+. PMID:6594707

  2. Quercetin phospholipid complex significantly protects against oxidative injury in ARPE-19 cells associated with activation of Nrf2 pathway.

    PubMed

    Xu, Xin-Rong; Yu, Hai-Tao; Yang, Yan; Hang, Li; Yang, Xue-Wen; Ding, Shu-Hua

    2016-01-01

    Age-related macular degeneration (AMD) is a major cause of blindness worldwide. Oxidative stress plays a crucial role in the pathogenesis of dry AMD. Quercetin has potent anti-oxidative activities, but poor bioavailability limits its therapeutic application. Herein, we prepared the phospholipid complex of quercetin (quercetin-PC), characterized its structure by differential scanning calorimetry, infrared spectrum and x-ray diffraction. Quercetin-PC had equilibrium solubility of 38.36 and 1351.27μg/ml in water and chloroform, respectively, which was remarkably higher than those of quercetin alone. Then we established hydrogen peroxide (H2O2)-induced oxidative injury model in human ARPE-19 cells to examine the effects of quercetin-PC. Quercetin-PC, stronger than quercetin, promoted cell proliferation, and the proliferation rate was increased to be 78.89% when treated with Quercetin-PC at 400μM. Moreover, quercetin-PC effectively prevented ARPE-19 cells from apoptosis, and the apoptotic rate was reduced to be 3.1% when treated with Quercetin-PC at 200μM. In addition, quercetin-PC at 200μM significantly increased the activities of SOD, CAT and GSH-PX, and reduced the levels of reactive oxygen species and MDA in H2O2-treated ARPE-19 cells, but quercetin at 200μM failed to do so. Molecular examinations revealed that quercetin-PC at 200μM significantly activated Nrf2 nuclear translocation and significantly enhanced the expression of target genes HO-1, NQO-1 and GCL by different folds at both mRNA and protein levels. Our current data collectively indicated that quercetin-PC had stronger protective effects against oxidative-induced damages in ARPE-19 cells, which was associated with activation of Nrf2 pathway and its target genes implicated in antioxidant defense. PMID:26643168

  3. 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

  4. Irisin in Blood Increases Transiently after Single Sessions of Intense Endurance Exercise and Heavy Strength Training

    PubMed Central

    Nygaard, Håvard; Slettaløkken, Gunnar; Vegge, Geir; Hollan, Ivana; Whist, Jon Elling; Strand, Tor; Rønnestad, Bent R.; Ellefsen, Stian

    2015-01-01

    Purpose Irisin is a recently identified exercise-induced hormone that increases energy expenditure, at least in rodents. The main purpose of this study was to test the hypothesis that Irisin increases acutely in blood after singular sessions of intense endurance exercise (END) and heavy strength training (STR). Secondary, we wanted to explore the relationship between body composition and exercise-induced effects on irisin, and the effect of END and STR on muscular expression of the irisin gene FNDC5. Methods Nine moderately trained healthy subjects performed three test days using a randomized and standardized crossover design: one day with 60 minutes of END, one day with 60 minutes of STR, and one day without exercise (CON). Venous blood was sampled over a period of 24h on the exercise days. Results Both END and STR led to transient increases in irisin concentrations in blood, peaking immediately after END and one hour after STR, before gradually returning to baseline. Irisin responses to STR, but not END, showed a consistently strong negative correlation with proportions of lean body mass. Neither END nor STR affected expression of FNDC5, measured 4h after training sessions, though both protocols led to pronounced increases in PGC-1α expression, which is involved in transcriptional control of FNDC5. Conclusion The results strongly suggest that single sessions of intense endurance exercise and heavy strength training lead to transient increases in irisin concentrations in blood. This was not accompanied by increased FNDC5 expression, measured 4h post-exercise. The results suggest that irisin responses to resistance exercise are higher in individuals with lower proportions of lean body mass. PMID:25781950

  5. Transient proteolytic modification of mesenchymal stromal cells increases lung clearance rate and targeting to injured tissue.

    PubMed

    Kerkelä, Erja; Hakkarainen, Tanja; Mäkelä, Tuomas; Raki, Mari; Kambur, Oleg; Kilpinen, Lotta; Nikkilä, Janne; Lehtonen, Siri; Ritamo, Ilja; Pernu, Roni; Pietilä, Mika; Takalo, Reijo; Juvonen, Tatu; Bergström, Kim; Kalso, Eija; Valmu, Leena; Laitinen, Saara; Lehenkari, Petri; Nystedt, Johanna

    2013-07-01

    Systemic infusion of therapeutic cells would be the most practical and least invasive method of administration in many cellular therapies. One of the main obstacles especially in intravenous delivery of cells is a massive cell retention in the lungs, which impairs homing to the target tissue and may decrease the therapeutic outcome. In this study we showed that an alternative cell detachment of mesenchymal stromal/stem cells (MSCs) with pronase instead of trypsin significantly accelerated the lung clearance of the cells and, importantly, increased their targeting to an area of injury. Cell detachment with pronase transiently altered the MSC surface protein profile without compromising cell viability, multipotent cell characteristics, or immunomodulative and angiogenic potential. The transient modification of the cell surface protein profile was sufficient to produce effective changes in cell rolling behavior in vitro and, importantly, in the in vivo biodistribution of the cells in mouse, rat, and porcine models. In conclusion, pronase detachment could be used as a method to improve the MSC lung clearance and targeting in vivo. This may have a major impact on the bioavailability of MSCs in future therapeutic regimes. PMID:23734061

  6. Transient Proteolytic Modification of Mesenchymal Stromal Cells Increases Lung Clearance Rate and Targeting to Injured Tissue

    PubMed Central

    Hakkarainen, Tanja; Mäkelä, Tuomas; Raki, Mari; Kambur, Oleg; Kilpinen, Lotta; Nikkilä, Janne; Lehtonen, Siri; Ritamo, Ilja; Pernu, Roni; Pietilä, Mika; Takalo, Reijo; Juvonen, Tatu; Bergström, Kim; Kalso, Eija; Valmu, Leena; Laitinen, Saara; Lehenkari, Petri; Nystedt, Johanna

    2013-01-01

    Systemic infusion of therapeutic cells would be the most practical and least invasive method of administration in many cellular therapies. One of the main obstacles especially in intravenous delivery of cells is a massive cell retention in the lungs, which impairs homing to the target tissue and may decrease the therapeutic outcome. In this study we showed that an alternative cell detachment of mesenchymal stromal/stem cells (MSCs) with pronase instead of trypsin significantly accelerated the lung clearance of the cells and, importantly, increased their targeting to an area of injury. Cell detachment with pronase transiently altered the MSC surface protein profile without compromising cell viability, multipotent cell characteristics, or immunomodulative and angiogenic potential. The transient modification of the cell surface protein profile was sufficient to produce effective changes in cell rolling behavior in vitro and, importantly, in the in vivo biodistribution of the cells in mouse, rat, and porcine models. In conclusion, pronase detachment could be used as a method to improve the MSC lung clearance and targeting in vivo. This may have a major impact on the bioavailability of MSCs in future therapeutic regimes. PMID:23734061

  7. 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

  8. Transient focal cortical increase of interictal glucose metabolism in Sturge-Weber syndrome: Implications for epileptogenesis

    PubMed Central

    Alkonyi, Bálint; Chugani, Harry T.; Juhász, Csaba

    2011-01-01

    SUMMARY Purpose To investigate clinical correlates and longitudinal course of interictal focal cortical glucose hypermetabolism in children with Sturge-Weber syndrome (SWS). Methods FDG PET scans of 60 children (age range: 3 months-15.2 years) with Sturge-Weber syndrome and epilepsy were assessed prospectively and serially for focal hypo- or hypermetabolism. Thirty-two patients had two or more consecutive PET scans. Age, seizure variables and the occurrence of epilepsy surgery were compared between patients with and without focal hypermetabolism. The severity of focal hypermetabolism was also assessed and correlated with seizure variables. Key Findings Interictal cortical glucose hypermetabolism, ipsilateral to the angioma, was seen in 9 patients, with the most common location in the frontal lobe. Age was lower in patients with hypermetabolism than in those without (p=0.022). In addition, time difference between the onset of first seizure and the first PET scan was much shorter in children with increased glucose metabolism than in those without (mean: 1.0 vs. 3.6 years; p=0.019). Increased metabolism was transient and switched to hypometabolism in all five children where follow-up scans were available. Focal glucose hypermetabolism occurred in 28 % of children under the age of two years. Children with transient hypermetabolism had a higher rate of subsequent epilepsy surgery as compared to those without hypermetabolism (p=0.039). Significance Interictal glucose hypermetabolism in young children with SWS is most often seen within a short time before or after the onset of first clinical seizures, i.e., the presumed period of epileptogenesis. Increased glucose metabolism detected by PET predicts future demise of the affected cortex based on a progressive loss of metabolism and may be an imaging marker of the most malignant cases of intractable epilepsy requiring surgery in SWS. PMID:21480889

  9. Transient increase of serum IgD levels after allogeneic bone-marrow transplantation.

    PubMed Central

    Korver, K; Radl, J; Schellekens, P T; Vossen, J M

    1988-01-01

    Serum IgD levels were followed longitudinally twice a week for up to 100 days in 60 children undergoing allogeneic bone-marrow transplantation (n = 52) or immunosuppression (n = 8) for the treatment of leukaemia, severe aplastic anaemia or severe combined immunodeficiency. In 40 out of the 49 post-transplantation periods analysed (82%), a transient sharp increase of serum IgD was detected, irrespective of initial disease. A similar peak was found in one out of five children after immunosuppressive treatment. A second IgD peak was only recorded in grafted patients (14/49 post-transfusion periods). Peak levels of IgD ranged from 1.3 to 185.7 IU/ml (median 12.2 IU/ml), which represents a 2.6 to 22.4-fold increase over 'baseline' levels. In the transplanted leukaemia and aplastic anaemia patients, the rise of serum IgD occurred at the same time (geometric mean 16 days after transplantation) and was shown to represent heterogeneous polyclonal IgD in six of them. The onset of the serum IgD peak was significantly delayed in children suffering from severe combined immunodeficiency (P less than 0.05) and was demonstrated in one patient to consist of homogeneous IgD. No relation was found between either the occurrence of clinical acute graft-versus-host disease or infections after treatment, and the time of onset of IgD elevations. To detect transient serum IgD peaks as described here, frequent sampling of sera is necessary. The origin of the early IgD peaks seems to reside within the recipient's cells by an unknown mechanism. The late IgD peaks are most probably an expression of gradual reconstitution of the immune system following bone-marrow transplantation. PMID:3044651

  10. 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

  11. Protective Effect of Quercetin on Posttraumatic Cardiac Injury.

    PubMed

    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 [Ca(2+)]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 [Ca(2+)]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 Ca(2+) overload in cardiomyocytes, representing a potential preventive approach for the treatment of secondary cardiac injury after mechanical trauma. PMID:27470932

  12. Transient increase of ATP as a response to temperature up-shift in Escherichia coli

    PubMed Central

    Soini, Jaakko; Falschlehner, Christina; Mayer, Christina; Böhm, Daniela; Weinel, Stefan; Panula, Johanna; Vasala, Antti; Neubauer, Peter

    2005-01-01

    Background Escherichia coli induces the heat shock response to a temperature up-shift which is connected to the synthesis of a characteristic set of proteins, including ATP dependent chaperones and proteases. Therefore the balance of the nucleotide pool is important for the adaptation and continuous function of the cell. Whereas it has been observed in eukaryotic cells, that the ATP level immediately decreased after the temperature shift, no data are available for E. coli about the adenosine nucleotide levels during the narrow time range of minutes after a temperature up-shift. Results The current study shows that a temperature up-shift is followed by a very fast significant transient increase of the cellular ATP concentration within the first minutes. This increase is connected to a longer lasting elevation of the cellular respiration and glucose uptake. Also the mRNA level of typical heat shock genes increases within only one minute after the heat-shock. Conclusion The presented data prove the very fast response of E. coli to a heat-shock and that the initial response includes the increase of the ATP pool which is important to fulfil the need of the cell for new syntheses, as well as for the function of chaperones and proteases. PMID:15804347

  13. Increased rhythmicity in hypertensive arterial smooth muscle is linked to transient receptor potential canonical channels.

    PubMed

    Chen, Xiaoping; Yang, Dachun; Ma, Shuangtao; He, Hongbo; Luo, Zhidan; Feng, Xiaoli; Cao, Tingbing; Ma, Liqun; Yan, Zhencheng; Liu, Daoyan; Tepel, Martin; Zhu, Zhiming

    2010-10-01

    Vasomotion describes oscillations of arterial vascular tone due to synchronized changes of intracellular calcium concentrations. Since increased calcium influx into vascular smooth muscle cells from spontaneously hypertensive rats (SHR) has been associated with variances of transient receptor potential canonical (TRPC) channels, in the present study we tested the hypothesis that increased vasomotion in hypertension is directly linked to increased TRPC expression. Using a small vessel myograph we observed significantly increased norepinephrine-induced vasomotion in mesenteric arterioles from SHR compared to normotensive Wistar-Kyoto (WKY) rats. Using immunoblottings we obtained significantly increased expression of TRPC1, TRPC3 and TRPC5 in mesenteric arterioles from SHR compared to WKY, whereas TRPC4 and TRPC6 showed no differences. Norepinephrine-induced vasomotion from SHR was significantly reduced in the presence of verapamil, SKF96365, 2-aminoethoxydiphenylborane (2-APB) or gadolinium. Pre-incubation of mesenteric arterioles with anti-TRPC1 and anti-TRPC3 antibodies significantly reduced norepinephrine-induced vasomotion and calcium influx. Control experiments with pre-incubation of TRPC antibodies plus their respective antigenic peptide or in the presence of anti-β-actin antibodies or random immunoglobulins not related to TRPC channels showed no inhibitory effects of norepinephrine-induced vasomotion and calcium influx. Administration of candesartan or telmisartan, but not amlodipine to SHR for 16 weeks significantly reduced either the expression of TRPC1, TRPC3 and TRPC5 as well as norepinephrine-induced vasomotion in mesenteric arterioles. In conclusion we gave experimental evidence that the increased TRPC1, TRPC3 and TRPC5 expression in mesenteric arterioles from SHR causes increased vasomotion in hypertension. PMID:19725917

  14. Oral administration of quercetin inhibits bone loss in rat model of diabetic osteopenia.

    PubMed

    Liang, Wei; Luo, Zhonghua; Ge, Shuhua; Li, Mo; Du, Junjie; Yang, Min; Yan, Ming; Ye, Zhengxu; Luo, Zhuojing

    2011-11-16

    Diabetic osteopenia can result in an increased incidence of bone fracture and a delay in fracture healing. Quercetin, one of the most widely distributed flavonoids in plants, possesses antioxidant property and beneficial effect on osteoporosis in ovariectomized mice. All these properties make quercetin a potential candidate for controlling the development of diabetic osteopenia. Therefore, the present study was designed to investigate the putative beneficial effect of quercetin on diabetic osteopenia in rats. Diabetes mellitus was induced by streptozotocin. The diabetic rats received daily oral administration of quercetin (5mg/kg, 30 mg/kg and 50mg/kg) for 8 weeks, which was started at 4 weeks after streptozotocin injection. Quercetin at 5mg/kg showed little effect on diabetic osteopenia, while quercetin at 30 mg/kg and 50mg/kg could increase the decreased serum osteocalcin, serum alkaline phosphatase activity, and urinary deoxypyridinoline in diabetic rats. In addition, quercetin (30 mg/kg and 50mg/kg) could partially reverse the decreased biomechanical quality and the impaired micro-architecture of the femurs in diabetic rats. Histomorphometric analysis showed that both decreased bone formation and resorption were observed in diabetic rats, which was partially restored by quercetin (30 mg/kg and 50mg/kg). Further investigations showed that quercetin significantly lowered the oxidative DNA damage level, up-regulated the total serum antioxidant capability and the activity of serum antioxidants in diabetic rats. All those findings indicate the beneficial effect of quercetin on diabetic osteopenia in rats, and raise the possibility of developing quercetin as potential drugs or an ingredient in diet for controlling diabetic osteopenia. PMID:21914440

  15. Effects of transient temperature increases on odor production from thermophilic anaerobic digestion.

    PubMed

    Iranpour, R; Alatriste-Mondragon, F; Cox, H H J; Haug, R T

    2005-01-01

    The City of Los Angeles, Bureau of Sanitation, has implemented thermophilic anaerobic sludge digestion at the Hyperion and Terminal Island Treatment Plants (HTP and TITP). A two-stage continuous-batch process was established at HTP, while a single-stage sequencing batch process was established at TITP. This was to evaluate compliance with the Class A pathogen reduction requirements of U.S. EPA 40 CFR Part 503. A rapid increase of the digester temperature at TITP from 57.5 to 65.5 degrees C caused an increase of the volatile fatty acid to alkalinity ratio, a decline in digester performance, and an elevated production of methyl mercaptan and hydrogen sulfide. A rapid increase of the digester temperature at HTP from 54 to 58 degrees C caused an elevated production of methyl mercaptan, but the effect on the volatile fatty acid to alkalinity ratio and digester performance was insignificant. It is likely that these effects observed at TITP and HTP were transient responses to rapid changes in temperature. PMID:16180433

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

    PubMed

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

    2015-11-13

    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 CO(2) increasing at 1% yr(-1)) during the second doubling of CO(2) 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, CO(2) radiative forcing may rise more rapidly than logarithmically with CO(2) concentration. Third, the climate feedback parameter may decline as the CO(2) 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 CO(2) in 1pctCO2 than with the TCR, and we suggest that the TCR may be underestimated from observed climate change. PMID:26438279

  17. 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

  18. 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

  19. Transient increase in HDL-cholesterol during weight gain by hyperalimentation in healthy subjects.

    PubMed

    Lindström, Torbjörn; Kechagias, Stergios; Carlsson, Martin; Nystrom, Fredrik H

    2011-04-01

    Determination of lipid levels is fundamental in cardiovascular risk assessment. We studied the short-term effects of fast food-based hyperalimentation on lipid levels in healthy subjects. Twelve healthy men and six healthy women with a mean age of 26 ± 6.6 years and an aged-matched control group were recruited for this prospective interventional study. Subjects in the intervention group aimed for a body weight increase of 5-15% by doubling the baseline caloric intake by eating at least two fast food-based meals a day in combination with adoption of a sedentary lifestyle for 4 weeks. This protocol induced a weight gain from 67.6 ± 9.1 kg to 74.0 ± 11 kg (P < 0.001). A numerical increase in the levels of high-density lipoprotein (HDL)-cholesterol occurred in all subjects during the study and this was apparent already at the first week in 16/18 subjects (mean increase at week 1: +22.0 ± 16%, range from -7 to +50%), whereas the highest level of HDL during the study as compared with baseline values varied from +6% to +58% (mean +31.6 ± 15%). The intake of saturated fat in the early phase of the trial related positively with the HDL-cholesterol-increase in the second week (r = 0.53, P = 0.028). Although the levels of insulin doubled at week 2, the increase in low-density lipoprotein (LDL)-cholesterol was only +12 ± 17%, and there was no statistically significant changes in fasting serum triglycerides. We conclude that hyperalimentation can induce a fast but transient increase in HDL-cholesterol that is of clinical interest when estimating cardiovascular risk based on serum lipid levels. PMID:20814413

  20. Effects of quercetin on oxidative stress and memory retrieval in kindled rats.

    PubMed

    Nassiri-Asl, Marjan; Moghbelinejad, Sahar; Abbasi, Esmail; Yonesi, Fatemeh; Haghighi, Mohammad-Reza; Lotfizadeh, Mina; Bazahang, Parisa

    2013-08-01

    Flavonoids are a class of polyphenolic compounds present in fruits and vegetables. Several studies have demonstrated a relationship between the consumption of flavonoid-rich diets and the prevention of human diseases including neurodegenerative disorders. Thus, we assessed the effect of quercetin (3,3',4',5,7-pentahydroxyflavone) on oxidative stress and memory retrieval using a step-through passive avoidance task in kindled rats. Quercetin (25, 50, and 100 mg/kg) was administered intraperitoneally (i.p.) before pentylenetetrazole (PTZ) every other day prior to the training. Retention tests were performed to assess memory in rats. Compared to control, pretreatment with 50 mg/kg of quercetin could attenuate seizure severity from the beginning of the kindling experiment by lowering the mean seizure stages. Moreover, quercetin 50 mg/kg significantly increased the step-through latency of the passive avoidance response compared to the control in the retention test. Malondialdehyde (MDA) levels were significantly increased in the quercetin groups compared to the PTZ group in the hippocampus and cerebral cortex following PTZ kindling. In the quercetin groups, higher sulfhydryl (SH) contents were not observed compared to the PTZ group. These results indicate that quercetin at a specific dose results in decreased seizure severity during kindling and performance improvement in a passive avoidance task in kindled rats. All doses of quercetin led to increased oxidative stress in the hippocampi and cerebral cortices of kindled rats. PMID:23747498

  1. 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

  2. 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

  3. Quercetin prevents experimental glucocorticoid-induced osteoporosis: a comparative study with alendronate.

    PubMed

    Derakhshanian, Hoda; Djalali, Mahmoud; Djazayery, Abolghassem; Nourijelyani, Keramat; Ghadbeigi, Sajad; Pishva, Hamideh; Saedisomeolia, Ahmad; Bahremand, Arash; Dehpour, Ahmad Reza

    2013-05-01

    Glucocorticoid-induced osteoporosis (GIO) is the most common type of secondary osteoporosis. The aim of this study was to compare the efficacy of quercetin, a plant-derived flavonoid, with alendronate in the prevention of GIO. Fifty-six Sprague-Dawley rats were randomly distributed among 7 groups (8 rats per group) and treated for 6 weeks with one of the following: (i) normal saline; (ii) 40 mg methylprednisolone sodium succinate (MP)/kg body mass; (iii) MP + 40 μg alendronate/kg; (iv) MP + 50 mg quercetin/kg; (v) MP + 40 μg alendronate/kg + 50 mg quercetin/kg; (vi) MP + 150 mg quercetin/kg; and (vii) MP + 40 μg alendronate/kg + 150 mg quercetin/kg. MP and alendronate were injected subcutaneously and quercetin was administered by oral gavage 3 days a week. At the end of the study, femur breaking strength was significantly decreased as a consequence of MP injection. This decrease was completely compensated for in groups receiving 50 mg quercetin/kg plus alendronate, and 150 mg quercetin/kg with or without alendronate. Quercetin noticeably elevated osteocalcin as a bone formation marker, while alendronate did not show such an effect. In addition, administration of 150 mg quercetin/kg increased femoral trabecular and cortical thickness by 36% and 22%, respectively, compared with the MP-treated group. These data suggest that 150 mg quercetin/kg, alone or in combination with alendronate, can completely prevent GIO through its bone formation stimulatory effect. PMID:23656499

  4. 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.

  5. 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

  6. Comparison between the effects of quercetin on seizure threshold in acute and chronic seizure models.

    PubMed

    Nassiri-Asl, Marjan; Hajiali, Farid; Taghiloo, Mina; Abbasi, Esmail; Mohseni, Fatemeh; Yousefi, Farbod

    2016-05-01

    Flavonoids are important constituents of food and beverages, and several studies have shown that they have neuroactive properties. Many of these compounds are ligands for γ-aminobutyric acid type A receptors in the central nervous system. This study aimed to investigate the anticonvulsant effects of quercetin (3,3',4',5,7-pentahydroxyflavone), which is a flavonoid found in plants, in rats treated with pentylenetetrazole in acute and chronic seizure models. Single intraperitoneal administration of quercetin did not show anticonvulsive effects against acute seizure. Similarly, multiple oral pretreatment with quercetin did not have protective effects against acute seizure. However, multiple intraperitoneal administration of quercetin (25 and 50 mg/kg) significantly increased time to death compared with the control (p < 0.001). However, quercetin pretreatment had no significant effects on the pattern of convulsion development during all periods of kindling. But on the test day, quercetin (100 mg/kg) could significantly increase generalized tonic-clonic seizure onset (GTCS) and decrease GTCS duration compared with the control (p < 0.01, p < 0.05). We conclude that quercetin has a narrow therapeutic dose range for anticonvulsant activities in vivo, and it has different effects on the seizure threshold. The different effects of quercetin on seizure threshold may occur through several mechanisms. PMID:24442347

  7. 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.

  8. The effect of quercetin phase II metabolism on its MRP1 and MRP2 inhibiting potential.

    PubMed

    van Zanden, Jelmer J; van der Woude, Hester; Vaessen, Judith; Usta, Mustafa; Wortelboer, Heleen M; Cnubben, Nicole H P; Rietjens, Ivonne M C M

    2007-07-15

    The present study characterises the effect of phase II metabolism, especially methylation and glucuronidation, of the model flavonoid quercetin on its capacity to inhibit human MRP1 and MRP2 activity in Sf9 inside-out vesicles. The results obtained reveal that 3'-O-methylation does not affect the MRP inhibitory potential of quercetin. However, 4'-O-methylation appeared to reduce the potential to inhibit both MRP1 and MRP2. In contrast, glucuronidation in general, and especially glucuronidation at the 7-hydroxylmoiety, resulting in 7-O-glucuronosyl quercetin, significantly increased the potential of quercetin to inhibit MRP1 and MRP2 mediated calcein transport with inhibition of MRP1 being generally more effective than that of MRP2. Overall, the results of this study reveal that the major phase II metabolites of quercetin are equally potent or even better inhibitors of human MRP1 and MRP2 than quercetin itself. This finding indicates that phase II metabolism of quercetin could enhance the potential use of quercetin- or flavonoids in general-as an inhibitor to overcome MRP-mediated multidrug resistance. PMID:17509533

  9. Effects of quercetin on the proliferation of breast cancer cells and expression of survivin in vitro

    PubMed Central

    DENG, XIAO-HUI; SONG, HAI-YAN; ZHOU, YING-FENG; YUAN, GUO-YAN; ZHENG, FENG-JIN

    2013-01-01

    Quercetin is a hydrophobic agent with potential anticancer activity. The aim of the present study was to observe the effects of quercetin on the proliferation of the breast cancer cell line MCF-7 and the gene expression of survivin. The molecular mechanism underlying the antiproliferative effect of quercetin was also investigated. MCF-7 breast cancer cells were treated with various concentrations of quercetin. The inhibitory effect of quercetin on proliferation was detected using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method and the inhibition rate was calculated. Cellular apoptosis was detected by immunocytochemistry and survivin mRNA expression levels were observed using reverse transcription-polymerase chain reaction (RT-PCR). Western blot analysis was used to analyze changes in the expression levels of survivin protein. Quercetin induced the apoptosis of MCF-7 cells and inhibited the proliferation of the MCF-7 breast cancer cells in a time- and concentration-dependent manner. The mRNA and protein expression levels of survivin were reduced as the concentration of quercetin increased. Quercetin inhibited the growth of MCF-7 cells and promoted apoptosis by inducing G0/ G1 phase arrest. It also regulated the expression of survivin mRNA in MCF-7 cells, which may be the mechanism underlying its antitumor effect. PMID:24223637

  10. Dermal quercetin smartCrystals®: Formulation development, antioxidant activity and cellular safety.

    PubMed

    Hatahet, T; Morille, M; Hommoss, A; Dorandeu, C; Müller, R H; Bégu, S

    2016-05-01

    Flavonoids are natural plant pigments, which possess high antioxidative and antiradical activities. However, their poor water solubility led to a limited bioavailability. To overcome this major hurdle, quercetin nanocrystals were produced implementing smartCrystals® technology. This process combines bead milling and subsequent high-pressure homogenization at relatively low pressure (300bar). To test the possibility to develop a dermal formulation from quercetin smartCrystals®, quercetin nanosuspensions were admixed to Lutrol® F127 and hydroxythylcellulose nonionic gels. The physicochemical properties (morphology, size and charge), saturation solubility, dissolution velocity and the antioxidant properties (DPPH assay) as well as the cellular interaction of the produced quercetin smartCrystals® were studied and compared to crude quercetin powder. Quercetin smartCrystals® showed a strong increase in the saturation solubility and the dissolution velocity (7.6 fold). SmartCrystals® loaded or not into gels proved to be physically stable over a period of three months at 25°C. Interestingly, in vitro DPPH assay confirmed the preservation of quercetin antioxidative properties after nanonization. In parallel, the nanocrystalline form did not display cellular toxicity, even at high concentration (50μg/ml), as assayed on an epithelial cell line (VERO cells). In addition, the nanocrystalline form confirmed a protective activity for VERO cells against hydrogen peroxide induced toxicity in vitro. This new formulation presents a promising approach to deliver quercetin efficiently to skin in well-tolerated formulations. PMID:26948977

  11. Quercetin 3-O-glucoside suppresses epidermal growth factor-induced migration by inhibiting EGFR signaling in pancreatic cancer cells.

    PubMed

    Lee, Jungwhoi; Han, Song-I; Yun, Jeong-Hun; Kim, Jae Hoon

    2015-12-01

    Pancreatic cancer is one of the most dangerous cancers and is associated with a grave prognosis. Despite increased knowledge of the complex signaling networks responsible for progression of pancreatic cancer, many challenging therapies have fallen short of expectations. In this study, we examined the anti-migratory effect of quercetin 3-O-glucoside in epidermal growth factor-induced cell migration by inhibiting EGF receptor (EGFR) signaling in several human pancreatic cancer cell lines. Treatment with quercetin, quercetin 3-O-glucoside, and quercetin 7-O-glucoside differentially suppressed epidermal growth factor-induced migration activity of human pancreatic cancer cells. In particular, quercetin 3-O-glucoside strongly inhibited the infiltration activity of pancreatic cancer cells in a dose-dependent manner. Furthermore, quercetin 3-O-glucoside exerted the anti-migratory effect even at a relatively low dose compared with other forms of quercetin. The anti-tumor effects of quercetin 3-O-glucoside were mediated by selectively inhibiting the EGFR-mediated FAK, AKT, MEK1/2, and ERK1/2 signaling pathway. Combinatorial treatment with quercetin 3-O-glucoside plus gemcitabine showed the synergistic anti-migratory effect on epidermal growth factor-induced cell migration in human pancreatic cancer cell lines. These results suggest that quercetin 3-O-glucoside has potential for anti-metastatic therapy in human pancreatic cancer. PMID:26109002

  12. 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

  13. 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.

  14. 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. PMID:24464737

  15. Quercetin: a pleiotropic kinase inhibitor against cancer.

    PubMed

    Russo, Gian Luigi; Russo, Maria; Spagnuolo, Carmela; Tedesco, Idolo; Bilotto, Stefania; Iannitti, Roberta; Palumbo, Rosanna

    2014-01-01

    Increased consumption of fruits and vegetables can represent an easy strategy to significantly reduce the incidence of cancer. From this observation, derived mostly from epidemiological data, the new field of chemoprevention has emerged in the primary and secondary prevention of cancer. Chemoprevention is defined as the use of natural or synthetic compounds able to stop, reverse, or delay the process of tumorigenesis in its early stages. A large number of phytochemicals are potentially capable of simultaneously inhibiting and modulating several key factors regulating cell proliferation in cancer cells. Quercetin is a flavonoid possessing potential chemopreventive properties. It is a functionally pleiotropic molecule, possessing multiple intracellular targets, affecting different cell signaling processes usually altered in cancer cells, with limited toxicity on normal cells. Simultaneously targeting multiple pathways may help to kill malignant cells and slow down the onset of drug resistance. Among the different substrates triggered by quercetin, we have reviewed the ability of the molecule to inhibit protein kinases involved in deregulated cell growth in cancer cells. PMID:24114481

  16. Reactive Oxygen Species Production and Mitochondrial Dysfunction Contribute to Quercetin Induced Death in Leishmania amazonensis

    PubMed Central

    Fonseca-Silva, Fernanda; Inacio, Job D. F.; Canto-Cavalheiro, Marilene M.; Almeida-Amaral, Elmo Eduardo

    2011-01-01

    Background Leishmaniasis, a parasitic disease caused by protozoa of the genus Leishmania, affects more than 12 million people worldwide. Quercetin has generated considerable interest as a pharmaceutical compound with a wide range of therapeutic activities. One such activity is exhibited against the bloodstream parasite Trypanosoma brucei and amastigotes of Leishmania donovani. However, the mechanism of protozoan action of quercetin has not been studied. Methodology/Principal Findings In the present study, we report here the mechanism for the antileishmanial activity of quercetin against Leishmania amazonensis promastigotes. Quercetin inhibited L. amazonensis promastigote growth in a dose- and time- dependent manner beginning at 48 hours of treatment and with maximum growth inhibition observed at 96 hours. The IC50 for quercetin at 48 hours was 31.4 µM. Quercetin increased ROS generation in a dose-dependent manner after 48 hours of treatment. The antioxidant GSH and NAC each significantly reduced quercetin-induced cell death. In addition, quercetin caused mitochondrial dysfunction due to collapse of mitochondrial membrane potential. Conclusions/Significance The effects of several drugs that interfere directly with mitochondrial physiology in parasites such as Leishmania have been described. The unique mitochondrial features of Leishmania make this organelle an ideal drug target while minimizing toxicity. Quercetin has been described as a pro-oxidant, generating ROS which are responsible for cell death in some cancer cells. Mitochondrial membrane potential loss can be brought about by ROS added directly in vitro or induced by chemical agents. Taken together, our results demonstrate that quercetin eventually exerts its antileishmanial effect on L. amazonensis promastigotes due to the generation of ROS and disrupted parasite mitochondrial function. PMID:21346801

  17. Quercetin enhances the antitumor activity of trichostatin A through upregulation of p53 protein expression in vitro and in vivo.

    PubMed

    Chan, Shu-Ting; Yang, Nae-Cherng; Huang, Chin-Shiu; Liao, Jiunn-Wang; Yeh, Shu-Lan

    2013-01-01

    This study investigated the effects of quercetin on the anti-tumor effect of trichostatin A (TSA), a novel anticancer drug, in vitro and in vivo and the possible mechanisms of these effects in human lung cancer cells. We first showed that quercetin (5 µM) significantly increased the growth arrest and apoptosis in A549 cells (expressing wild-type p53) induced by 25 ng/mL of (82.5 nM) TSA at 48 h by about 25% and 101%, respectively. However, such enhancing effects of quercetin (5 µM) were not significant in TSA-exposed H1299 cells (a p53 null mutant) or were much lower than in A549 cells. In addition, quercetin significantly increased TSA-induced p53 expression in A549 cells. Transfection of p53 siRNA into A549 cells significantly but not completely diminished the enhancing effects of quercetin on TSA-induced apoptosis. Furthermore, we demonstrated that quercetin enhanced TSA-induced apoptosis through the mitochondrial pathway. Transfection of p53 siRNA abolished such enhancing effects of quercetin. However, quercetin increased the acetylation of histones H3 and H4 induced by TSA in A549 cells, even with p53 siRNA transfection as well as in H1299 cells. In a xenograft mouse model of lung cancer, quercetin enhanced the antitumor effect of TSA. Tumors from mice treated with TSA in combination with quercetin had higher p53 and apoptosis levels than did those from control and TSA-treated mice. These data indicate that regulation of the expression of p53 by quercetin plays an important role in enhancing TSA-induced apoptosis in A549 cells. However, p53-independent mechanisms may also contribute to the enhancing effect of quercetin. PMID:23342112

  18. 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

  19. 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. PMID:20303338

  20. The effects of quercetin dietary supplementation on broiler growth performance, meat quality, and oxidative stability.

    PubMed

    Goliomytis, M; Tsoureki, D; Simitzis, P E; Charismiadou, M A; Hager-Theodorides, A L; Deligeorgis, S G

    2014-08-01

    The present study was conducted to describe the effects of quercetin dietary supplementation, at levels of 0.5 and 1 g/kg of feed, on growth performance, internal organ weights, meat quality, and meat oxidative stability during storage of broiler chickens reared from hatching to 42 d of age. Body weight and cumulative feed intake were not affected by quercetin supplementation (P > 0.05). However, poorer feed conversion ratio values were obtained with increasing levels of dietary quercetin (P-linear < 0.05). Relative heart weight was significantly higher for chickens that were given quercetin in comparison with the controls (P < 0.05). The rest of the internal organ weights measured (liver, spleen, and fat pad) and meat quality traits were not affected by dietary supplementation with quercetin, except for meat lightness and redness. Meat oxidative stability, expressed as nanograms of malondialdehyde per gram of meat, was improved (P < 0.05) during refrigerated storage for 3 and 9 d, when birds were fed quercetin at a level of 1 g/kg of feed. It is concluded that the incorporation of quercetin in broiler diets could prolong meat shelf life by reducing the rate of lipid oxidation, and increase relative heart weight, potentially contributing to improved animal health. PMID:24894531

  1. New Approach for Treatment of Primary Liver Tumors: The Role of Quercetin.

    PubMed

    Brito, Ana Filipa; Ribeiro, Marina; Abrantes, Ana Margarida; Mamede, Ana Catarina; Laranjo, Mafalda; Casalta-Lopes, João Eduardo; Gonçalves, Ana Cristina; Sarmento-Ribeiro, Ana Bela; Tralhão, José Guilherme; Botelho, Maria Filomena

    2016-01-01

    Hepatocellular carcinoma (HCC) is the most common primary liver tumor (PLT), with cholangiocarcinoma (CC) being the second most frequent. Glucose transporter 1 (GLUT-1) expression is increased in PLTs and therefore it is suggested as a therapeutic target. Flavonoids, like quercetin, are GLUT-1 competitive inhibitors and may be considered as potential therapeutic agents for PLTs. The objective of this study was evaluation of quercetin anticancer activity in three human HCC cell lines (HepG2, HuH7, and Hep3B2.1-7) and in a human CC cell line (TFK-1). The possible synergistic effect between quercetin and sorafenib, a nonspecific multikinase inhibitor used in clinical practice in patients with advanced HCC, was also evaluated. It was found that in all the cell lines, quercetin induced inhibition of the metabolic activity and cell death by apoptosis, followed by increase in BAX/BCL-2 ratio. Treatment with quercetin caused DNA damage in HepG2, Hep3B2.1-7, and TFK-1 cell lines. The effect of quercetin appears to be independent of P53. Incubation with quercetin induced an increase in GLUT-1 membrane expression and a consequent reduction in the cytoplasmic fraction, observed as a decrease in (18)F-FDG uptake, indicating a GLUT-1 competitive inhibition. The occurrence of synergy when sorafenib and quercetin were added simultaneously to HCC cell lines was noticed. Thus, the use of quercetin seems to be a promising approach for PLTs through GLUT-1 competitive inhibition. PMID:26943884

  2. 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

  3. Transient Landscape Response to Increased Coupling Across a Subduction Zone Interface, Talamanca Range, Costa Rica

    NASA Astrophysics Data System (ADS)

    Sitchler, J. C.; Kirby, E.; Fisher, D. M.

    2006-12-01

    , incised lower reach by a convex knickpoint. Hillslope gradients mimic this pattern, in that the landscape above knickpoints is characterized by low topographic relief. Knickpoints throughout the range are confined to a fairly narrow elevation range clustered around 2000 m, well below the ice extent of the last glacial maximum, and a preliminary analysis suggests that they are not strongly influenced by mapped lithologic differences. The uniform elevation distribution leads us to infer that these knickpoints define a mobile boundary between predominately low-gradient relict landscapes in the upper reaches of streams and relatively high-gradient (on the order of 2 to 3 times steeper) landscape in the lower reaches of the CT that is adjusting to a new (higher) incision rate. These initial observations are consistent with a simple model of a step-function increase in regional uplift rate, and subsequent transient fluvial response to the relative base level change. Downstream projection of the relict fluvial profiles suggests 1-1.5 km of incision, which we infer to represent rock uplift since the collision of the CR at ca. 1-2 Ma. Ongoing research is focused on accounting for evolving orographic precipitation and spatial patterns of rock uplift. However, our preliminary results indicate that the Talamanca range have experienced significant surface uplift at their crest as a consequence of subduction of the Cocos Ridge.

  4. 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

  5. Quercetin interaction with the chloroplast ATPase complex.

    PubMed

    Shoshan, V; Shahak, Y; Shavit, N

    1980-07-01

    1. Quercetin, a flavonoid which acts as an energy transfer inhibitor in photophosphorylation is shown to inhibit the P-ATP exchange activity of membrane-bound CF1 and the ATPase activity of isolated CF1. Quercetin, affects also the proton uptake in chloroplasts in a manner similar to that of dicyclohexylcarbodiimide. 2. The light-dependent proton uptake in EDTA-treated chloroplasts is stimulated by quercetin. In untreated chloroplasts quercetin has a dual effect: it enhances at pH above 7.5 while at lower pH values it decreases the extent of H+ uptake. Similar effects were obtained with dicyclohexylcarbodiimide. 3. Like quercetin, dicyclohexylcarbodiimide was also found to inhibit the ATPase activity of isolated CF1. 4. Quercetin inhibits uncoupled electron transport induced by either EDTA-treatment of chloroplasts or by addition of uncouplers. Quercetin restores H+ uptake in both types of uncoupled chloroplasts. 5. The mode of action of quercetin and dicyclohexylcarbodiimide in photophosphorylation is discussed, and interaction with both CF1 and F0 is suggested. PMID:6446936

  6. 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. PMID:26041228

  7. 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

  8. Anxiety and cognitive effects of quercetin liposomes in rats.

    PubMed

    Priprem, Aroonsri; Watanatorn, Jintanaporn; Sutthiparinyanont, Saengrawee; Phachonpai, Wathita; Muchimapura, Supaporn

    2008-03-01

    Quercetin, an effective flavonol used as an antioxidant, was investigated for its anxiolytic and cognitive activities in male Wistar rats. Oral quercetin (300 mg/kg body weight/day) was compared with oral and intranasal quercetin liposomes (20 microg/day). Quercetin liposomes, in a mixture of egg phosphatidylcholine, cholesterol, and quercetin (2:1:1) and dispersed in 50% polyethylene glycol in water, were approximately 200 nm in mean particle diameter and negative surface charge with a range of encapsulation efficiency of 60% to 80%. Anxiolytic and cognitive-enhancing effects of quercetin, conventional and liposomal, were subjected to elevated plus maze and Morris water maze tests, respectively. Both conventional and quercetin liposomes showed anxiolytic and cognitive-enhancing effects. A lower dose and a faster rate were observed with intranasal quercetin liposomes when compared with oral quercetin, conventional and liposomal. The intranasal quercetin liposomes are effective in the delivery of quercetin to the central nervous system. PMID:18249157

  9. 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

  10. 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

  11. 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. PMID:24472037

  12. Quercetin and its principal metabolites, but not myricetin, oppose lipopolysaccharide-induced hyporesponsiveness of the porcine isolated coronary artery

    PubMed Central

    Al-Shalmani, Salmin; Suri, Sunita; Hughes, David A; Kroon, Paul A; Needs, Paul W; Taylor, Moira A; Tribolo, Sandra; Wilson, Vincent G

    2011-01-01

    BACKGROUND AND PURPOSE Quercetin is anti-inflammatory in macrophages by inhibiting lipopolysaccharide (LPS)-mediated increases in cytokine and nitric oxide production but there is little information regarding the corresponding effect on the vasculature. We have examined the effect of quercetin, and its principal human metabolites, on inflammatory changes in the porcine isolated coronary artery. EXPERIMENTAL APPROACH Porcine coronary artery segments were incubated overnight at 37°C in modified Krebs-Henseleit solution with or without 1 µg·mL−1 LPS. Some segments were also co-incubated with quercetin-related flavonoids or Bay 11-7082, an inhibitor of NFκB. Changes in isometric tension of segments to vasoconstrictor and vasodilator agents were recorded. Nitrite content of the incubation solution was estimated using the Griess reaction, while inducible nitric oxide synthase was identified immunohistochemically. KEY RESULTS Lipopolysaccharide reduced, by 35–50%, maximal contractions to KCl and U46619, thromboxane A2 receptor agonist, and impaired endothelium-dependent relaxations to substance P. Nitrite content of the incubation medium increased 3- to 10-fold following exposure to LPS and inducible nitric oxide synthase was detected in the adventitia. Quercetin (0.1–10 µM) opposed LPS-induced changes in vascular responses, nitrite production and expression of inducible nitric oxide synthase. Similarly, 10 µM Bay 11-7082, 10 µM quercetin 3′-sulphate and 10 µM quercetin 3-glucuronide prevented LPS-induced changes, while myricetin (10 µM) was inactive. Myricetin (10 µM) prevented quercetin-induced modulation of LPS-mediated nitrite production. CONCLUSION AND IMPLICATIONS Quercetin, quercetin 3′-suphate and quercetin 3-glucuronide, exerted anti-inflammatory effects on the vasculature, possibly through a mechanism involving inhibition of NFκB. Myricetin-induced antagonism of the effect of anti-inflammatory action of quercetin merits further investigation

  13. Short-Term Increases in Transient Receptor Potential Vanilloid-1 Mediate Stress-Induced Enhancement of Neuronal Excitation

    PubMed Central

    Weitlauf, Carl; Ward, Nicholas J.; Lambert, Wendi S.; Sidorova, Tatiana N.; Ho, Karen W.; Sappington, Rebecca M.

    2014-01-01

    Progression of neurodegeneration in disease and injury is influenced by the response of individual neurons to stressful stimuli and whether this response includes mechanisms to counter declining function. Transient receptor potential (TRP) cation channels transduce a variety of disease-relevant stimuli and can mediate diverse stress-dependent changes in physiology, both presynaptic and postsynaptic. Recently, we demonstrated that knock-out or pharmacological inhibition of the TRP vanilloid-1 (TRPV1) capsaicin-sensitive subunit accelerates degeneration of retinal ganglion cell neurons and their axons with elevated ocular pressure, the critical stressor in the most common optic neuropathy, glaucoma. Here we probed the mechanism of the influence of TRPV1 on ganglion cell survival in mouse models of glaucoma. We found that induced elevations of ocular pressure increased TRPV1 in ganglion cells and its colocalization at excitatory synapses to their dendrites, whereas chronic elevation progressively increased ganglion cell Trpv1 mRNA. Enhanced TRPV1 expression in ganglion cells was transient and supported a reversal of the effect of TRPV1 on ganglion cells from hyperpolarizing to depolarizing, which was also transient. Short-term enhancement of TRPV1-mediated activity led to a delayed increase in axonal spontaneous excitation that was absent in ganglion cells from Trpv1−/− retina. In isolated ganglion cells, pharmacologically activated TRPV1 mobilized to discrete nodes along ganglion cell dendrites that corresponded to sites of elevated Ca2+. These results suggest that TRPV1 may promote retinal ganglion cell survival through transient enhancement of local excitation and axonal activity in response to ocular stress. PMID:25392504

  14. Short-term increases in transient receptor potential vanilloid-1 mediate stress-induced enhancement of neuronal excitation.

    PubMed

    Weitlauf, Carl; Ward, Nicholas J; Lambert, Wendi S; Sidorova, Tatiana N; Ho, Karen W; Sappington, Rebecca M; Calkins, David J

    2014-11-12

    Progression of neurodegeneration in disease and injury is influenced by the response of individual neurons to stressful stimuli and whether this response includes mechanisms to counter declining function. Transient receptor potential (TRP) cation channels transduce a variety of disease-relevant stimuli and can mediate diverse stress-dependent changes in physiology, both presynaptic and postsynaptic. Recently, we demonstrated that knock-out or pharmacological inhibition of the TRP vanilloid-1 (TRPV1) capsaicin-sensitive subunit accelerates degeneration of retinal ganglion cell neurons and their axons with elevated ocular pressure, the critical stressor in the most common optic neuropathy, glaucoma. Here we probed the mechanism of the influence of TRPV1 on ganglion cell survival in mouse models of glaucoma. We found that induced elevations of ocular pressure increased TRPV1 in ganglion cells and its colocalization at excitatory synapses to their dendrites, whereas chronic elevation progressively increased ganglion cell Trpv1 mRNA. Enhanced TRPV1 expression in ganglion cells was transient and supported a reversal of the effect of TRPV1 on ganglion cells from hyperpolarizing to depolarizing, which was also transient. Short-term enhancement of TRPV1-mediated activity led to a delayed increase in axonal spontaneous excitation that was absent in ganglion cells from Trpv1(-/-) retina. In isolated ganglion cells, pharmacologically activated TRPV1 mobilized to discrete nodes along ganglion cell dendrites that corresponded to sites of elevated Ca(2+). These results suggest that TRPV1 may promote retinal ganglion cell survival through transient enhancement of local excitation and axonal activity in response to ocular stress. PMID:25392504

  15. 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.

  16. Increased osteopontin and liver stiffness measurement by transient elastography in biliary atresia

    PubMed Central

    Honsawek, Sittisak; Chayanupatkul, Maneerat; Chongsrisawat, Voranush; Vejchapipat, Paisarn; Poovorawan, Yong

    2010-01-01

    AIM: To analyze plasma osteopontin levels and liver stiffness using transient elastography in postoperative biliary atresia (BA) children compared with healthy controls. METHODS: Thirty children with postoperative BA and 10 normal controls were enrolled. The patients were categorized into two groups according to their jaundice status. Plasma levels of osteopontin were determined using commercially available enzyme-linked immunosorbent assay. Liver stiffness was measured by using transient elastography (Fibroscan). Ten validated Fibroscan measurements were performed in each patient and control with the result expressed in kilopascals (kPa). RESULTS: Plasma osteopontin was significantly elevated in BA children compared with that of healthy controls (47.0 ± 56.4 ng/mL vs 15.1 ± 15.0 ng/mL, P = 0.01). The liver stiffness measurement was markedly elevated in the patients with BA compared with that of controls (26.9 ± 24.6 kPa vs 3.9 ± 0.7 kPa, P = 0.001). Subgroup analysis showed that the BA patients with jaundice had more pronounced plasma osteopontin levels than those without jaundice (87.1 ± 61.6 ng/mL vs 11.9 ± 6.1 ng/mL, P = 0.001). Furthermore, the mean liver stiffness was significantly greater in the jaundiced BA patients compared with non-jaundiced patients (47.7 ± 21.8 kPa vs 8.7 ± 3.0 kPa, P = 0.001). Additionally, plasma osteopontin was positively related to serum total bilirubin (r = 0.64, P < 0.001). There was also a correlation between plasma osteopontin and liver stiffness values (r = 0.60, P < 0.001). CONCLUSION: High plasma osteopontin positively correlated with degree of hepatic fibrosis and could be used as a biochemical parameter reflecting disease severity in postoperative BA children. PMID:21086566

  17. 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

  18. 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. PMID:25722169

  19. Effect of quercetine on survival and morphological properties of cultured embryonic rat spinal motoneurones.

    PubMed

    Ternaux, Jean-Pierre; Portalier, Paule

    2002-10-25

    Quercetine a flavonoid compound present in many plants and in the extract of Ginkgo biloba was shown to enhance the survival of purified rat spinal embryonic motoneurones, sampled at day embryonic 15 and maintained in culture for several days. Survival of embryonic spinal motoneurones is dose dependent and concentrations of quercetine ranging from 1 to 10 microM increase by 25% the number of living motoneurones in the culture. Excepted a slight significant decrease in the number of branches at day 3 and a small reduction of total neuritic length, no drastic changes in the motoneurones morphologies were observed in presence of quercetine. Results are discussed in term of neuronal protective effect of quercetine. PMID:12377378

  20. 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.

  1. 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.

  2. Quercetin protects against high glucose-induced damage in bone marrow-derived endothelial progenitor cells.

    PubMed

    Zhao, Li-Rong; Du, Yu-Jun; Chen, Lei; Liu, Zhi-Gang; Pan, Yue-Hai; Liu, Jian-Feng; Liu, Bin

    2014-10-01

    Endothelial progenitor cells (EPCs), a group of bone marrow-derived pro-angiogenic cells, contribute to vascular repair after damage. EPC dysfunction exists in diabetes and results in poor wound healing in diabetic patients with trauma or surgery. The aim of the present study was to determine the effect of quercetin, a natural flavonoid on high glucose‑induced damage in EPCs. Treatment with high glucose (40 mM) decreased cell viability and migration, and increased oxidant stress, as was evidenced by the elevated levels of reactive oxygen species (ROS), malondialdehyde (MDA) and superoxide dismutase in bone marrow-derived EPCs. Moreover, high glucose reduced the levels of endothelial nitric oxide synthase (eNOS) phosphorylation, nitric oxide (NO) production and intracellular cyclic guanosine monophosphate (cGMP). Quercetin supplement protected against high glucose‑induced impairment in cell viability, migration, oxidant stress, eNOS phosphorylation, NO production and cGMP levels. Quercetin also increased Sirt1 expression in EPCs. Inhibition of Sirt1 by a chemical antagonist sirtinol abolished the protective effect of quercetin on eNOS phosphorylation, NO production and cGMP levels following high glucose stress. To the best of our knowledge, the results provide the first evidence that quercetin protects against high glucose‑induced damage by inducing Sirt1-dependent eNOS upregulation in EPCs, and suggest that quercetin is a promising therapeutic agent for diabetic patients undergoing surgery or other invasive procedures. PMID:25197782

  3. Quercetin ameliorates glucose and lipid metabolism and improves antioxidant status in postnatally monosodium glutamate-induced metabolic alterations.

    PubMed

    Seiva, Fábio R F; Chuffa, Luiz Gustavo A; Braga, Camila Pereira; Amorim, João Paulo A; Fernandes, Ana Angélica H

    2012-10-01

    We reported the effects of quercetin on metabolic and hormonal profile as well as serum antioxidant activities in a model of MSG (monosodium glutamate)-induced obesity. Rats were divided into 4 groups: MSG group, submitted to neonatal treatment with high doses of MSG, administrated subcutaneously during 10 days, from 2 day-old; control groups, which received the same volume of saline. After completing 30 day-old, these groups were subdivided into 4 groups: control and MSG groups treated and non-treated with quercetin at doses of 75 mg/kg body weight (i.p.) over 42 days. BW gain and food consumption were higher in MSG treated rats and quercetin significantly reduced BW by 25%. While MSG increased triacylglycerol, total cholesterol and fractions, and reduced HDL concentrations, administration of quercetin normalized HDL-cholesterol and reduced others lipids. Insulin, leptin, glucose and creatinine levels were raised in MSG-treated rats and reduced after quercetin treatment. Alanine transaminase, aspartate transaminase, lactate dehydrogenase and alkaline phosphatase activities were lower after MSG-quercetin combination compared to rats given only MSG. MSG-quercetin combination augmented total protein and urea levels as well as glutathione peroxidase and superoxide dismutase activities in contrast to MSG-treated animals. Quercetin normalized serum lipid and glucose profile and minimized the MSG-related toxic effects, which was associated to its antioxidant properties. PMID:22809473

  4. Investigation of quercetin-induced HepG2 cell apoptosis-associated cellular biophysical alterations by atomic force microscopy.

    PubMed

    Pi, Jiang; Li, Baole; Tu, Lvying; Zhu, Haiyan; Jin, Hua; Yang, Fen; Bai, Haihua; Cai, Huaihong; Cai, Jiye

    2016-03-01

    Quercetin, a wildly distributed bioflavonoid, has been proved to possess excellent antitumor activity on hepatocellular carcinoma (HCC). In the present study, the biophysical properties of HepG2 cells were qualitatively and quantitatively determined using high resolution atomic force microscopy (AFM) to understand the anticancer effects of quercetin on HCC cells at nanoscale. The results showed that quercetin could induce severe apoptosis in HepG2 cells through arrest of cell cycle and disruption of mitochondria membrane potential. Additionally, the nuclei and F-actin structures of HepG2 cells were destroyed by quercetin treatment as well. AFM morphological data showed some typical apoptotic characterization of HepG2 cells with increased particle size and roughness in the ultrastructure of cell surface upon quercetin treatment. As an important biophysical property of cells, the membrane stiffness of HepG2 cells was further quantified by AFM force measurements, which indicated that HepG2 cells became much stiffer after quercetin treatment. These results collectively suggest that quercetin can be served as a potential therapeutic agent for HCC, which not only extends our understanding of the anticancer effects of quercetin against HCC cells into nanoscale, but also highlights the applications of AFM for the investigation of anticancer drugs. SCANNING 38:100-112, 2016. © 2015 Wiley Periodicals, Inc. PMID:26179807

  5. 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

  6. 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. PMID:24246038

  7. Quercetin, a flavonoid antioxidant, modulates endothelium-derived nitric oxide bioavailability in diabetic rat aortas.

    PubMed

    Machha, Ajay; Achike, Francis I; Mustafa, Ali Mohd; Mustafa, Mohd Rais

    2007-06-01

    The present work examined the effect of chronic oral administration of quercetin, a flavonoid antioxidant, on blood glucose, vascular function and oxidative stress in STZ-induced diabetic rats. Male Wistar-Kyoto (WKY) rats were randomized into euglycemic, untreated diabetic, vehicle (1% w/v methylcellulose)-treated diabetic, which served as control, or quercetin (10mgkg(-1) body weight)-treated diabetic groups and treated orally for 6 weeks. Quercetin treatment reduced blood glucose level in diabetic rats. Impaired relaxations to endothelium-dependent vasodilator acetylcholine (ACh) and enhanced vasoconstriction responses to alpha(1)-adrenoceptor agonist phenylephrine (PE) in diabetic rat aortic rings were restored to euglycemic levels by quercetin treatment. Pretreatment with N(omega)-nitro-l-arginine methyl ester (l-NAME, 10microM) or methylene blue (10microM) completely blocked but indomethacin (10microM) did not affect relaxations to ACh in aortic rings from vehicle- or quercetin-treated diabetic rats. PE-induced vasoconstriction with an essentially similar magnitude in vehicle- or quercetin-treated diabetic rat aortic rings pretreated with l-NAME (10microM) plus indomethacin (10microM). Quercetin treatment reduced plasma malonaldehyde (MDA) plus 4-hydroxyalkenals (4-HNE) content as well as increased superoxide dismutase activity and total antioxidant capacity in diabetic rats. From the present study, it can be concluded that quercetin administration to diabetic rats restores vascular function, probably through enhancement in the bioavailability of endothelium-derived nitric oxide coupled to reduced blood glucose level and oxidative stress. PMID:17513143

  8. 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.

  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. PMID:23644882

  10. Quercetin-Induced Cell Death in Human Papillary Thyroid Cancer (B-CPAP) Cells

    PubMed Central

    Mutlu Altundağ, Ergül; Kasacı, Tolga; Yılmaz, Ayşe Mine; Karademir, Betül; Koçtürk, Semra; Taga, Yavuz; Yalçın, A. Süha

    2016-01-01

    In this study, we have investigated the antiproliferative effect of quercetin on human papillary thyroid cancer cells and determined the apoptotic mechanisms underlying its actions. We have used different concentrations of quercetin to induce apoptosis and measured cell viability. Apoptosis and cell cycle analysis was determined by flow cytometry using Annexin V and propidium iodide. Finally, we have measured changes in caspase-3 and cleaved poly(ADP-ribose) polymerase (PARP) protein expression levels as hallmarks of apoptosis and Hsp90 protein expression level as a marker of proteasome activity in treated and control cells. Quercetin treatment of human papillary thyroid cancer cells resulted in decreased cell proliferation and increased rate of apoptosis by caspase activation. Furthermore, it was demonstrated that quercetin induces cancer cell apoptosis by downregulating the levels of Hsp90. In conclusion, we have shown that quercetin induces downregulation of Hsp90 expression that may be involved in the decrease of chymotrypsin-like proteasome activity which, in order, induces inhibition of growth and causes cell death in thyroid cancer cells. Thus, quercetin appears to be a promising candidate drug for Hsp90 downregulation and apoptosis of thyroid cancer cells. PMID:27057371

  11. 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

  12. 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

  13. 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…

  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. 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

  16. 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

  17. Microsomal Quercetin Glucuronidation in Rat Small Intestine Depends on Age and Segment

    PubMed Central

    Bolling, Bradley W.; Court, Michael H.; Blumberg, Jeffrey B.

    2011-01-01

    UDP-glucuronosyltransferase (UGT) activity toward the flavonoid quercetin and UGT protein were characterized in three equidistant small intestine (SI) segments from 4-, 12-, 18-, and 28-month-old male Fischer 344 rats (n = 8/age) using villin to control for enterocyte content. SI microsomal intrinsic clearance of quercetin was increased 3- to 9-fold from 4 months in the proximal and distal SI at 12 and 18 months. Likewise, at 30 μM quercetin, SI microsomal glucuronidation activity was increased with age: 4.8- and 3.9-fold greater at 18 months than at 4 months. Quercetin UGT regioselectivity was not changed by age. The distal SI preferentially catalyzed glucuronidation at the 7-position, whereas the proximal SI produced the greatest proportion of 4′- and 3′-conjugates. Enterocyte UGT content in different SI segments was not consistently changed with age. In the proximal SI, UGT1A increased 64 and 150% at 12 and 18 months and UGT1A1, UGT1A7, and UGT1A8 were also increased at 12 and 18 months. However, age-related changes in expression were inconsistent in the medial and distal segments. Microsomal rates of quercetin glucuronidation and UGT expression were positively correlated with UGT1A1 content for all pooled samples (r = 0.467) and at each age (r = 0.538–0.598). UGT1A7 was positively correlated with total, 7-O- and 3-O-quercetin glucuronidation at 18 months. Thus, age-related differences in UGT quercetin glucuronidation depend on intestinal segment, are more pronounced in the proximal and distal segments and may be partially related to UGT1A1 and UGT1A7 content. PMID:21543555

  18. 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.

  19. 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. PMID:26689735

  20. 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

  1. Transient and sustained increases in inositol 1,4,5-trisphosphate precede the differential growth response in gravistimulated maize pulvini

    NASA Technical Reports Server (NTRS)

    Perera, I. Y.; Heilmann, I.; Boss, W. F.; Davies, E. (Principal Investigator)

    1999-01-01

    The internodal maize pulvinus responds to gravistimulation with differential cell elongation on the lower side. As the site of both graviperception and response, the pulvinus is an ideal system to study how organisms sense changes in orientation. We observed a transient 5-fold increase in inositol 1,4,5-trisphosphate (IP3) within 10 s of gravistimulation in the lower half of the pulvinus, indicating that the positional change was sensed immediately. Over the first 30 min, rapid IP3 fluctuations were observed between the upper and lower halves. Maize plants require a presentation time of between 2 and 4 h before the cells on the lower side of the pulvinus are committed to elongation. After 2 h of gravistimulation, the lower half consistently had higher IP3, and IP3 levels on the lower side continued to increase up to approximately 5-fold over basal levels before visible growth. As bending became visible after 8-10 h, IP3 levels returned to basal values. Additionally, phosphatidylinositol 4-phosphate 5-kinase activity in the lower pulvinus half increased transiently within 10 min of gravistimulation, suggesting that the increased IP3 production was accompanied by an up-regulation of phosphatidylinositol 4, 5-bisphosphate biosynthesis. Neither IP3 levels nor phosphatidylinositol 4-phosphate 5-kinase activity changed in pulvini halves from vertical control plants. Our data indicate the involvement of IP3 and inositol phospholipids in both short- and long-term responses to gravistimulation. As a diffusible second messenger, IP3 provides a mechanism to transmit and amplify the signal from the perceiving to the responding cells in the pulvinus, coordinating a synchronized growth response.

  2. 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

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

    SciTech Connect

    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.

  4. 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

  5. Transient Overexpression of adh8a Increases Allyl Alcohol Toxicity in Zebrafish Embryos

    PubMed Central

    Klüver, Nils; Ortmann, Julia; Paschke, Heidrun; Renner, Patrick; Ritter, Axel P.; Scholz, Stefan

    2014-01-01

    Fish embryos are widely used as an alternative model to study toxicity in vertebrates. Due to their complexity, embryos are believed to more resemble an adult organism than in vitro cellular models. However, concerns have been raised with respect to the embryo's metabolic capacity. We recently identified allyl alcohol, an industrial chemical, to be several orders of magnitude less toxic to zebrafish embryo than to adult zebrafish (embryo LC50 = 478 mg/L vs. fish LC50 = 0.28 mg/L). Reports on mammals have indicated that allyl alcohol requires activation by alcohol dehydrogenases (Adh) to form the highly reactive and toxic metabolite acrolein, which shows similar toxicity in zebrafish embryos and adults. To identify if a limited metabolic capacity of embryos indeed can explain the low allyl alcohol sensitivity of zebrafish embryos, we compared the mRNA expression levels of Adh isoenzymes (adh5, adh8a, adh8b and adhfe1) during embryo development to that in adult fish. The greatest difference between embryo and adult fish was found for adh8a and adh8b expression. Therefore, we hypothesized that these genes might be required for allyl alcohol activation. Microinjection of adh8a, but not adh8b mRNA led to a significant increase of allyl alcohol toxicity in embryos similar to levels reported for adults (LC50 = 0.42 mg/L in adh8a mRNA-injected embryos). Furthermore, GC/MS analysis of adh8a-injected embryos indicated a significant decline of internal allyl alcohol concentrations from 0.23-58 ng/embryo to levels below the limit of detection (< 4.6 µg/L). Injection of neither adh8b nor gfp mRNA had an impact on internal allyl alcohol levels supporting that the increased allyl alcohol toxicity was mediated by an increase in its metabolization. These results underline the necessity to critically consider metabolic activation in the zebrafish embryo. As demonstrated here, mRNA injection is one useful approach to study the role of candidate enzymes involved in

  6. Transient overexpression of adh8a increases allyl alcohol toxicity in zebrafish embryos.

    PubMed

    Klüver, Nils; Ortmann, Julia; Paschke, Heidrun; Renner, Patrick; Ritter, Axel P; Scholz, Stefan

    2014-01-01

    Fish embryos are widely used as an alternative model to study toxicity in vertebrates. Due to their complexity, embryos are believed to more resemble an adult organism than in vitro cellular models. However, concerns have been raised with respect to the embryo's metabolic capacity. We recently identified allyl alcohol, an industrial chemical, to be several orders of magnitude less toxic to zebrafish embryo than to adult zebrafish (embryo LC50 = 478 mg/L vs. fish LC50 = 0.28 mg/L). Reports on mammals have indicated that allyl alcohol requires activation by alcohol dehydrogenases (Adh) to form the highly reactive and toxic metabolite acrolein, which shows similar toxicity in zebrafish embryos and adults. To identify if a limited metabolic capacity of embryos indeed can explain the low allyl alcohol sensitivity of zebrafish embryos, we compared the mRNA expression levels of Adh isoenzymes (adh5, adh8a, adh8b and adhfe1) during embryo development to that in adult fish. The greatest difference between embryo and adult fish was found for adh8a and adh8b expression. Therefore, we hypothesized that these genes might be required for allyl alcohol activation. Microinjection of adh8a, but not adh8b mRNA led to a significant increase of allyl alcohol toxicity in embryos similar to levels reported for adults (LC50 = 0.42 mg/L in adh8a mRNA-injected embryos). Furthermore, GC/MS analysis of adh8a-injected embryos indicated a significant decline of internal allyl alcohol concentrations from 0.23-58 ng/embryo to levels below the limit of detection (< 4.6 µg/L). Injection of neither adh8b nor gfp mRNA had an impact on internal allyl alcohol levels supporting that the increased allyl alcohol toxicity was mediated by an increase in its metabolization. These results underline the necessity to critically consider metabolic activation in the zebrafish embryo. As demonstrated here, mRNA injection is one useful approach to study the role of candidate enzymes involved in

  7. 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

  8. Quantification of transient increase of the blood–brain barrier permeability to macromolecules by optimized focused ultrasound combined with microbubbles

    PubMed Central

    Shi, Lingyan; Palacio-Mancheno, Paolo; Badami, Joseph; Shin, Da Wi; Zeng, Min; Cardoso, Luis; Tu, Raymond; Fu, Bingmei M

    2014-01-01

    Radioimmunotherapy using a radiolabeled monoclonal antibody that targets tumor cells has been shown to be efficient for the treatment of many malignant cancers, with reduced side effects. However, the blood–brain barrier (BBB) inhibits the transport of intravenous antibodies to tumors in the brain. Recent studies have demonstrated that focused ultrasound (FUS) combined with microbubbles (MBs) is a promising method to transiently disrupt the BBB for the drug delivery to the central nervous system. To find the optimal FUS and MBs that can induce reversible increase in the BBB permeability, we employed minimally invasive multiphoton microscopy to quantify the BBB permeability to dextran-155 kDa with similar molecular weight to an antibody by applying different doses of FUS in the presence of MBs with an optimal size and concentration. The cerebral microcirculation was observed through a section of frontoparietal bone thinned with a micro-grinder. About 5 minutes after applying the FUS on the thinned skull in the presence of MBs for 1 minute, TRITC (tetramethylrhodamine isothiocyanate)-dextran-155 kDa in 1% bovine serum albumin in mammalian Ringer’s solution was injected into the cerebral circulation via the ipsilateral carotid artery by a syringe pump. Simultaneously, the temporal images were collected from the brain parenchyma ~100–200 μm below the pia mater. Permeability was determined from the rate of tissue solute accumulation around individual microvessels. After several trials, we found the optimal dose of FUS. At the optimal dose, permeability increased by ~14-fold after 5 minutes post-FUS, and permeability returned to the control level after 25 minutes. FUS without MBs or MBs injected without FUS did not change the permeability. Our method provides an accurate in vivo assessment for the transient BBB permeability change under the treatment of FUS. The optimal FUS dose found for the reversible BBB permeability increase without BBB disruption is reliable

  9. 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

  10. 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.

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

    PubMed

    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

  12. 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

  13. 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

  14. Diabetic neuropathy: An evaluation of the use of quercetin in the cecum of rats

    PubMed Central

    Ferreira, Paulo Emilio Botura; Lopes, Cláudia Regina Pinheiro; Alves, Angela Maria Pereira; Alves, Éder Paulo Belato; Linden, David Robert; Zanoni, Jacqueline Nelisis; Buttow, Nilza Cristina

    2013-01-01

    AIM: To investigate the effect of quercetin supplementation on the myenteric neurons and glia in the cecum of diabetic rats. METHODS: Total preparations of the muscular tunic were prepared from the ceca of twenty-four rats divided into the following groups: control (C), control supplemented with quercetin (200 mg/kg quercetin body weight) (CQ), diabetic (D) and diabetic supplemented with quercetin (DQ). Immunohistochemical double staining technique was performed with HuC/D (general population)/nitric oxide synthase (nNOS), HuC-D/S-100 and VIP. Density analysis of the general neuronal population HuC/D-IR, the nNOS-IR (nitrergic subpopulation) and the enteric glial cells (S-100) was performed, and the morphometry and the reduction in varicosity population (VIP-IR) in these populations were analyzed. RESULTS: Diabetes promoted a significant reduction (25%) in the neuronal density of the HuC/D-IR (general population) and the nNOS-IR (nitrergic subpopulation) compared with the C group. Diabetes also significantly increased the areas of neurons, glial cells and VIP-IR varicosities. Supplementation with quercetin in the DQ group prevented neuronal loss in the general population and increased its area (P < 0.001) and the area of nitrergic subpopulation (P < 0.001), when compared to C group. Quercetin induced a VIP-IR and glial cells areas (P < 0.001) in DQ group when compared to C, CQ and D groups. CONCLUSION: In diabetes, quercetin exhibited a neuroprotective effect by maintaining the density of the general neuronal population but did not affect the density of the nNOS subpopulation. PMID:24151360

  15. One calcitriol dose transiently increases Helios+ FoxP3+ T cells and ameliorates autoimmune demyelinating disease.

    PubMed

    Nashold, Faye E; Nelson, Corwin D; Brown, Lauren M; Hayes, Colleen E

    2013-10-15

    Multiple sclerosis (MS) is an incurable inflammatory demyelinating disease. We investigated one calcitriol dose plus vitamin D3 (calcitriol/+D) as a demyelinating disease treatment in experimental autoimmune encephalomyelitis (EAE). Evidence that calcitriol-vitamin D receptor pathway deficits may promote MS, and data showing calcitriol enhancement of autoimmune T cell apoptosis provided the rationale. Whereas vitamin D3 alone was ineffective, calcitriol/+D transiently increased central nervous system (CNS) Helios(+)FoxP3(+) T cells and sustainably decreased CNS T cells, pathology, and neurological deficits in mice with EAE. Calcitriol/+D, which was more effective than methylprednisolone, has potential for reversing inflammatory demyelinating disease safely and cost-effectively. PMID:23968560

  16. MiR-351 transiently increases during muscle regeneration and promotes progenitor cell proliferation and survival upon differentiation.

    PubMed

    Chen, Yongxin; Melton, David W; Gelfond, Jonathan A L; McManus, Linda M; Shireman, Paula K

    2012-11-01

    MicroRNAs (miRNAs) regulate many biological processes including muscle development. However, little is known regarding miRNA regulation of muscle regeneration. Murine tibialis anterior muscle was evaluated after cardiotoxin-induced injury and used for global miRNA expression analysis. From day 1 through day 21 following injury, 298 miRNAs were significantly changed at least at one time point, including 86 miRNAs that were altered >10-fold compared with uninjured skeletal muscle. Temporal miRNA expression patterns included inflammation-related miRNAs (miR-223 and -147) that increased immediately after injury; this pattern contrasted to that of mature muscle-specific miRNAs (miR-1, -133a, and -499) that abruptly decreased following injury followed by upregulation in later regenerative events. Another cluster of miRNAs were transiently increased in the early days of muscle regeneration including miR-351, a miRNA that was also transiently expressed during myogenic progenitor cell (MPC) differentiation in vitro. Based on computational predictions, further studies demonstrated that E2f3 was a target of miR-351 in myoblasts. Moreover, knockdown of miR-351 expression inhibited MPC proliferation and promoted apoptosis during MPC differentiation, whereas miR-351 overexpression protected MPC from apoptosis during differentiation. Collectively, these observations suggest that miR-351 is involved in both the maintenance of MPC proliferation and the transition into differentiated myotubes. Thus, a novel, time-dependent sequence of molecular events during muscle regeneration has been identified; miR-351 inhibits E2f3 expression, a key regulator of cell cycle progression and proliferation, and promotes MPC proliferation and protects early differentiating MPC from apoptosis, important events in the hostile tissue environment after acute muscle injury. PMID:22968638

  17. MiR-351 transiently increases during muscle regeneration and promotes progenitor cell proliferation and survival upon differentiation

    PubMed Central

    Chen, Yongxin; Melton, David W.; Gelfond, Jonathan A. L.; McManus, Linda M.

    2012-01-01

    MicroRNAs (miRNAs) regulate many biological processes including muscle development. However, little is known regarding miRNA regulation of muscle regeneration. Murine tibialis anterior muscle was evaluated after cardiotoxin-induced injury and used for global miRNA expression analysis. From day 1 through day 21 following injury, 298 miRNAs were significantly changed at least at one time point, including 86 miRNAs that were altered >10-fold compared with uninjured skeletal muscle. Temporal miRNA expression patterns included inflammation-related miRNAs (miR-223 and -147) that increased immediately after injury; this pattern contrasted to that of mature muscle-specific miRNAs (miR-1, -133a, and -499) that abruptly decreased following injury followed by upregulation in later regenerative events. Another cluster of miRNAs were transiently increased in the early days of muscle regeneration including miR-351, a miRNA that was also transiently expressed during myogenic progenitor cell (MPC) differentiation in vitro. Based on computational predictions, further studies demonstrated that E2f3 was a target of miR-351 in myoblasts. Moreover, knockdown of miR-351 expression inhibited MPC proliferation and promoted apoptosis during MPC differentiation, whereas miR-351 overexpression protected MPC from apoptosis during differentiation. Collectively, these observations suggest that miR-351 is involved in both the maintenance of MPC proliferation and the transition into differentiated myotubes. Thus, a novel, time-dependent sequence of molecular events during muscle regeneration has been identified; miR-351 inhibits E2f3 expression, a key regulator of cell cycle progression and proliferation, and promotes MPC proliferation and protects early differentiating MPC from apoptosis, important events in the hostile tissue environment after acute muscle injury. PMID:22968638

  18. 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. PMID:26103093

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

    PubMed

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

    2016-03-01

    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 flavonoidin 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 firstdemonstrated the interaction between quercetin and the VDR at the molecular level by using fluorecence 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

  20. 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

  1. 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

  2. Inactivated Parapoxvirus ovis induces a transient increase in the expression of proinflammatory, Th1-related, and autoregulatory cytokines in mice

    PubMed Central

    Anziliero, D.; Weiblen, R.; Kreutz, L.C.; Spilki, F.; Flores, E.F.

    2014-01-01

    The immunostimulatory properties of inactivated Parapoxvirus ovis (iPPVO) have long been investigated in different animal species and experimental settings. In this study, we investigated the effects of iPPVO on cytokine expression in mice after intraperitoneal inoculation. Spleen and sera collected from iPPVO-treated mice at intervals after inoculation were submitted to cytokine mRNA determination by real-time PCR (qPCR), serum protein concentration by ELISA, and interferon (IFN)-α/β activity by bioassay. The spleen of iPPVO-treated animals showed a significant increase in mRNA expression of all cytokines assayed, with different kinetics and magnitude. Proinflammatory cytokines interleukin (IL)-1β, tumor necrosis factor-alpha (TNF-α), and IL-8 mRNA peaked at 24 hours postinoculation (hpi; 5.4-fold increase) and 48 hpi (3- and 10-fold increases), respectively. A 15-fold increase in IFN-γ and 6-fold IL-12 mRNA increase were detected at 48 and 24 hpi, respectively. Increased expression of autoregulatory cytokines (Th2), mainly IL-10 and IL-4, could be detected at later times (72 and 96 hpi) with peaks of 4.7- and 4.9-fold increases, respectively. IFN-I antiviral activity against encephalomyocarditis virus was demonstrated in sera of treated animals between 6 and 12 hpi, with a >90% reduction in the number of plaques. Measurement of serum proteins by ELISA revealed increased levels of IL-1, TNF-α, IL-12, IFN-γ, and IL-10, with kinetics similar to those observed by qPCR, especially for IL-12 and IFN-γ. These data demonstrate that iPPVO induced a transient and complex cytokine response, initially represented by Th1-related cytokines followed by autoregulatory and Th2 cytokines. PMID:24519126

  3. High glucose modifies transient receptor potential canonical type 6 channels via increased oxidative stress and syndecan-4 in human podocytes.

    PubMed

    Thilo, Florian; Lee, Marlene; Xia, Shengqiang; Zakrzewicz, Andreas; Tepel, Martin

    2014-07-18

    Transient receptor potential canonical (TRPC) channels type 6 play an important role in the function of human podocytes. Diabetic nephropathy is characterized by altered TRPC6 expression and functions of podocytes. Thus, we hypothesized that high glucose modifies TRPC6 channels via increased oxidative stress and syndecan-4 (SDC-4) in human podocytes. Human podocytes were exposed to control conditions (5.6 mmol/L D-glucose), high glucose (30 mmol/L D-glucose or L-glucose), 100 μmol/L peroxynitrite, or high glucose and the superoxide dismutase mimetic tempol (100 μmol/L). TRPC6 and SDC-4 transcripts and protein expression were measured using RT-PCR and in-cell Western assay. Intracellular reactive oxygen species (ROS) and cytosolic calcium were measured using fluorescent dye techniques. High D-glucose increased TRPC6 transcripts to 8.66±4.08 (p<0.05) and TRPC6 protein expression to 1.44±0.07 (p<0.05) without altering SDC-4 transcripts or protein expression. The D-glucose induced increase of TRPC6 expression was blocked by tempol. Increased oxidative stress using peroxynitrite significantly increased TRPC6 transcripts to 4.29±1.26 (p<0.05) and TRPC6 protein expression to 1.28±0.05 (p<0.05) without altering SDC-4 transcripts or protein expression. In human podocytes transfected with scrambled siRNA, high D-glucose increased ROS after 90 min to 3.55±0.08 arbitrary units while 5.6 mmol/L D-glucose increased ROS to 2.49±0.09 (p<0.001) only. The increase in ROS was inhibited by tempol and by SDC-4 knockdown. High glucose modifies TRPC6 channels and ROS production via SDC-4 in human podocytes. PMID:24942878

  4. Possible use of quercetin, an antioxidant, for protection of cells suffering from overload of intracellular Ca2+: a model experiment.

    PubMed

    Sakanashi, Yoko; Oyama, Keisuke; Matsui, Hiroko; Oyama, Toshihisa B; Oyama, Tomohiro M; Nishimura, Yumiko; Sakai, Hitomi; Oyama, Yasuo

    2008-08-01

    Quercetin is known to protect the cells suffering from oxidative stress. The oxidative stress elevates intracellular Ca(2+) concentration, one of the phenomena responsible for cell death. Therefore, we hypothesized that quercetin would protect the cells suffering from overload of intracellular Ca(2+). To test the hypothesis, the effects of quercetin on the cells suffering from oxidative stress and intracellular Ca(2+) overload were examined by using a flow cytometer with appropriate fluorescence probes (propidium iodide, fluo-3-AM, and annexin V-FITC) and rat thymocytes. The concentrations (1-30 microM) of quercetin to protect the cells suffering from intracellular Ca(2+) overload by A23187, a calcium ionophore, were similar to those for the cells suffering from oxidative stress by H(2)O(2). The cell death respectively induced by H(2)O(2) and A23187 was significantly suppressed by removal of external Ca(2+). Furthermore, quercetin greatly delayed the process of Ca(2+)-dependent cell death although it did not significantly affect the elevation of intracellular Ca(2+) concentration by H(2)O(2) and A23187, respectively. It is concluded that quercetin can protect the cells from oxidative injury in spite of increased concentration of intracellular Ca(2+). Results suggest that quercetin is also used for protection of cells suffering from overload of intracellular Ca(2+). PMID:18586279

  5. Quercetin downregulates Mcl-1 by acting on mRNA stability and protein degradation

    PubMed Central

    Spagnuolo, C; Cerella, C; Russo, M; Chateauvieux, S; Diederich, M; Russo, G L

    2011-01-01

    Background: We recently demonstrated that quercetin, a flavonoid naturally present in food and beverages belonging to the large class of phytochemicals, was able to sensitise leukaemic cells isolated from patients with chronic lymphocytic leukaemia (CLL) when associated with recombinant tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) or anti-CD95. We also showed that quercetin potentiated the effect of fludarabine on resistant B cells from CLL patients. Resistance to therapy in CLL depends on the expression and activity of anti-apoptotic proteins of the Bcl-2 family. Among these, myeloid cell leukaemia-1 (Mcl-1) has been associated with apoptotic resistance in CLL. Therefore, we investigate here whether the sensitising activity of this flavonoid, which leads to increased apoptosis in both cell lines and CLL, could be related to Mcl-1 expression and stability. Results: B cells isolated from CLL patients showed different levels of Mcl-1 protein expression, resulting, in several cases, in increased sensitivity to fludarabine. Quercetin significantly enhanced the downregulation of Mcl-1 in B cells isolated from selected patients expressing detectable levels of Mcl-1. In U-937 cells, quercetin increased Mcl-1 mRNA instability in the presence of actinomycin D. When cells were treated with MG-132, a proteasome inhibitor, Mcl-1 protein level increased. However, quercetin, in the presence of Z-Vad-FMK, continued to lower Mcl-1 protein expression, indicating its independence from caspase-mediated degradation. In contrast, co-treatment of quercetin and MG-132 did not revert the effect of MG-132 mono-treatment, thus suggesting a possible interference of quercetin in regulating the proteasome-dependent degradation of Mcl-1. Gossypol, a small-molecule inhibitor of Bcl-2 family members, mimics the activity of quercetin by lowering Mcl-1 expression and sensitising U-937 cells to apoptosis induced by recombinant TRAIL and the Fas-ligand. Conclusion: This study

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

    PubMed

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

    2016-07-01

    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

  7. 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

  8. Quercetin attenuates neuronal death against aluminum-induced neurodegeneration in the rat hippocampus.

    PubMed

    Sharma, D R; Wani, W Y; Sunkaria, A; Kandimalla, R J; Sharma, R K; Verma, D; Bal, A; Gill, K D

    2016-06-01

    Aluminum is a light weight and toxic metal present ubiquitously on earth, which has gained considerable attention due to its neurotoxic effects. It also has been linked ecologically and epidemiologically to several neurological disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), Guamanian-Parkinsonian complex and Amyotrophic lateral sclerosis (ALS). The mechanism of aluminum neurotoxicity is poorly understood, but it is well documented that aluminum generates reactive oxygen species (ROS). Enhanced ROS production leads to disruption of cellular antioxidant defense systems and release of cytochrome c (cyt-c) from mitochondria to cytosol resulting in apoptotic cell death. Quercetin (a natural flavonoid) protects it from oxidative damage and has been shown to decrease mitochondrial damage in various animal models of oxidative stress. We hypothesized that if oxidative damage to mitochondria does play a significant role in aluminum-induced neurodegeneration, and then quercetin should ameliorate neuronal apoptosis. Administration of quercetin (10mg/kg body wt/day) reduced aluminum (10mg/kg body wt/day)-induced oxidative stress (decreased ROS production, increased mitochondrial superoxide dismutase (MnSOD) activity). In addition, quercetin also prevents aluminum-induced translocation of cyt-c, and up-regulates Bcl-2, down-regulates Bax, p53, caspase-3 activation and reduces DNA fragmentation. Quercetin also obstructs aluminum-induced neurodegenerative changes in aluminum-treated rats as seen by Hematoxylin and Eosin (H&E) staining. Further electron microscopic studies revealed that quercetin attenuates aluminum-induced mitochondrial swelling, loss of cristae and chromatin condensation. These results indicate that treatment with quercetin may represent a therapeutic strategy to attenuate the neuronal death against aluminum-induced neurodegeneration. PMID:26944603

  9. Quercetin Aglycone Is Bioavailable in Murine Pancreas and Pancreatic Xenografts

    PubMed Central

    Zhang, Lifeng; Angst, Eliane; Park, Jenny L.; Moro, Aune; Dawson, David W.; Reber, Howard A.; Eibl, Guido; Hines, O. Joe; Go, Vay-Liang W.; Lu, Qing-Yi

    2010-01-01

    Quercetin is a potential chemopreventive and chemotherapeutic agent for pancreatic and other cancers. This study was to examine the distribution of quercetin in plasma, lung, liver, pancreas and pancreatic cancer xenografts in a murine in vivo model and the uptake of quercetin in pancreatic cancer MiaPaCa-2 cells in cellular in vitro model. Mice were randomly allocated to control diet, 0.2 and 1% quercetin diet groups utilizing the AIN93G-based diet (n=12 per group) for 6 weeks. In addition, 6 mice from each group were injected weekly with chemotherapeutic drug gemcitabine (120 mg/kg mouse, i.p.). MiaPaCa cells were collected from culture medium after cells were exposed to 30 µM of quercetin for 0.5, 1, 2, 4, 8, and 24 hrs. Levels of quercetin and 3-O’-methyl-quercetin in mice tissues and MiaPaCa-2 cells were measured by high-pressure liquid chromatography following enzymatic hydrolysis and then extraction. Our study showed that quercetin is accumulated in pancreatic cancer cells, and is absorbed in the circulating system, tumors and tissues of pancreas, liver and lung in vivo. A higher proportion of total quercetin found in tumors and pancreas are aglycones. Gemcitabine co-treatment with quercetin reduced absorption of quercetin in mice circulatory system and liver. Results from the study provide important information on the interpretation of chemo-therapeutic efficacy of quercetin. PMID:20499918

  10. Physiological increases in lactate inhibit intracellular calcium transients, acidify myocytes and decrease force in term pregnant rat myometrium.

    PubMed

    Hanley, Jacqui-Ann; Weeks, Andrew; Wray, Susan

    2015-10-15

    Lactate is increased in myometrial capillary blood from women in slow or non-progressive labour (dystocia), suggesting that it is detrimental to uterine contractions. There are, however, no studies of the effect of lactate on the myometrium. We therefore investigated its effects and mechanism of action on myometrial strips from term pregnant rats. The effects on spontaneous and oxytocin-induced contractility in response to sodium lactate and other weak acids (1-20 mM) were studied. In some experiments, simultaneous force and intracellular Ca(2+) or pH (pH(i)) were measured with Indo-1 or Carboxy-SNARF, respectively. Statistical differences were tested using non-parametric tests. Lactate significantly decreased spontaneous contractility with an EC50 of 3.9 mM. Propionate, butyrate and pyruvate also reduced contractions with similar potency. The effects of lactate were reduced in the presence of oxytocin but remained significant. Lactate decreased pH(i) and nulling the decrease in pH(i) abolished its effects. We also show that lactate inhibited Ca(2+) transients, with these changes mirroring those produced on force. If Ca(2+) entry was enhanced by depolarization (high KCl) or applying the Ca(2+) channel agonist, Bay K 4644, the effects of lactate were abolished. Taken together, these data show that lactate in the physiological range potently decreases myometrial contractility as a result of its inhibition of Ca(2+) transients, which can be attributed to the induced acidification. The present study suggests that the accumulation of extracellular lactate will reduce myometrial contractions and could therefore contribute to labour dystocia. PMID:26223765

  11. 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

  12. Quercetin inhibits human breast cancer cell proliferation and induces apoptosis via Bcl-2 and Bax regulation.

    PubMed

    Duo, Jian; Ying, Guo-Guang; Wang, Guo-Wen; Zhang, Li

    2012-06-01

    Breast cancer is a disease in which cancer cells form in the tissues of the breast. The present study aimed to explore the effect of the flavonoid compound quercetin on the growth and apoptosis of human breast cancer cells. Varying concentrations (12.5, 25, 50, 100, 200 µM) of quercetin were applied to cultured MCF-7 human breast cancer cells for defined lengths of time. At 50 to 200 µM doses, quercetin significantly inhibited the proliferation of MCF-7 cells assessed by MTT colorimetry, in both dose- and time-dependent manners (P<0.05). The compound also increased apoptosis after 48 h of exposure (P<0.05). Furthermore, following quercetin treatment Bcl-2 expression decreased significantly while Bax expression increased significantly (P<0.05). In brief, quercetin inhibits cell growth and induces apoptosis in MCF-7 human breast cancer cells. The mechanisms behind these effects may stem from the downregulation of Bcl-2 protein expression and upregulation of Bax expression. PMID:22447039

  13. Repeated transient mRNA bursts precede increases in transcriptional and mitochondrial proteins during training in human skeletal muscle

    PubMed Central

    Perry, Christopher G R; Lally, James; Holloway, Graham P; Heigenhauser, George J F; Bonen, Arend; Spriet, Lawrence L

    2010-01-01

    Exercise training induces mitochondrial biogenesis, but the time course of molecular sequelae that accompany repetitive training stimuli remains to be determined in human skeletal muscle. Therefore, throughout a seven-session, high-intensity interval training period that increased (12%), we examined the time course of responses of (a) mitochondrial biogenesis and fusion and fission proteins, and (b) selected transcriptional and mitochondrial mRNAs and proteins in human muscle. Muscle biopsies were obtained 4 and 24 h after the 1st, 3rd, 5th and 7th training session. PGC-1α mRNA was increased >10-fold 4 h after the 1st session and returned to control within 24 h. This ‘saw-tooth’ pattern continued until the 7th bout, with smaller increases after each bout. In contrast, PGC-1α protein was increased 24 h after the 1st bout (23%) and plateaued at +30–40% between the 3rd and 7th bout. Increases in PGC-1β mRNA and protein were more delayed and smaller, and did not persist. Distinct patterns of increases were observed in peroxisome proliferator-activated receptor (PPAR) α and γ protein (1 session), PPAR β/δ mRNA and protein (5 sessions) and nuclear respiratory factor-2 protein (3 sessions) while no changes occurred in mitochondrial transcription factor A protein. Citrate synthase (CS) and β-HAD mRNA were rapidly increased (1 session), followed 2 sessions later (session 3) by increases in CS and β-HAD activities, and mitochondrial DNA. Changes in COX-IV mRNA (session 3) and protein (session 5) were more delayed. Training also increased mitochondrial fission proteins (fission protein-1, >2-fold; dynamin-related protein-1, 47%) and the fusion protein mitofusin-1 (35%) but not mitofusin-2. This study has provided the following novel information: (a) the training-induced increases in transcriptional and mitochondrial proteins appear to result from the cumulative effects of transient bursts in their mRNAs, (b) training-induced mitochondrial biogenesis appears to

  14. Absence of initiating activity by quercetin in the rat liver.

    PubMed

    Kato, K; Mori, H; Tanaka, T; Fujii, M; Kawai, T; Nishikawa, A; Takahashi, M; Hirono, I

    1985-08-01

    Initiating activity of quercetin was tested in rats which were treated with partial hepatectomy and given a liver cancer promoter, phenobarbital. A few intestinal neoplasms were seen but without significant difference in incidence from those in the quercetin-untreated group. Moreover, neither neoplastic nor preneoplastic liver changes were detected in quercetin-treated groups. With hepatocyte primary culture/DNA repair test, quercetin did not produce genotoxicity. The results show that quercetin has no initiating or genotoxic activities in the rat liver. PMID:4029060

  15. 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

  16. Biological impacts of resveratrol, quercetin, and N-acetylcysteine on oxidative stress in human gingival fibroblasts.

    PubMed

    Orihuela-Campos, Rita Cristina; Tamaki, Naofumi; Mukai, Rie; Fukui, Makoto; Miki, Kaname; Terao, Junji; Ito, Hiro-O

    2015-05-01

    In periodontitis, production of reactive oxygen species (ROS) by neutrophils induces oxidative stress and deteriorates surrounding tissues. Antioxidants reduce damage caused by ROS and are used to treat diseases involving oxidative stress. This study summarizes the different effects of resveratrol, quercetin, and N-acetylcysteine (NAC) on human gingival fibroblasts (HGFs) under oxidative stress induced by hydrogen peroxide. Real-time cytotoxicity analyses reveals that resveratrol and quercetin enhanced cell proliferation even under oxidative stress. Of the antioxidants tested, resveratrol is the most effective at inhibiting ROS production. HGFs incubated with resveratrol and quercetin up-regulate the transcription of type I collagen gene after 3 h, but only resveratrol sustained this up-regulation for 24 h. A measurement of the oxygen consumption rate (OCR, mitochondrial respiration) shows that resveratrol generates the highest maximal respiratory capacity, followed by quercetin and NAC. Simultaneous measurement of OCR and the extracellular acidification rate (non-mitochondrial respiration) reveals that resveratrol and quercetin induce an increase in mitochondrial respiration when compared with untreated cells. NAC treatment consumes less oxygen and enhances more non-mitochondrial respiration. In conclusion, resveratrol is the most effective antioxidant in terms of real-time cytotoxicity analysis, reduction of ROS production, and enhancement of type I collagen synthesis and mitochondrial respiration in HGFs. PMID:26060353

  17. Biological impacts of resveratrol, quercetin, and N-acetylcysteine on oxidative stress in human gingival fibroblasts

    PubMed Central

    Orihuela-Campos, Rita Cristina; Tamaki, Naofumi; Mukai, Rie; Fukui, Makoto; Miki, Kaname; Terao, Junji; Ito, Hiro-O

    2015-01-01

    In periodontitis, production of reactive oxygen species (ROS) by neutrophils induces oxidative stress and deteriorates surrounding tissues. Antioxidants reduce damage caused by ROS and are used to treat diseases involving oxidative stress. This study summarizes the different effects of resveratrol, quercetin, and N-acetylcysteine (NAC) on human gingival fibroblasts (HGFs) under oxidative stress induced by hydrogen peroxide. Real-time cytotoxicity analyses reveals that resveratrol and quercetin enhanced cell proliferation even under oxidative stress. Of the antioxidants tested, resveratrol is the most effective at inhibiting ROS production. HGFs incubated with resveratrol and quercetin up-regulate the transcription of type I collagen gene after 3 h, but only resveratrol sustained this up-regulation for 24 h. A measurement of the oxygen consumption rate (OCR, mitochondrial respiration) shows that resveratrol generates the highest maximal respiratory capacity, followed by quercetin and NAC. Simultaneous measurement of OCR and the extracellular acidification rate (non-mitochondrial respiration) reveals that resveratrol and quercetin induce an increase in mitochondrial respiration when compared with untreated cells. NAC treatment consumes less oxygen and enhances more non-mitochondrial respiration. In conclusion, resveratrol is the most effective antioxidant in terms of real-time cytotoxicity analysis, reduction of ROS production, and enhancement of type I collagen synthesis and mitochondrial respiration in HGFs. PMID:26060353

  18. Quercetin Preventive Effects on Theophylline-Induced Anomalies in Rat Embryo

    PubMed Central

    Sistani Karampour, Neda; Arzi, Ardeshir; Najafzadeh Varzi, Hossein; Mohammadian, Babak; Rezaei, Mohsen

    2014-01-01

    Background: Theophylline has been shown to cause heart anomaly in animal and human fetus. Objectives: The present study aimed to investigate the protective effect of quercetin on theophylline-induced heart disorders in rat embryo. Materials and Methods: Theophylline-induced teratogenicity in rats was used as the animal model. Pregnant rats were administered theophylline (259 mg/kg, po) or theophylline plus quercetin (259 mg/kg, po and 100 mg/kg, ip, respectively) on 9th and 10th days of pregnancy. On day 19, cardiac changes were assessed, measuring malondialdehyde (MDA) and glutathione peroxidase (GPx) activity levels in blood samples and also the fetus heart weight. Histopathological examination was also performed on all specimens. Results: Theophylline-treated rats showed MDA level elevation and GPx activity reduction. Quercetin treatment improved heart conditions and resulted in a significant reduction in MDA levels and elevation in GPx activity. Moreover, co-administration of quercetin and theophylline increased the heart weight significantly. Furthermore, histophatological study showed no changes in the treated groups. Conclusions: This study demonstrated that quercetin have beneficial effects on theophylline-induced-anomalies in rat embryo. PMID:25237647

  19. 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. PMID:25892208

  20. Permeation and skin retention of quercetin from microemulsions containing Transcutol® P.

    PubMed

    Censi, Roberta; Martena, Valentina; Hoti, Ela; Malaj, Ledjan; Di Martino, Piera

    2012-09-01

    A microemulsion for the cutaneous release of quercetin was prepared. An aqueous phase, containing 40% Transcutol® P as solubilizing agent and permeation enhancer, was emulsified with Labrafil® as oil phase and Labrasol®/Capryol™ 90 as Solvent/Co-solvent. Quercetin was dissolved in the microemulsion at the concentration of 1%. Ternary phase diagrams were generated to determine the optimal concentration of each excipient composing the microemulsion. The physicochemical properties of the microemulsion, such as pH, viscosity, refractive index, and particle size distribution were determined. The microemulsion was stable for 12 months at the storing conditions of 25.0 ± 1.0°C. The in vitro quercetin permeability into and through the abdominal hairless pig skin was determined by vertical Franz's cells. Quercetin showed hardly any permeability through the skin when dissolved in water- and Transcutol® P-free media, whereas a remarkable increase in cutaneous permeability was observed when quercetin was formulated in the microemulsion or when simply dissolved in Transcutol® P. These two last formulations are those showing the lower skin retention. PMID:22188183

  1. 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

  2. The Flavonoid Quercetin Reverses Pulmonary Hypertension in Rats

    PubMed Central

    Moreno, Enrique; Moral-Sanz, Javier; Barreira, Bianca; Galindo, Pilar; Pandolfi, Rachele; Jimenez, Rosario; Moreno, Laura; Cogolludo, Angel; Duarte, Juan; Perez-Vizcaino, Francisco

    2014-01-01

    Quercetin is a dietary flavonoid which exerts vasodilator, antiplatelet and antiproliferative effects and reduces blood pressure, oxidative status and end-organ damage in humans and animal models of systemic hypertension. We hypothesized that oral quercetin treatment might be protective in a rat model of pulmonary arterial hypertension. Three weeks after injection of monocrotaline, quercetin (10 mg/kg/d per os) or vehicle was administered for 10 days to adult Wistar rats. Quercetin significantly reduced mortality. In surviving animals, quercetin decreased pulmonary arterial pressure, right ventricular hypertrophy and muscularization of small pulmonary arteries. Classic biomarkers of pulmonary arterial hypertension such as the downregulated expression of lung BMPR2, Kv1.5, Kv2.1, upregulated survivin, endothelial dysfunction and hyperresponsiveness to 5-HT were unaffected by quercetin. Quercetin significantly restored the decrease in Kv currents, the upregulation of 5-HT2A receptors and reduced the Akt and S6 phosphorylation. In vitro, quercetin induced pulmonary artery vasodilator effects, inhibited pulmonary artery smooth muscle cell proliferation and induced apoptosis. In conclusion, quercetin is partially protective in this rat model of PAH. It delayed mortality by lowering PAP, RVH and vascular remodeling. Quercetin exerted effective vasodilator effects in isolated PA, inhibited cell proliferation and induced apoptosis in PASMCs. These effects were associated with decreased 5-HT2A receptor expression and Akt and S6 phosphorylation and partially restored Kv currents. Therefore, quercetin could be useful in the treatment of PAH. PMID:25460361

  3. Synergistic neurotoxicity induced by methylmercury and quercetin in mice

    PubMed Central

    Martins, Roberta de P.; Braga, Hugo de C.; da Silva, Aline P.; Dalmarco, Juliana B.; de Bem, Andreza F.; dos Santos, Adair Roberto S.; Dafre, Alcir L.; Pizzolatti, Moacir G.; Latini, Alexandra; Aschner, Michael; Farina, Marcelo

    2010-01-01

    Methylmercury (MeHg) is a highly neurotoxic pollutant, whose mechanisms of toxicity are related to its pro-oxidative properties. A previous report showed under in vivo conditions the neuroprotective effects of plants of the genus Polygala against MeHg-induced neurotoxicity. Moreover, the flavonoid quercetin, isolated from Polygala sabulosa, displayed beneficial effects against MeHg-induced oxidative damage under in vitro conditions. In this study, we sought for potential beneficial effects of quercetin against the neurotoxicity induced by MeHg in Swiss female mice. Animals were divided into six experimental groups: control, quercetin low dose (5 mg/Kg), quercetin high dose (50 mg/Kg), MeHg (40 mg/L, in tap water), MeHg + quercetin low dose, and MeHg + quercetin high dose. After the treatment (21 days), a significant motor deficit was observed in MeHg + quercetin groups. Biochemical parameters related to oxidative stress showed that the simultaneous treatment with quercetin and MeHg caused a higher cerebellar oxidative damage when compared to the individual exposures. MeHg plus quercetin elicited a higher cerebellar lipid peroxidation than MeHg or quercetin alone. The present results indicate that under in vivo conditions quercetin and MeHg cause additive pro-oxidative effects toward the mice cerebellum and that such phenomenon is associated with the observed motor deficit. PMID:19141311

  4. Increase of uncertainty in transient climate response to cumulative carbon emissions after stabilization of atmospheric CO2 concentration

    NASA Astrophysics Data System (ADS)

    Tachiiri, Kaoru; Hajima, Tomohiro; Kawamiya, Michio

    2015-12-01

    We analyzed a dataset from an experiment of an earth system model of intermediate complexity, focusing on the change in transient climate response to cumulative carbon emissions (TCRE) after atmospheric CO2 concentration was stabilized in the Representative Concentration Pathway (RCP) 4.5. We estimated the TCRE in 2005 at 0.3-2.4 K/TtC for an unconstrained case and 1.1-1.7 K/TtC when constrained with historical and present-day observational data, the latter result being consistent with other studies. The range of TCRE increased when the increase of CO2 concentration was moderated and then stabilized. This is because the larger (smaller) TCRE members yield even greater (less) TCRE. An additional experiment to assess the equilibrium state revealed significant changes in temperature and cumulative carbon emissions after 2300. We also found that variation of land carbon uptake is significant to the total allowable carbon emissions and subsequent change of the TCRE. Additionally, in our experiment, we revealed that equilibrium climate sensitivity (ECS), one of the 12 parameters perturbed in the ensemble experiment, has a strong positive relationship with the TCRE at the beginning of the stabilization and its subsequent change. We confirmed that for participant models in the Coupled Model Intercomparison Project Phase 5, ECS has a strong positive relationship with TCRE. For models using similar experimental settings, there is a positive relationship with TCRE for the start of the period of stabilization in CO2 concentration, and rate of change after stabilization. The results of this study are influential regarding the total allowable carbon emissions calculated from the TCRE and the temperature increase set as the mitigation target.

  5. Quercetin treatment ameliorates inflammation and fibrosis in mice with nonalcoholic steatohepatitis.

    PubMed

    Marcolin, Eder; San-Miguel, Beatriz; Vallejo, Daniela; Tieppo, Juliana; Marroni, Norma; González-Gallego, Javier; Tuñón, María J

    2012-10-01

    We investigated whether quercetin protects from steatosis and limits the expression of proinflammatory and fibrogenic genes in C57BL/6J mice with nonalcoholic steatohepatitis (NASH) induced by feeding a methionine-choline-deficient (MCD) diet. Quercetin (50 mg/kg) was given by oral route daily. Mice were randomly divided into 4 groups that received for 2 or 4 wk: the control diet plus vehicle, control diet plus quercetin, MCD diet plus vehicle, and MCD diet plus quercetin. At both 2 and 4 wk, feeding the MCD diet resulted in liver steatosis, inflammatory cell accumulation, oxidative stress evaluated by the concentration of TBARS, and fibrosis evidenced by the staining of α-smooth muscle actin-positive cells in the liver. At both 2 and 4 wk, the MCD diet induced an increase in the mRNA levels of Il6, Tnf, Ptgs2, and Hmgb1 and increased the protein concentrations of Toll-like receptor-4, c-Jun terminal kinase, and p65 NFκB subunit compared with control rats. Feeding the mice the MCD diet also triggered an increase of Col1a1, Col3a1, Plod3, Tgfb1, Smad3, Smad7, Pdgfb, Ctgf, Areg, Mmp9, and Timp1 mRNA levels. These effects were totally or partially prevented by treatment with quercetin. The data obtained suggest that attenuation of multiple profibrotic and proinflammatory gene pathways contributes to the beneficial effects of quercetin in mice with MCD diet-induced steatohepatitis. PMID:22915297

  6. 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

  7. 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.

  8. Designing polymeric microparticulate drug delivery system for hydrophobic drug quercetin

    PubMed Central

    Hazra, Moumita; Dasgupta Mandal, Dalia; Mandal, Tamal; Bhuniya, Saikat; Ghosh, Mallika

    2015-01-01

    The aim of this study was to investigate pharmaceutical potentialities of a polymeric microparticulate drug delivery system for modulating the drug profile of poorly water-soluble quercetin. In this research work two cost effective polymers sodium alginate and chitosan were used for entrapping the model drug quercetin through ionic cross linking method. In vitro drug release, swelling index, drug entrapment efficiency, Fourier Transforms Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), X-ray Diffraction (XRD) and Differential Scanning Calorimetric (DSC) studies were also done for physicochemical characterization of the formulations. Swelling index and drug release study were done at a pH of 1.2, 6.8 and 7.4 to evaluate the GI mimetic action which entails that the swelling and release of the all the Formulation1 (F1), Formulation2 (F2) and Formulation3 (F3) at pH 1.2 were minimal confirming the prevention of drug release in the acidic environment of stomach. Comparatively more sustained release was seen from the formulations F2 & F3 at pH 6.8 and pH 7.4 after 7 h of drug release profiling. Drug entrapment efficiency of the formulations shows in F1 (D:C:A = 2:5:30) was approximately 70% whereas the increase in chitosan concentration in F2 (D:C:A = 2:10:30) has shown an entrapment efficiency of 81%. But the comparative further increase of chitosan concentration in F3 (D:C:A = 2:15:30) has shown a entrapment of 80% which is not having any remarkable difference from F2. The FTIR analysis of drug, polymers and the formulations indicated the compatibility of the drug with the polymers. The smoothness of microspheres in F2 & F3 was confirmed by Scanning Electron Microscopy (SEM). However F1 microsphere has shown more irregular shape comparatively. The DSC studies indicated the absence of drug-polymer interaction in the microspheres. Our XRD studies have revealed that when pure drug exhibits crystalline structure with less dissolution profile

  9. Interfering with ROS Metabolism in Cancer Cells: The Potential Role of Quercetin

    PubMed Central

    Gibellini, Lara; Pinti, Marcello; Nasi, Milena; De Biasi, Sara; Roat, Erika; Bertoncelli, Linda; Cossarizza, Andrea

    2010-01-01

    A main feature of cancer cells, when compared to normal ones, is a persistent pro-oxidative state that leads to an intrinsic oxidative stress. Cancer cells have higher levels of reactive oxygen species (ROS) than normal cells, and ROS are, in turn, responsible for the maintenance of the cancer phenotype. Persistent ROS stress may induce adaptive stress responses, enabling cancer cells to survive with high levels of ROS and maintain cellular viability. However, excessive ROS levels render cancer cells highly susceptible to quercetin, one of the main dietary flavonoids. Quercetin depletes intracellular glutathione and increases intracellular ROS to a level that can cause cell death. PMID:24281116

  10. 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.

  11. 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

  12. 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

  13. 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

  14. Quercetin induced apoptosis in association with death receptors and fludarabine in cells isolated from chronic lymphocytic leukaemia patients

    PubMed Central

    Russo, M; Spagnuolo, C; Volpe, S; Mupo, A; Tedesco, I; Russo, G-L

    2010-01-01

    Background: Quercetin is a flavonoid naturally present in food and beverages belonging to the large class of phytochemicals with potential anti-cancer properties. Here, we investigated the ability of quercetin to sensitise primary cells from chronic lymphocytic leukaemia (CLL) to death receptor (DR) agonists, recombinant TNF-related-apoptosis-inducing ligand (rTRAIL) and anti-CD95, and to fludarabine, a widely used chemotherapeutic drug against CLL. Methods: Peripheral white blood cells were isolated from patients and incubated with medium containing 50 ng ml anti-CD95 agonist antibody; 10 ng ml recombinant TRAIL; 10–25 μM quercetin and 3.5–14 μM fludarabine. Neutral Red assay was used to measure cell viability, where as apoptosis was assessed by determining caspase-3 activity, exposure to Annexin V and PARP fragmentation. Results: Quercetin significantly enhanced anti-CD95- and rTRAIL-induced cell death as shown by decreased cell viability, increased caspase-3 and -9 activities, and positivity to Annexin V. In addition, association of quercetin with fludarabine increases the apoptotic response in CLL cells of about two-fold compared with quercetin monotreatment. Conclusion: This work shows that resistance to DR- and fludarabine-induced cell death in leukaemic cells isolated from CLL patients can be ameliorated or bypassed by the combined treatment with quercetin. Considering the low toxicity of the molecule, our study results are in favour of a potential use of quercetin in adjuvant chemotherapy in combination with other drugs. PMID:20648016

  15. Quercetin protects primary human osteoblasts exposed to cigarette smoke through activation of the antioxidative enzymes HO-1 and SOD-1.

    PubMed

    Braun, Karl F; Ehnert, Sabrina; Freude, Thomas; Egaña, José T; Schenck, Thilo L; Buchholz, Arne; Schmitt, Andreas; Siebenlist, Sebastian; Schyschka, Lilianna; Neumaier, Markus; Stöckle, Ulrich; Nussler, Andreas K

    2011-01-01

    Smokers frequently suffer from impaired fracture healing often due to poor bone quality and stability. Cigarette smoking harms bone cells and their homeostasis by increased formation of reactive oxygen species (ROS). The aim of this study was to investigate whether Quercetin, a naturally occurring antioxidant, can protect osteoblasts from the toxic effects of smoking. Human osteoblasts exposed to cigarette smoke medium (CSM) rapidly produced ROS and their viability decreased concentration- and time-dependently. Co-, pre- and postincubation with Quercetin dose-dependently improved their viability. Quercetin increased the expression of the anti-oxidative enzymes heme-oxygenase- (HO-) 1 and superoxide-dismutase- (SOD-) 1. Inhibiting HO-1 activity abolished the protective effect of Quercetin. Our results demonstrate that CSM damages human osteoblasts by accumulation of ROS. Quercetin can diminish this damage by scavenging the radicals and by upregulating the expression of HO-1 and SOD-1. Thus, a dietary supplementation with Quercetin could improve bone matter, stability and even fracture healing in smokers. PMID:22203790

  16. 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

  17. 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

  18. Efficient entry of cell-penetrating peptide nona-arginine into adherent cells involves a transient increase in intracellular calcium

    PubMed Central

    Melikov, Kamran; Hara, Ann; Yamoah, Kwabena; Zaitseva, Elena; Zaitsev, Eugene; Chernomordik, Leonid V.

    2015-01-01

    Understanding the mechanism of entry of cationic peptides such as nona-arginine (R9) into cells remains an important challenge to their use as efficient drug-delivery vehicles. At nanomolar to low micromolar R9 concentrations and at physiological temperature, peptide entry involves endocytosis. In contrast, at a concentration ≥10 μM, R9 induces a very effective non-endocytic entry pathway specific for cationic peptides. We found that a similar entry pathway is induced at 1–2 μM concentrations of R9 if peptide application is accompanied by a rapid temperature drop to 15°C. Both at physiological and at sub-physiological temperatures, this entry mechanism was inhibited by depletion of the intracellular ATP pool. Intriguingly, we found that R9 at 10–20 μM and 37°C induces repetitive spikes in intracellular Ca2+ concentration. This Ca2+ signalling correlated with the efficiency of the peptide entry. Pre-loading cells with the Ca2+ chelator BAPTA (1,2-bis(o-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid) inhibited both Ca2+ spikes and peptide entry, suggesting that an increase in intracellular Ca2+ precedes and is required for peptide entry. One of the hallmarks of Ca2+ signalling is a transient cell-surface exposure of phosphatidylserine (PS), a lipid normally residing only in the inner leaflet of the plasma membrane. Blocking the accessible PS with the PS-binding domain of lactadherin strongly inhibited non-endocytic R9 entry, suggesting the importance of PS externalization in this process. To conclude, we uncovered a novel mechanistic link between calcium signalling and entry of cationic peptides. This finding will enhance our understanding of the properties of plasma membrane and guide development of future drug-delivery vehicles. PMID:26272944

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

    PubMed Central

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

    2013-01-01

    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 (Tmax), of 1 and 2 h and a mean maximum value concentration (Cmax), 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. PMID:25505566

  20. Metabonomic analysis of quercetin against the toxicity of chronic exposure to a mixture of four organophosphate pesticides in rat plasma.

    PubMed

    Cao, Can; Zeng, Yan; Shi, Haidan; Yang, Shuang; Bao, Wei; Qi, Lei; Liu, Ying; Zhao, Xiujun

    2016-09-01

    1. A metabonomics approach was performed to investigate the effect of quercetin on the toxicity of chronic exposure to a mixture of four organophosphate pesticides (OPs) at their corresponding no-observed-adverse-effect level (NOAEL). The rats were divided into six groups (n = 10/group): control, two different doses of quercetin, OPs mixture and different doses of quercetin plus OPs mixture-treated groups. 2. Nine metabolites, including two quercetin metabolites and seven endogenous metabolites were identified in plasma. The intensities of metabolites significantly changed in the OP mixture-treated group compared with the control group (p < 0.01), such as lysoPE (16:0/0:0), lysoPC (17:0/0:0), lysoPC (15:0/0:0) and 4-pyridoxic acid, significantly increased; by contrast, the intensities of arachidonic acid and citric acid significantly decreased. Anomalous intensity changes in aforementioned metabolites were alleviated in the OP mixture plus 50 mg/kgċbw/d quercetin-treated group compared with the OP mixture-treated group (p < 0.05). 3. The results indicated that quercetin elicited partial protective effects against the toxicity induced by a mixture of OPs, which include regulation of lipid metabolism, improvement of tricarboxylic acid (TCA) cycle disorders, enhancement of antioxidant defence system to protect the liver. PMID:26677787

  1. Protective Effect of Quercetin on Oxidative Stress in Glucose-6-Phosphate Dehydrogenase-Deficient Erythrocytes in Vitro

    PubMed Central

    Jamshidzadeh, Akram; Rezaeian Mehrabadi, Abbas

    2010-01-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficient subjects are vulnerable to oxidative stress. Quercetin, a flavonoids, has been employed as a potent oxygen-free radical scavenger in order to assess the protective effects of quercetin against H2O2-induced oxidative damage in G6PD-deficient and normal human erythrocytes. Erythrocytes of G6PD-deficient (n = 10) and normal (n = 10) subjects were incubated with different concentrations of quercetin. The produced thiobarbituric acid reactive substance (TBARS) and glutathione (GSH) level of erythrocytes were then subsequently measured. Different concentrations of quercetin showed no significant hemolysis, compared with the phosphate buffer solution. Upon challenge with H2O2, there was a significant (p < 0.005) decrease in GSH and an increase in TBARS level in G6PD-deficient erythrocytes. With quercetin, it managed to preserve concentrations of 15 to 75 mM preserved GSH and TBARS levels of normal and G6PD-deficient erythrocytes against H2O2-induced oxidative damage. In addition to its well-established antioxidant effects, quercetin was also found to have cytoprotective properties. PMID:24363724

  2. 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. PMID:26493151

  3. Quercetin induces caspase-dependent extrinsic apoptosis through inhibition of signal transducer and activator of transcription 3 signaling in HER2-overexpressing BT-474 breast cancer cells

    PubMed Central

    SEO, HYE-SOOK; KU, JIN MO; CHOI, HAN-SEOK; CHOI, YOUN KYUNG; WOO, JONG-KYU; KIM, MINSOO; KIM, ILHWAN; NA, CHANG HYEOK; HUR, HANSOL; JANG, BO-HYOUNG; SHIN, YONG CHEOL; KO, SEONG-GYU

    2016-01-01

    Flavonoids are assumed to exert beneficial effects in different types of cancers at high concentrations. Yet, their molecular mechanisms of action remain unknown. The present study aimed to examine the effect of quercetin on proliferation and apoptosis in HER2-expressing breast cancer cells. The anti-proliferative effects of quercetin were examined by proliferation, MTT and clonogenic survival assays. The effect of quercetin on expression of apoptotic molecules was determined by western blotting. Luciferase reporter assay was performed to measure signal transducer and activator of transcription 3 (STAT3) transcriptional activity. ELISA assay was performed to measure intracellular MMP-9 levels. Immunocytochemistry was performed to evaluate the nuclear STAT3 level. The results revealed that quercetin inhibited the proliferation of BT-474 cells in a dose- and time-dependent manner. Quercetin also inhibited clonogenic survival (anchorage-dependent and -independent) of BT-474 cells in a dose-dependent manner. These growth inhibitions were accompanied with an increase in sub-G0/G1 apoptotic populations. Quercetin induced caspase-dependent extrinsic apoptosis upregulating the levels of cleaved caspase-8 and cleaved caspase-3, and inducing the cleavage of poly(ADP-ribose) polymerase (PARP). In contrast, quercetin did not induce apoptosis via intrinsic mitochondrial apoptosis pathway since this compound did not decrease the mitochondrial membrane potential and did not affect the levels of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (BAX). Quercetin reduced the expression of phospho-JAK1 and phospho-STAT3 and decreased STAT3-dependent luciferase reporter gene activity in the BT-474 cells. Quercetin inhibited MMP-9 secretion and decreased the nuclear translocation of STAT3. Our study indicates that quercetin induces apoptosis at concentrations >20 µM through inhibition of STAT3 signaling and could serve as a useful compound to prevent or treat HER2

  4. 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

  5. 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.

  6. Quercetin induces caspase-dependent extrinsic apoptosis through inhibition of signal transducer and activator of transcription 3 signaling in HER2-overexpressing BT-474 breast cancer cells.

    PubMed

    Seo, Hye-Sook; Ku, Jin Mo; Choi, Han-Seok; Choi, Youn Kyung; Woo, Jong-Kyu; Kim, Minsoo; Kim, Ilhwan; Na, Chang Hyeok; Hur, Hansol; Jang, Bo-Hyoung; Shin, Yong Cheol; Ko, Seong-Gyu

    2016-07-01

    Flavonoids are assumed to exert beneficial effects in different types of cancers at high concentrations. Yet, their molecular mechanisms of action remain unknown. The present study aimed to examine the effect of quercetin on proliferation and apoptosis in HER2-expressing breast cancer cells. The anti-proliferative effects of quercetin were examined by proliferation, MTT and clonogenic survival assays. The effect of quercetin on expression of apoptotic molecules was determined by western blotting. Luciferase reporter assay was performed to measure signal transducer and activator of transcription 3 (STAT3) transcriptional activity. ELISA assay was performed to measure intracellular MMP-9 levels. Immunocytochemistry was performed to evaluate the nuclear STAT3 level. The results revealed that quercetin inhibited the proliferation of BT-474 cells in a dose- and time-dependent manner. Quercetin also inhibited clonogenic survival (anchorage-dependent and -independent) of BT-474 cells in a dose-dependent manner. These growth inhibitions were accompanied with an increase in sub-G0/G1 apoptotic populations. Quercetin induced caspase-dependent extrinsic apoptosis upregulating the levels of cleaved caspase-8 and cleaved caspase-3, and inducing the cleavage of poly(ADP‑ribose) polymerase (PARP). In contrast, quercetin did not induce apoptosis via intrinsic mitochondrial apoptosis pathway since this compound did not decrease the mitochondrial membrane potential and did not affect the levels of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (BAX). Quercetin reduced the expression of phospho-JAK1 and phospho-STAT3 and decreased STAT3-dependent luciferase reporter gene activity in the BT-474 cells. Quercetin inhibited MMP-9 secretion and decreased the nuclear translocation of STAT3. Our study indicates that quercetin induces apoptosis at concentrations >20 µM through inhibition of STAT3 signaling and could serve as a useful compound to prevent or treat HER2

  7. The sorption of quercetin by high-basicity anion exchangers

    NASA Astrophysics Data System (ADS)

    Udalova, N. A.; Karpov, S. I.; Selemenev, V. F.; Sharmar, I. A.

    2009-06-01

    The sorption of quercetin on anionites with various porosities in the OH- and Cl- forms was studied under static conditions. The equilibrium (distribution coefficients K p) and kinetic (effective diffusion coefficients D eff) parameters of quercetin sorption on AV-17-2P and AV-17-6M anionites in the Cl- and OH- forms were calculated. The mechanism of quercetin interactions with the anion exchangers was studied by electron microscopy and IR spectroscopy.

  8. Rutin and total quercetin content in amaranth (Amaranthus spp.).

    PubMed

    Kalinova, Jana; Dadakova, Eva

    2009-03-01

    The aim of the study was to confirm the presence of rutin, one of the most common quercetin glycosides, and other quercetin derivatives in plants of genus Amaranthus, to investigate the influence of the species and variety on rutin distribution in the plant and content changes during growing season. The rutin content was determined by micellar electrokinetic capillary chromatography in individual plant parts at the beginning of the growth, at the flowering stage and at the maturity stage of five Amaranthus species. The total quercetin content was determined by micellar electrokinetic capillary chromatography too. The rutin content in amaranth ranged from 0.08 (in seeds) to 24.5 g/kg dry matter (in leaves). Comparison of the determined total quercetin content and the calculated content of quercetin released from rutin did not prove important presence of quercetin or other quercetin derivatives than rutin. Only amaranth leaves sampled at the maturity stage probably contained quercetin or quercetin derivatives. Significant differences in the rutin content were established among species and as well varieties. Amaranthus hybrid and A. cruentus were the best sources of rutin. PMID:19067170

  9. 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

  10. Effect of quercetin on colon contractility and L-type Ca(2+) channels in colon smooth muscle of guinea-pig.

    PubMed

    Huang, Wei-Feng; Ouyang, Shou; Li, Shi-Ying; Lin, Yan-Fei; Ouyang, Hui; Zhang, Hui; Lu, Chun-Jing

    2009-12-25

    The aim of the present study was to investigate the effects of quercetin on colon contractility and voltage-dependent Ca(2+) channels in the single smooth muscle cell isolated from the proximal colon of guinea-pig and to clarify whether its effect on L-type Ca(2+) current (I(Ca,L)) would be related to its myorelaxing properties. Colon smooth muscle strips were used to take contractile tension recordings. Smooth muscle cells were freshly isolated from the proximal colon of guinea-pig by means of papain treatment. I(Ba,L) (barium instead of calcium as current carrier) was measured by using whole-cell patch-clamp techniques. The results showed that quercetin relaxed colon muscle strips in a concentration-dependent manner and antagonized the contractile effect of acetylcholine and neostigmine. Preincubation with indomethcin [cyclooxygenase (COX) inhibitor] and methylene blue [guanylate cyclase (GC) inhibitor] significantly attenuated the relaxing effect of quercetin, respectively. Quercetin increased I(Ba,L) in a concentration- [EC(50)= (7.59+/-0.38) mumol/L] and voltage-dependent pattern, and shifted the maximum of the current-voltage curve by 10 mV in the depolarizing direction without modifying the threshold potential for Ca(2+) influx. Quercetin shifted the steady-state inactivation curve toward more positive potentials by approximately 3.75 mV without affecting the slope of activation and inactivation curve. H-89 (PKA inhibitor) abolished quercetin-induced I(Ba,L) increase, while cAMP enhanced the quercetin-induced I(Ba,L) increase. The patch-clamp results proved that quercetin increased I(Ba,L) via PKA pathway. It is therefore suggested that the relaxing effect of quercetin attributes to the interaction of GC and COX stimulation, as well as the antagonism effect on acetylcholine, which hierarchically prevails over the increase in the Ca(2+) influx to be expected from I(Ca,L) stimulation. PMID:20029691

  11. Quercetin attenuates the development of 7, 12-dimethyl benz (a) anthracene (DMBA) and croton oil-induced skin cancer in mice

    PubMed Central

    Ali, Huma; Dixit, Savita

    2015-01-01

    Abstract To evaluate the chemopreventive potential of quercetin in an experimental skin carcinogenesis mouse model. Skin tumor was induced by topical application of 7, 12-dimethyl Benz (a) anthracene (DMBA) and Croton oil in Swiss albino mouse. Quercetin was orally administered at a concentration of 200 mg/kg and 400 mg/kg body weight daily for 16 weeks in mouse to evaluate chemopreventive potential. Skin cancer was assessed by histopathological analysis. We found that quercetin reduced the tumor size and the cumulative number of papillomas. The mean latent period was significantly increased as compared to carcinogen treated controls. Quercetin significantly decreased the serum levels of glutamate oxalate transaminase, glutamate pyruvate transaminase, alkaline phosphatase and bilirubin. It significantly increased the levels of glutathione, superoxide dismutase and catalase. The elevated level of lipid peroxides in the control group was significantly inhibited by quercetin. Futhermore, DNA damage was significantly decreased in quercetin treated mice as compared to DMBA and croton oil treated mice. The results suggest that quercetin exerts chemopreventive effect on DMBA and croton oil induced skin cancer in mice by increasing antioxidant activities. PMID:25859269

  12. 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

  13. Prevention of N-nitrosodiethylamine-induced lung tumorigenesis by ellagic acid and quercetin in mice.

    PubMed

    Khanduja, K L; Gandhi, R K; Pathania, V; Syal, N

    1999-04-01

    The polyphenolic antioxidants, consumed as an integral part of vegetables, fruits and beverages, are suggested as possessing anticarcinogenic properties. In the present study we have looked into the anticarcinogenic potential of plant polyphenols ellagic acid (EA) and quercetin against N-nitrosodiethylamine-induced lung tumorigenesis in mice. Ellagic acid was able to significantly reduce tumour incidence to 20% from the control value of 72.2%. Similarly, tumour burden was also decreased, although not significantly, from 3.15 to 2.5. Quercetin (QR) caused the tumour incidence to decrease from 76.4% to 44.4% when fed until the third dose of carcinogen. Both of the polyphenols suppressed the tumour incidence mainly by acting at the initiation phase of the carcinogenesis, since continuing the feeding of polyphenols until the termination of the experiment did not cause any apparent change in tumour incidence or tumour burden. Besides this, ellagic acid was found to be a better chemopreventor than quercetin. In order to search for their mechanism of action, the effect of feeding of these compounds on reduced glutathione (GSH), an important endogenous antioxidant, and on lipid peroxidation was investigated. Both ellagic acid and QR caused a significant increase in GSH and decrease in NADPH- and ascorbate-dependent lipid peroxidation. Ellagic acid was found to be more effective in decreasing the lipid peroxidation and increasing the GSH. This may be one of the reasons for its observed better anticarcinogenic property as compared to quercetin. PMID:10418948

  14. Inhibition of the organic anion-transporting polypeptide 1B1 by quercetin: an in vitro and in vivo assessment

    PubMed Central

    Wu, Lan-Xiang; Guo, Cheng-Xian; Chen, Wang-Qing; Yu, Jing; Qu, Qiang; Chen, Yao; Tan, Zhi-Rong; Wang, Guo; Fan, Lan; Li, Qing; Zhang, Wei; Zhou, Hong-Hao

    2012-01-01

    AIM To investigate the effect of quercetin on organic anion transporting polypeptide 1B1 (OATP1B1) activities in vitro and on the pharmacokinetics of pravastatin, a typical substrate for OATP1B1 in healthy Chinese-Han male subjects. METHODS Using human embryonic kidney 293 (HEK293) cells stably expressing OATP1B1, we observed the effect of quercetin on OATP1B1-mediated uptake of estrone-3-sulphate (E3S) and pravastatin. The influence of quercetin on the pharmacokinetics of pravastatin was measured in 16 healthy Chinese-Han male volunteers receiving a single dose of pravastatin (40 mg orally) after co-administration of placebo or 500 mg quercetin capsules (once daily orally for 14 days). RESULTS Quercetin competitively inhibited OATP1B1-mediated E3S uptake with a Ki value of 17.9 ± 4.6 µm and also inhibited OATP1B1-mediated pravastatin uptake in a concentration dependent manner (IC50, 15.9 ± 1.4 µm). In healthy Chinese-Han male subjects, quercetin increased the pravastatin area under the plasma concentration – time curve (AUC(0,10 h) and the peak plasma drug concentration (Cmax) to 24% (95% CI 15, 32%, P < 0.001) and 31% (95% CI 20, 42%, P < 0.001), respectively. After administration of quercetin, the elimination half-life (t1/2) of pravastatin was prolonged by 14% (95% CI 4, 24%, P = 0.027), with no change in the time to reach Cmax (tmax). Moreover, quercetin decreased the apparent clearance (CL/F) of pravastatin by 18% (95% CI 75, 89%, P < 0.001). CONCLUSIONS These findings suggest that quercetin inhibits the OATP1B1-mediated transport of E3S and pravastatin in vitro and also has a modest inhibitory influence on the pharmacokinetics of pravastatin in healthy Chinese-Han male volunteers. The effects of quercetin on other OATP1B1 substrate drugs deserve further investigation. PMID:22114872

  15. The reversibility of the glutathionyl-quercetin adduct spreads oxidized quercetin-induced toxicity

    SciTech Connect

    Boots, Agnes W. . E-mail: a.boots@farmaco.unimaas.nl; Balk, Jiska M.; Bast, Aalt; Haenen, Guido R.M.M.

    2005-12-16

    Quercetin is one of the most prominent dietary antioxidants. During its antioxidant activity, quercetin becomes oxidized into its o-quinone/quinone methide QQ. QQ is toxic since it instantaneously reacts with thiols of, e.g., proteins. In cells, QQ will initially form an adduct with glutathione (GSH), giving GSQ. We have found that GSQ is not stable; it dissociates continuously into GSH and QQ with a half life of 2 min. Surprisingly, GSQ incubated with 2-mercapto-ethanol (MSH), a far less reactive thiol, results in the conversion of GSQ into the MSH-adduct MSQ. A similar conversion of GSQ into relatively stable protein thiol-quercetin adducts is expected. With the dithiol dihydrolipoic acid (L(SH){sub 2}), quercetin is formed out of GSQ. These results indicate that GSQ acts as transport and storage of QQ. In that way, the initially highly focussed toxicity of QQ is dispersed by the formation of GSQ that finally spreads QQ-induced toxicity, probably even over cells.

  16. Characterization of citrate capped gold nanoparticle-quercetin complex: Experimental and quantum chemical approach

    NASA Astrophysics Data System (ADS)

    Pal, Rajat; Panigrahi, Swati; Bhattacharyya, Dhananjay; Chakraborti, Abhay Sankar

    2013-08-01

    Quercetin and several other bioflavonoids possess antioxidant property. These biomolecules can reduce the diabetic complications, but metabolize very easily in the body. Nanoparticle-mediated delivery of a flavonoid may further increase its efficacy. Gold nanoparticle is used by different groups as vehicle for drug delivery, as it is least toxic to human body. Prior to search for the enhanced efficacy, the gold nanoparticle-flavonoid complex should be prepared and well characterized. In this article, we report the interaction of gold nanoparticle with quercetin. The interaction is confirmed by different biophysical techniques, such as Scanning Electron Microscope (SEM), Circular Dichroism (CD), Fourier-Transform InfraRed (FT-IR) spectroscopy and Thermal Gravimetric Analysis (TGA) and cross checked by quantum chemical calculations. These studies indicate that gold clusters are covered by citrate groups, which are hydrogen bonded to the quercetin molecules in the complex. We have also provided evidences how capping is important in stabilizing the gold nanoparticle and further enhances its interaction with other molecules, such as drugs. Our finding also suggests that gold nanoparticle-quercetin complex can pass through the membranes of human red blood cells.

  17. 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

  18. 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

  19. 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

  20. The effect of quercetin on oxidative DNA damage and myelosuppression induced by etoposide in bone marrow cells of rats.

    PubMed

    Papież, Monika A

    2014-01-01

    There is increasing evidence for the existence of an association between the presence of etoposide phenoxyl radicals and the development of treatment-related acute myeloid leukemia (t-AML), which occurs in a few percent of patients treated with this chemotherapeutic agent. The most common side effect caused by etoposide is myelosuppression, which limits the use of this effective drug. The goal of the study was to investigate the influence of antioxidant querectin on myelosuppression and oxidative DNA damage caused by etoposide. The influence of quercetin and/or etoposide on oxidative DNA damage was investigated in LT-12 cell line and bone marrow cells of rats via comet assay. The effect of quercetin on myelosuppression induced by etoposide was invetsigated by cytological analysis of bone marrow smears stained with May-Grünwald-Giemsa stain. Etoposide caused a significant increase in oxidative DNA damage in bone marrow cells and LT-12 cell line in comparison to the appropriate controls. Quercetin significantly reduced the oxidative DNA damage caused by etoposide both in vitro and in vivo. Quercetin also significantly protected against a decrease in the percentage of myeloid precursors and erythroid nucleated cells caused by etoposide administration in comparison to the group treated with etoposide alone. The results of the study indicate that quercetin could be considered a protectively acting compound in bone marrow cells during etoposide therapy. PMID:24644549

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. Quercetin inhibits the growth of human gastric cancer stem cells by inducing mitochondrial-dependent apoptosis through the inhibition of PI3K/Akt signaling.

    PubMed

    Shen, Xinsheng; Si, Yaqing; Wang, Zhao; Wang, Jiachen; Guo, Yongqiang; Zhang, Xiefu

    2016-08-01

    Cancer stem cells (CSCs) have recently been linked to new treatment strategies for gastric cancer due to the critical role which they play as the 'heartbeat' of cancer. In the present study, we explored the effects of quercetin, an anti-inflammatory and antiviral compound, on gastric CSCs (GCSCs). We noted that quercetin exerted pronounced inhibitory effects on GCSC survival. Moreover, quercetin induced cell apoptosis in a mitochondrial-dependent manner, as shown by the reduction in mitochondrial membrane potential, the activation of caspase-3 and -9, and the downregulation of Bcl-2, as well as the upregulation of Bax and cytochrome c (Cyt-c). Additionally, a marked decrease in Akt phosphorylation levels was observed following treatment with quercetin, whereas pre-treatment with fumonisin B1 (FB1, Akt activator) significantly attenuated the inhibitory effects of quercetin on cell growth and its promoting effects on mitochondrial-dependent apoptosis. Notably, FB1 enhanced the expression of Bcl-2, which was inhibited by quercetin, and prevented the decrease in mitochondrial membrane potential induced by quercetin. However, the increase in the levels of caspases, Bax and Cyt-c induced by quercetin was also attenuated by the addition of FB1 to the GCSCs. Therefore, our results demonstrate that quercetin triggers mitochondrial apoptotic-dependent growth inhibition via the blockade of phosphoinositide 3-kinase (PI3K)-Akt signaling in GCSCs, indicating a potential target for the treatment of gastric cancer. PMID:27278820

  7. 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

  8. Quercetin-imprinted polymer for anthocyanin extraction from mangosteen pericarp.

    PubMed

    Piacham, Theeraphon; Isarankura-Na-Ayudhya, Chartchalerm; Prachayasittikul, Virapong

    2015-06-01

    Molecular imprinting is a facilitative technology for the production of artificial receptors possessing great endurance with high specificity toward target molecules of interest. The polymers are commonly applied for separation or analysis of substances of interest. In this study, we prepared molecularly imprinted polymers for the purpose of binding specifically to quercetin and related compounds. Quercetin was used as the template molecule, 4-vinylpyridine (4-VP) as the functional monomer, ethylene glycol dimethacrylate (EDMA) as the cross-linking monomer, azobisisobutyronitrile (AIBN) as the polymerization initiator and ethanol as the porogenic solvent. Such 4-VP-based imprinted polymer was found to bind the template molecule greater than that of the control polymer with an approximate 2 folds higher binding using 20mg of polymer in the optimal solvent, ethanol:water (4:1v/v). Quercetin-imprinted polymer (QIP) was found to bind well against its template; approximately 1mg/g polymer. In addition, QIP was applied to bind anthocyanin from the crude extract of mangosteen pericarp. The binding capacity of quercetin-MIP toward anthocyanin was approximately 0.875mg per gram of polymer. This result indicated that quercetin-MIP showed its specific binding to quercetin and related compound particularly anthocyanin. In conclusion, we have demonstrated the successful preparation and utilization of molecularly imprinted polymer for the specific recognition of quercetin as well as structurally related anthocyanins from the mangosteen pericarp with enhanced and robust performance. PMID:25842116

  9. 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

  10. 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.

  11. 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.

  12. Proatherogenic macrophage activities are targeted by the flavonoid quercetin.

    PubMed

    Lara-Guzman, Oscar J; Tabares-Guevara, Jorge H; Leon-Varela, Yudy M; Álvarez, Rafael M; Roldan, Miguel; Sierra, Jelver A; Londoño-Londoño, Julian A; Ramirez-Pineda, Jose R

    2012-11-01

    Many studies have demonstrated that the flavonoid quercetin protects against cardiovascular disease (CVD) and related risk factors. Atherosclerosis, the underlying cause of CVD, is also attenuated by oral quercetin administration in animal models. Although macrophages are key players during fatty streak formation and plaque progression and aggravation, little is known about the effects of quercetin on atherogenic macrophages. Here, we report that primary bone marrow-derived macrophages internalized less oxidized low-density lipoprotein (oxLDL) and accumulated less intracellular cholesterol in the presence of quercetin. This reduction of foam cell formation correlated with reduced surface expression of the oxLDL receptor CD36. Quercetin also targeted the lipopolysaccharide-dependent, oxLDL-independent pathway of lipid droplet formation in macrophages. In oxLDL-stimulated macrophages, quercetin inhibited reactive oxygen species production and interleukin (IL)-6 secretion. In a system that evaluated cholesterol crystal-induced IL-1β secretion via nucleotide-binding domain and leucine-rich repeat containing protein 3 inflammasome activation, quercetin also exhibited an inhibitory effect. Dyslipidemic apolipoprotein E-deficient mice chronically treated with intraperitoneal quercetin injections had smaller atheromatous lesions, reduced lipid deposition, and less macrophage and T cell inflammatory infiltrate in the aortic roots than vehicle-treated animals. Serum levels of total cholesterol and the lipid peroxidation product malondialdehyde were also reduced in these mice. Our results demonstrate that quercetin interferes with both key proatherogenic activities of macrophages, namely foam cell formation and pro-oxidant/proinflammatory responses, and these effects may explain the atheroprotective properties of this common flavonoid. PMID:22869926

  13. Quercetin as a prophylactic measure against high altitude cerebral edema.

    PubMed

    Patir, Himadri; Sarada, S K S; Singh, Saumya; Mathew, Titto; Singh, Bhagwat; Bansal, Anju

    2012-08-15

    The present study was undertaken to elucidate the intervention of quercetin against high altitude cerebral edema (HACE) using male Sprague Dawley rats as an animal model. This study was also programmed to compare and correlate the effect of both quercetin (flavonoid) and dexamethasone (steroid) against HACE. Six groups of animals were designed for this experiment, (I) normoxia, (II) hypoxia (25,000 ft, 24 h), (III) normoxia+quercetin (50 mg/kg body wt), (IV) normoxia+dexamethasone (4 mg/kg body wt), (V) hypoxia+quercetin (50 mg/kg body wt), (VI) hypoxia+dexamethasone (4 mg/kg body wt). Quercetin at 50 mg/kg body wt, orally 1h prior to hypoxia exposure, was considered as the optimum dose, due to a significant reduction in the level of brain water content and cerebral transvascular leakage (P < 0.001), as compared to control (24 h hypoxia). Dexamethasone was administered at 4 mg/kg body wt, orally, 1h prior to hypoxia exposure. Both drugs (quercetin and dexamethasone) could efficiently reduce the hypoxia-induced hematological changes. Quercetin was observed to be a more potent antioxidative and anti-inflammatory agent. It blocks nuclear factor kappa-beta (NFκB) more significantly (P < 0.05) than the dexamethasone-administered hypoxia-exposed rats. Histopathological findings demonstrate the absence of an edema and inflammation in the brain sections of quercetin-administered hypoxia-exposed rats. The present study reveals quercetin to be a potent drug against HACE, as it efficiently attenuates inflammation as well as cerebral edema formation without any side effects of steroid therapy (dexamethasone). PMID:22743108

  14. [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

  15. A transient increase in eosinophils is associated with prolonged survival in men with metastatic castration-resistant prostate cancer who receive sipuleucel-T.

    PubMed

    McNeel, Douglas G; Gardner, Thomas A; Higano, Celestia S; Kantoff, Philip W; Small, Eric J; Wener, Mark H; Sims, Robert B; DeVries, Todd; Sheikh, Nadeem A; Dreicer, Robert

    2014-10-01

    Sipuleucel-T is an autologous cellular immunotherapy used to treat asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC). Traditional short-term indicators of clinical response commonly used with chemotherapy have not correlated with survival in patients treated with sipuleucel-T. This retrospective study aimed to evaluate laboratory parameters as possible early biomarkers associated with clinical benefit following sipuleucel-T treatment. Patients treated with sipuleucel-T from three randomized, controlled, phase III clinical trials in mCRPC were considered: IMPACT (NCT00065442; n = 512), D9901 (NCT00005947; n = 127), and D9902A (NCT01133704; n = 98). Patients from these trials were included in this study if their samples were analyzed by the central laboratory and if data were available from baseline and ≥ 1 posttreatment time point (n = 377). We found that sipuleucel-T treatment was associated with a transient increase in serum eosinophil count at week 6 that resolved by week 14 in 28% of patients (105 of 377). This eosinophil increase correlated with induced immune response, longer prostate cancer-specific survival [HR, 0.713; 95% confidence interval (CI), 0.525-0.970; P = 0.031], and a trend in overall survival (HR, 0.753; 95% CI, 0.563-1.008; P = 0.057). Median serum globulin protein levels also increased transiently, which was associated with antigen-specific antibody responses; however, this finding did not correlate with longer survival. We conclude that transient increases in eosinophils at week 6 may be a useful, objective, short-term indicator of global immune activation and survival benefit with sipuleucel-T in patients with mCRPC. This observation warrants prospective evaluation in future clinical trials. PMID:25189164

  16. A Transient Increase in Eosinophils is Associated with Prolonged Survival in Men with Metastatic Castration-Resistant Prostate Cancer Who Receive Sipuleucel-T

    PubMed Central

    McNeel, Douglas G.; Gardner, Thomas A.; Higano, Celestia S.; Kantoff, Philip W.; Small, Eric J.; Wener, Mark H.; Sims, Robert B.; DeVries, Todd; Sheikh, Nadeem A.; Dreicer, Robert

    2014-01-01

    Sipuleucel-T is an autologous cellular immunotherapy used to treat asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC). Traditional short-term indicators of clinical response commonly used with chemotherapy have not correlated with survival in patients treated with sipuleucel-T. This retrospective study aimed to evaluate laboratory parameters as possible early biomarkers associated with clinical benefit following sipuleucel-T treatment. Patients treated with sipuleucel-T from 3 randomized, controlled, phase III clinical trials in mCRPC were considered: IMPACT (NCT00065442, n = 512), D9901 (NCT00005947, n = 127), and D9902A (NCT01133704, n = 98). Patients from these trials were included in this study if their samples were analyzed by the central laboratory, and if data were available from baseline and ≥1 post-treatment time point (n = 377). We found that sipuleucel-T treatment was associated with a transient increase in serum eosinophil count at week 6 that resolved by week 14 in 28% of patients (105/377). This eosinophil increase correlated with induced immune response, longer prostate cancer-specific survival (HR = 0.713; 95% confidence interval [CI], 0.525–0.970; P = 0.031) and trend in overall survival (HR = 0.753; 95% CI, 0.563–1.008; P = 0.057). Median serum globulin protein levels also increased transiently, which was associated with antigen-specific antibody responses; however, this did not correlate with longer survival. We conclude that transient increases in eosinophils at week 6 may be a useful, objective, short-term indicator of global immune activation and survival benefit with sipuleucel-T in patients with mCRPC. This observation warrants prospective evaluation in future clinical trials. PMID:25189164

  17. 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. PMID:27008429

  18. Stage-specific quercetin sulfation in the gut of Mythimna separata larvae (Lepidoptera: Noctuidae).

    PubMed

    Aboshi, Takako; Ishida, Masahiro; Matsushita, Kaori; Hirano, Yunosuke; Nishida, Ritsuo; Mori, Naoki

    2014-01-01

    The metabolism of quercetin was investigated in Mythimna separata larvae. Quercetin 4'-O-sulfate was mainly identified in the frass when 6th instar larvae were fed artificial diets containing 1% quercetin. In the case of the 3rd instar larvae, a larger amount of quercetin was detected in the frass. M. separata larvae had different metabolic strategies for quercetin at different developmental stages. PMID:25036481

  19. 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. PMID:25447470

  20. 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

  1. 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

  2. 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

  3. 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

    2016-01-01

    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. PMID:27525872

  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

    2016-01-01

    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

  5. Quercetin ameliorates LPS-induced inflammation in human peripheral blood mononuclear cells by inhibition of the TLR2-NF-κB pathway.

    PubMed

    Zhang, M; Lin, J M; Li, X S; Li, J

    2016-01-01

    Quercetin, a dietary flavonoid abundant in fruits, vegetables, and herbs, presents various pharmacological effects. This study aimed to investigate the anti-inflammatory effect and the underlying mechanism of quercetin in lipopolysaccharide (LPS)-stimulated human peripheral blood mononuclear cells (PBMCs). Cell viability was measured by the Cell Counting Kit-8 assay. The mRNA expression of Toll-like receptor 2 (TLR2) was assessed by quantitative real-time polymerase chain reaction. Inflammatory cytokine secretions and nuclear factor (NF)-kB levels were analyzed by enzyme-linked immunosorbent assay. Our findings showed that quercetin significantly reduced LPS-induced cytotoxicity in human PBMCs. Quercetin suppressed the secretion of tumor necrosis factor-a, interleukin (IL)-1b, and IL-6 in LPS-stimulated human PBMCs. Moreover, quercetin reduced the LPS-induced increase in the expression of TLR2 mRNA and decreased the NF-kB concentration in LPS-stimulated human PBMCs. The data indicates that quercetin plays an important role in LPS-induced inflammation in human PBMCs via suppression of the TLR2-NF-kB pathway. PMID:27421015

  6. 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…

  7. Quercetin solubilisation in bile salts: A comparison with sodium dodecyl sulphate.

    PubMed

    Buchweitz, Maria; Kroon, Paul A; Rich, Gillian T; Wilde, Peter J

    2016-11-15

    To understand the bioaccessibility of the flavonoid quercetin we studied its interaction with bile salt micelles. The environmental sensitivity of quercetin's UV-visible absorption spectrum gave information about quercetin partitioning. Two quercetin absorption peaks gave complementary information: Peak A (240-280nm) on the intermicellar phase and Peak B (340-440nm) on the micellar phase. Thus, by altering pH, we showed that only non-ionised quercetin partitions into micelles. We validated our interpretation by studying quercetin's interaction with SDS micelles. Pyrene fluorescence and the quercetin UV-visible spectra show that the adsorption site for pyrene and quercetin in bile salt micelles is more hydrophobic than that for SDS micelles. Also, both quercetin and pyrene reported a higher critical micelle concentration for bile salts than for SDS. Our method of using a flavonoid as an intrinsic probe, is generally applicable to other lipophilic bioactives, whenever they have observable environmental dependent properties. PMID:27283643

  8. 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.

  9. 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.

  10. Therapeutic role of quercetin on oxidative damage induced by acrylamide in rat brain.

    PubMed

    Zargar, Seema; Siddiqi, Nikhat Jamal; Ansar, Sabah; Alsulaimani, Maha Saleh; El Ansary, Afaf K

    2016-09-01

    Context Quercetin (QE), a bioflavonoid present abundantly in fruits and vegetables, has been reported to possess antioxidant properties. Acrylamide (ACR) is formed in foods during cooking and is known to be neurotoxic. Objective The present study was designed to evaluate the protective effect of QE against neurotoxicity induced by ACR. Materials and methods Four groups of Wistar rats consisting of six rats each: (i) control group; (ii) acrylamide treated group (50 mg/kg body weight as single dose); (iii) quercetin group: rats were treated intraperitoneally (i.p.) with QE (10 mg/kg body weight alone every day for 5 d); (iv) quercetin + acrylamide group: quercetin (10 mg/kg bw) was given i.p. every day for 5 d followed by acrylamide i.p. injection (50 mg/kg bw) on fifth day (single dose). Rats were killed after 48 h. Results Administration of ACR (50 mg/kg bw) in Wistar rats resulted in significant increase of dopamine, interferon-γ and 8-hydroxyguanosine with concomitant decrease of serotonin (p < 0.001) in the rat brain. Treatment of rats with QE intraperitonealy (10 mg/kg body weight) before ACR assault resulted in the diminution of ACR-mediated neurotoxicity as evident from decreased levels of dopamine, interferon-γ (p < 0.001) and 8-hydroxyguanosine with concomitant restoration of serotonin levels (p < 0.001). Discussion and conclusion On the basis of the above results, the present study suggests that quercetin may be a potential therapeutic agent for restoration of oxidative damage to neurons. PMID:26730789

  11. Cross-linked chitosan/liposome hybrid system for the intestinal delivery of quercetin.

    PubMed

    Caddeo, Carla; Díez-Sales, Octavio; Pons, Ramon; Carbone, Claudia; Ennas, Guido; Puglisi, Giovanni; Fadda, Anna Maria; Manconi, Maria

    2016-01-01

    Quercetin is a flavonoid with antioxidant/anti-inflammatory properties, poorly absorbed when administered orally. To increase its bioavailability and optimize its release in the intestine, a hybrid system made of liposomes coated with cross-linked chitosan, named TPP-chitosomes, was developed and characterized by light scattering, transmission electron microscopy, differential scanning calorimetry, X-ray powder diffraction and Turbiscan® technology. The TPP-chitosomes were nanosized (∼180 nm), fairly spherical in shape and unilamellar. The actual coating of the surface of liposomes with the cross-linked chitosan was demonstrated by Small-Angle X-ray Scattering. The release of quercetin in simulated gastric and intestinal pH was investigated, the results showing that the system provided resistance to acidic conditions, and promoted the release in alkaline pH, mimicking the intestinal environment. The proposed hybrid system represents a promising combination of nanovesicles and chitosan for the delivery of quercetin to the intestine in the therapy of oxidative stress/inflammation related disorders. PMID:26397912

  12. 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

  13. 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

  14. In mice the efficiency of immunization with Venezuelan Equine Encephalomyelitis virus TC-83 is transiently increased by dehydroepiandrosterone.

    PubMed

    Negrette, B; Bonilla, E; Valero, N; Giraldoth, D; Medina-Leendertz, S; Añez, F

    2001-12-01

    To determine whether treatment with dehydroepiandrosterone (DHEA) improves the efficiency of immunization against the Venezuelan Equine Encephalomyelitis (VEE) virus, mice were vaccinated with the TC-83 VEE virus. DHEA (10 mg/kg) was administered in a single dose, 4 hours before vaccination. IgM antibody titers were determined at days 7, 14 and 21 post-immunization. Treatment with DHEA increased antibody titers at day 14 after immunization. Mice were challenged with live VEE virus at day 21, and viral titers were plaque assayed in chicken embryo fibroblasts from days 2 to 5 post-infection. After the challenge, viremia decreased on day 2 and brain virus levels were reduced at day 4 in mice treated with DHEA. These results suggest that DHEA treatment could enhance the efficiency of immunization against VEE virus in mice. PMID:11787268

  15. Dietary Quercetin Reduces Chemotherapy-Induced Fatigue in Mice

    PubMed Central

    Mahoney, Sara E.; Davis, J. Mark; Murphy, E. Angela; McClellan, Jamie L.; Pena, Marjory M.

    2014-01-01

    Purpose While fatigue is the most commonly reported symptom of chemotherapy, there are currently no effective treatments for chemotherapy-induced fatigue (CIF). We used a mouse model to examine the benefits of quercetin on CIF as measured by voluntary wheel running activity and sought to determine whether quercetin may be associated with a decrease in inflammation and/or anemia. Methods Mice were assigned to 1 of 4 groups: placebo-vehicle (Plac-PBS), placebo-5-fluorouracil (Plac-5FU), quercetin-vehicle (Quer-PBS), or quercetin-5-fluorouracil (Quer-5FU). All mice were given a daily injection of either 60 mg/kg of 5-FU or phosphate buffered saline (PBS) for 5 days. Quercetin (0.02%) treatment was administered in the food 3 days prior to 5-FU administration and for the duration of the experiment (ie, days −2 to 14). A second group of mice was sacrificed at 5 and 14 days post initial injection for assessment of monocyte chemoattractant protein-1 (MCP-1) and anemia. Results Voluntary wheel running was reduced in both the Plac-5FU and Quer-5FU groups following 5-FU injection (P < .05). However, the Quer-5FU group recovered to baseline levels by approximately day 7, whereas the Plac-5FU group remained suppressed. MCP-1 was significantly elevated at 14 days in Plac-5FU (P < .001), but no changes were seen with Quer-5FU. Treatment with 5-FU resulted in anemia at both 5 days and 14 days; however, quercetin blocked this effect at 14 days (P < .001). Conclusion These results demonstrate the beneficial effect of quercetin on improving recovery of voluntary physical activity following 5-FU treatment, which may be linked to a decrease in inflammation and anemia. PMID:24626097

  16. Increased incidence of gap junctional coupling between spinal motoneurones following transient blockade of NMDA receptors in neonatal rats

    PubMed Central

    Mentis, George Z; Díaz, Eugenia; Moran, Linda B; Navarrete, Roberto

    2002-01-01

    Neonatal rat motoneurones are electrically coupled via gap junctions and the incidence of this coupling declines during postnatal development. The mechanisms involved in this developmental regulation of gap junctional communication are largely unknown. Here we have studied the role of NMDA receptor-mediated glutamatergic synaptic activity in the regulation of motoneurone coupling. Gap junctional coupling was demonstrated by the presence of graded, short latency depolarising potentials following ventral root stimulation, and by the transfer of the low molecular weight tracer Neurobiotin to neighbouring motoneurones. Sites of close apposition between the somata and/or dendrites of the dye-coupled motoneurones were identified as potential sites of gap junctional coupling. Early postnatal blockade of the NMDA subtype of glutamate receptors using the non-competitive antagonist dizocilpine maleate (MK801) arrested the developmental decrease in electrotonic and dye coupling during the first postnatal week. These results suggest that the postnatal increase in glutamatergic synaptic activity associated with the onset of locomotion promote the loss of gap junctional connections between developing motoneurones. PMID:12411521

  17. The transient nature of Bunyamwera orthobunyavirus NSs protein expression: effects of increased stability of NSs protein on virus replication.

    PubMed

    van Knippenberg, Ingeborg; Fragkoudis, Rennos; Elliott, Richard M

    2013-01-01

    The NSs proteins of bunyaviruses are the viral interferon antagonists, counteracting the host's antiviral response to infection. During high-multiplicity infection of cultured mammalian cells with Bunyamwera orthobunyavirus (BUNV), NSs is rapidly degraded after reaching peak levels of expression at 12hpi. Through the use of inhibitors this was shown to be the result of proteasomal degradation. A recombinant virus (rBUN4KR), in which all four lysine residues in NSs were replaced by arginine residues, expresses an NSs protein (NSs4KR) that is resistant to degradation, confirming that degradation is lysine-dependent. However, despite repeated attempts, no direct ubiquitylation of NSs in infected cells could be demonstrated. This suggests that degradation of NSs, although lysine-dependent, may be achieved through an indirect mechanism. Infection of cultured mammalian cells or mice indicated no disadvantage for the virus in having a non-degradable NSs protein: in fact rBUN4KR had a slight growth advantage over wtBUNV in interferon-competent cells, presumably due to the increased and prolonged presence of NSs. In cultured mosquito cells there was no difference in growth between wild-type BUNV and rBUN4KR, but surprisingly NSs4KR was not stabilised compared to the wild-type NSs protein. PMID:23667701

  18. The Transient Nature of Bunyamwera Orthobunyavirus NSs Protein Expression: Effects of Increased Stability of NSs Protein on Virus Replication

    PubMed Central

    van Knippenberg, Ingeborg; Fragkoudis, Rennos; Elliott, Richard M.

    2013-01-01

    The NSs proteins of bunyaviruses are the viral interferon antagonists, counteracting the host's antiviral response to infection. During high-multiplicity infection of cultured mammalian cells with Bunyamwera orthobunyavirus (BUNV), NSs is rapidly degraded after reaching peak levels of expression at 12hpi. Through the use of inhibitors this was shown to be the result of proteasomal degradation. A recombinant virus (rBUN4KR), in which all four lysine residues in NSs were replaced by arginine residues, expresses an NSs protein (NSs4KR) that is resistant to degradation, confirming that degradation is lysine-dependent. However, despite repeated attempts, no direct ubiquitylation of NSs in infected cells could be demonstrated. This suggests that degradation of NSs, although lysine-dependent, may be achieved through an indirect mechanism. Infection of cultured mammalian cells or mice indicated no disadvantage for the virus in having a non-degradable NSs protein: in fact rBUN4KR had a slight growth advantage over wtBUNV in interferon-competent cells, presumably due to the increased and prolonged presence of NSs. In cultured mosquito cells there was no difference in growth between wild-type BUNV and rBUN4KR, but surprisingly NSs4KR was not stabilised compared to the wild-type NSs protein. PMID:23667701

  19. 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

  20. Transient Co-Expression of Post-Transcriptional Gene Silencing Suppressors for Increased in Planta Expression of a Recombinant Anthrax Receptor Fusion Protein

    PubMed Central

    Arzola, Lucas; Chen, Junxing; Rattanaporn, Kittipong; Maclean, James M.; McDonald, Karen A.

    2011-01-01

    Potential epidemics of infectious diseases and the constant threat of bioterrorism demand rapid, scalable, and cost-efficient manufacturing of therapeutic proteins. Molecular farming of tobacco plants provides an alternative for the recombinant production of therapeutics. We have developed a transient production platform that uses Agrobacterium infiltration of Nicotiana benthamiana plants to express a novel anthrax receptor decoy protein (immunoadhesin), CMG2-Fc. This chimeric fusion protein, designed to protect against the deadly anthrax toxins, is composed of the von Willebrand factor A (VWA) domain of human capillary morphogenesis 2 (CMG2), an effective anthrax toxin receptor, and the Fc region of human immunoglobulin G (IgG). We evaluated, in N. benthamiana intact plants and detached leaves, the expression of CMG2-Fc under the control of the constitutive CaMV 35S promoter, and the co-expression of CMG2-Fc with nine different viral suppressors of post-transcriptional gene silencing (PTGS): p1, p10, p19, p21, p24, p25, p38, 2b, and HCPro. Overall, transient CMG2-Fc expression was higher on intact plants than detached leaves. Maximum expression was observed with p1 co-expression at 3.5 days post-infiltration (DPI), with a level of 0.56 g CMG2-Fc per kg of leaf fresh weight and 1.5% of the total soluble protein, a ten-fold increase in expression when compared to absence of suppression. Co-expression with the p25 PTGS suppressor also significantly increased the CMG2-Fc expression level after just 3.5 DPI. PMID:21954339

  1. 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

  2. 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

  3. 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

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

    PubMed Central

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

    2015-01-01

    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 Ca2+ 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 Ca2+ handling, isolated cardiomyocytes were loaded with fluo-4. Q510E-SHP2 expression increased Ca2+ transient amplitudes during excitation-contraction coupling and increased sarcoplasmic reticulum Ca2+ content concurrent with increased expression of sarco(endo)plasmic reticulum Ca2+-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 Ca2+ cycling and increasing the number of power-generating sarcomeres. This gives important new insights into the cellular pathomechanisms of Q510E-SHP2-associated HCM. PMID:25724491

  5. 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. PMID:26541297

  6. 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

  7. Quercetin mitigates fenitrothion-induced testicular toxicity in rats.

    PubMed

    Saber, T M; Abd El-Aziz, R M; Ali, H A

    2016-06-01

    Fenitrothion (FNT) is a widely used organophosphorus pesticide in agriculture. Quercetin (QR), a plant-derived flavonoid, has a free radical scavenging property. This study investigated the protective effect of QR on FNT-induced testicular toxicity in rats. Twenty-four male rats were divided into four groups. Group I (control) received normal saline. Group II was administered QR at the dose of 50 mg kg(-1) b.wt. Group III was orally administered FNT (20 mg kg(-1) b.wt). Group IV was gavaged FNT and QR together at the same doses. All administrations were performed daily by gavage and maintained for 70 days. Sperm parameters and histopathological changes in testes were investigated. Serum testosterone and luteinising hormone were estimated using radioimmunoassay kits. In testes, expressions of steroidogenic genes (3β-hydroxysteroid dehydrogenase type 6, 17 β-hydroxysteroid dehydrogenase type 3 and steroidogenic factor-1) and oxidative stress genes (catalase and superoxide dismutase) were determined using real-time PCR. FNT administration caused significant decreases in sperm count, motility and hormonal levels, a significant increase in abnormal sperm morphology and a significant down-regulation of steroidogenic and antioxidant genes in the testis. However, QR administration ameliorated FNT-induced toxic effects. Our results concluded that QR effectively mitigated testicular damage induced by FNT in rats. PMID:26264430

  8. 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

  9. 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

  10. 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