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Sample records for quercetin quercetin-gene interaction

  1. 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

  2. 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

  3. 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

  4. Clinically relevant interaction between warfarin and scuppernongs, a quercetin containing muscadine grape: continued questions surrounding flavonoid-induced warfarin interactions

    PubMed Central

    Woodward, Christopher J; Deyo, Zachariah M; Donahue, Katrina E; Deal, Allison M; Hawes, Emily M

    2014-01-01

    We present a case of clinically relevant and probable interaction between warfarin and scuppernongs in a 73-year-old woman where ingestion of scuppernongs, a variety of quercetin-containing muscadine grapes, over a period of 2 months was associated with elevations in the International Normalised Ratio to supratherapeutic levels. While muscadine grapes and specifically scuppernongs are found primarily in Southeastern USA, the flavonoid in questionand quercetin is found worldwide as a dietary supplement. PMID:24966255

  5. 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

  6. Quercetin targets the interaction of calcineurin with LxVP-type motifs in immunosuppression.

    PubMed

    Zhao, Yane; Zhang, Jin; Shi, Xiaoyu; Li, Jing; Wang, Rui; Song, Ruiwen; Wei, Qun; Cai, Huaibin; Luo, Jing

    2016-08-01

    Calcineurin (CN) is a unique calcium/calmodulin (CaM)-activated serine/threonine phosphatase. To perform its diverse biological functions, CN communicates with many substrates and other proteins. In the physiological activation of T cells, CN acts through transcriptional factors belonging to the NFAT family and other transcriptional effectors. The classic immunosuppressive drug cyclosporin A (CsA) can bind to cyclophilin (CyP) and compete with CN for the NFAT LxVP motif. CsA has debilitating side effects, including nephrotoxicity, hypertension and tremor. It is desirable to develop alternative immunosuppressive agents. To this end, we first tested the interactions between CN and the LxVP-type substrates, including endogenous regulators of calcineurin (RCAN1) and NFAT. Interestingly, we found that quercetin, the primary dietary flavonol, can inhibit the activity of CN and significantly disrupt the associations between CN and its LxVP-type substrates. We then validated the inhibitory effects of quercetin on the CN-NFAT interactions in cell-based assays. Further, quercetin also shows dose-dependent suppression of cytokine gene expression in mouse spleen cells. These data raise the possibility that the interactions of CN with its LxVP-type substrates are potential targets for immunosuppressive agents. PMID:27109380

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

    PubMed Central

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

    1993-01-01

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

  8. Spectrometric and voltammetric studies of the interaction between quercetin and bovine serum albumin using warfarin as site marker with the aid of chemometrics

    NASA Astrophysics Data System (ADS)

    Ni, Yongnian; Zhang, Xia; Kokot, Serge

    2009-01-01

    The interaction of quercetin, which is a bioflavonoid, with bovine serum albumin (BSA) was investigated under pseudo-physiological conditions by the application of UV-vis spectrometry, spectrofluorimetry and cyclic voltammetry (CV). These studies indicated a cooperative interaction between the quercetin-BSA complex and warfarin, which produced a ternary complex, quercetin-BSA-warfarin. It was found that both quercetin and warfarin were located in site I. However, the spectra of these three components overlapped and the chemometrics method - multivariate curve resolution-alternating least squares (MCR-ALS) was applied to resolve the spectra. The resolved spectra of quercetin-BSA and warfarin agreed well with their measured spectra, and importantly, the spectrum of the quercetin-BSA-warfarin complex was extracted. These results allowed the rationalization of the behaviour of the overlapping spectra. At lower concentrations ([warfarin] < 1 × 10 -5 mol L -1), most of the site marker reacted with the quercetin-BSA, but free warfarin was present at higher concentrations. Interestingly, the ratio between quercetin-BSA and warfarin was found to be 1:2, suggesting a quercetin-BSA-(warfarin) 2 complex, and the estimated equilibrium constant was 1.4 × 10 11 M -2. The results suggest that at low concentrations, warfarin binds at the high-affinity sites (HAS), while low-affinity binding sites (LAS) are occupied at higher concentrations.

  9. Quercetin inhibits the 5-hydroxytryptamine type 3 receptor-mediated ion current by interacting with pre-transmembrane domain I.

    PubMed

    Lee, Byung-Hwan; Jeong, Sang-Min; Jung, Sang-Min; Lee, Jun-Ho; Kim, Jong-Hoon; Yoon, In-Soo; Lee, Joon-Hee; Choi, Sun-Hye; Lee, Sang-Mok; Chang, Choon-Gon; Kim, Hyung-Chun; Han, YeSun; Paik, Hyun-Dong; Kim, Yangmee; Nah, Seung-Yeol

    2005-08-31

    The flavonoid, quercetin, is a low molecular weight substance found in apple, tomato and other fruit. Besides its antioxidative effect, quercetin, like other flavonoids, has a wide range of neuropharmacological actions including analgesia, and motility, sleep, anticonvulsant, sedative and anxiolytic effects. In the present study, we investigated its effect on mouse 5-hydroxytryptamine type 3 (5-HT3A) receptor channel activity, which is involved in pain transmission, analgesia, vomiting, and mood disorders. The 5-HT3A receptor was expressed in Xenopus oocytes, and the current was measured with the two-electrode voltage clamp technique. In oocytes injected with 5-HT3A receptor cRNA, quercetin inhibited the 5-HT-induced inward peak current (I(5-HT)) with an IC50 of 64.7 +/- 2.2 microM. Inhibition was competitive and voltage-independent. Point mutations of pre-transmembrane domain 1 (pre-TM1) such as R222T and R222A, but not R222D, R222E and R222K, abolished inhibition, indicating that quercetin interacts with the pre-TM1 of the 5-HT3A receptor. PMID:16258243

  10. Fluorescence quenching study of quercetin interaction with bovine milk xanthine oxidase

    NASA Astrophysics Data System (ADS)

    Rasoulzadeh, Farzaneh; Jabary, Hamideh Nadjarpour; Naseri, Abdolhossein; Rashidi, Mohammad-Reza

    2009-02-01

    Quercetin is a natural flavonoid with many important therapeutic properties. The interaction of this polyphenolic compound bovine milk xanthine oxidase as one of its major target proteins was studied using fluorescence quenching method for the first time. It was found that the fluorescence quenching of xanthine oxidase occurs through a static mechanism. The results revealed the presence of a single binding site on xanthine oxidase with the binding constant value equals to 1.153 × 10 4 l mol -1 at 310 K and pH 7.4. The thermodynamic parameters were also calculated at different temperatures. The enthalpy and entropy changes were found as -10.661 kJ mol -1 and +43.321 J mol -1 K -1 indicating that both hydrogen binding and hydrophobic are involved in the interaction of this polyphenolic natural compound with xanthine oxidase. The results may provide a ground for further studies with different flavonoids to find a safe alternative for allopurinol, the only xanthine oxidase inhibitor with clinical application.

  11. Lipid-based nanocarrier for quercetin delivery: system characterization and molecular interactions studies.

    PubMed

    Hädrich, Gabriela; Monteiro, Samantha Oliveira; Rodrigues, Marisa Raquel; de Lima, Vânia Rodrigues; Putaux, Jean-Luc; Bidone, Juliana; Teixeira, Helder Ferreira; Muccillo-Baisch, Ana Luiza; Dora, Cristiana Lima

    2016-07-01

    The flavonoid quercetin (QU) is a naturally occurring compound with several biological activities. However, the oral bioavailability of this compound is very low due to the high pre-systemic metabolism in the colon and liver and its low water solubility. In this context, the development of QU-loaded nanocarriers (NEs) is a promising approach to improve the drug oral bioavailability. This study investigates the variation of the concentration of 12-hydroxystearic acid-polyethylene glycol copolymer, lecithin and castor oil (CO) as to increase the amount of QU encapsulated while maintaining physicochemical characteristics described in previous studies. To better understand the ability to load and release the drug, we investigated the molecular interactions between QU and NE. Lipid-based NEs were prepared using CO as oily phase and PEG 660-stearate and lecithin as surfactants. Hot solvent diffusion and phase inversion temperature were methods employed to produce NEs. The QU-NEs were investigated for physicochemical characteristics and in vitro drug release. Molecular interactions between QU and the NEs were monitored through the complementary infrared (Fourier transform infrared) and NMR. The results revealed that it was possible to incorporate higher amounts of QU in a lipid-based NE with a reduced size (20 nm). The system developed allow a sustained release of QU probably due to the shell formed by the surfactants around the NE and the flavonoid ordering effect in the emulsion hydrophobic regions, which may reduce the system permeability. PMID:26571009

  12. Mapping the interactions and bioactivity of quercetin-(2-hydroxypropyl)-β-cyclodextrin complex.

    PubMed

    Kellici, Tahsin F; Chatziathanasiadou, Maria V; Diamantis, Dimitris; Chatzikonstantinou, Alexandra V; Andreadelis, Ioannis; Christodoulou, Eirini; Valsami, Georgia; Mavromoustakos, Thomas; Tzakos, Andreas G

    2016-09-10

    Natural products have served as a rich source for drug discovery and development. In the last decade their fruitful integration in the drug discovery pipeline declined due to their reduced bioavailability, mainly attributed to their poor aqueous solubility. We synthesized a quercetin (QUE)-(2-hydroxypropyl)-β-cyclodextrin (HP-β-CD) complex that enabled amplification of its solubility and in the same time retained its bioactivity in T24 human bladder cancer cell line. The stability of the complex and the molecular basis of the interactions developed in this host-guest complex were assayed by incorporating an array of analytical techniques and Molecular Dynamics (MD) experiments. 2D DOSY NMR experiment revealed that the diffusion coefficient of free HP-β-CD was 3.55×10(-10)m(2)s(-1) while that of QUE-HP-β-CD inclusion complex 3.09×10(-10)m(2)s(-1), indicating the formation of a complex. Solid and liquid high resolution NMR spectroscopy data showed that the most pronounced differences in chemical shifts at carbons and protons correspondingly during complexation occur in the aromatic ring Α (bearing the two phenolic hydroxyl groups meta to each other). The chemical shift differences in the aromatic ring Β (bearing the two phenolic hydroxyl groups ortho to each other) were less pronounced. The MD results confirmed the experimental data. PMID:27395802

  13. Investigation of the interaction between quercetin and human serum albumin by multiple spectra, electrochemical impedance spectra and molecular modeling.

    PubMed

    Dai, Jie; Zou, Ting; Wang, Li; Zhang, Yezhong; Liu, Yi

    2014-12-01

    Quercetin (Qu), a flavonoid compound, exists widely in the human diet and exhibits a variety of pharmacological activities. This work is aimed at studying the effect of Qu on the bioactive protein, human serum albumin (HSA) under simulated biophysical conditions. Multiple spectroscopic methods (including fluorescence and circular dichroism), electrochemical impedance spectra (EIS) and molecular modeling were employed to investigate the interaction between Qu and HSA. The fluorescence quenching and EIS experimental results showed that the fluorescence quenching of HSA was caused by formation of a Qu-HSA complex in the ground state, which belonged to the static quenching mechanism. Based on the calculated thermodynamic parameters, it concluded that the interaction was a spontaneous process and hydrogen bonds combined with van der Waal's forces played a major role in stabilizing the Qu-HSA complex. Molecular modeling results demonstrated that several amino acids participated in the binding process and the formed Qu-HSA complex was stabilized by H-bonding network at site I in sub-domain IIA, which was further confirmed by the site marker competitive experiments. The evidence from circular dichroism (CD) indicated that the secondary structure and microenvironment of HSA were changed. Alterations in the conformation of HSA were observed with a reduction in the amount of α helix from 59.9% (free HSA) to 56% (Qu-HSA complex), indicating a slight unfolding of the protein polypeptides. PMID:24801949

  14. Synergistic interactions of apigenin, naringin, quercetin and emodin on inhibition of 3T3-L1 preadipocyte differentiation and pancreas lipase activity.

    PubMed

    Guo, XiaoXuan; Liu, Jia; Cai, ShengBao; Wang, Ou; Ji, BaoPing

    2016-01-01

    The interactions of four natural compounds including apigenin, naringin, emodin and quercetin were investigated on inhibiting 3T3-L1 preadipocyte differentiation and pancreas lipase activity. Oil Red O staining was conducted to visualise and quantify lipid accumulation. The difference between experimental and calculated results was utilised for determining the interaction types. Interestingly, emodin synergistically interacted with the other three compounds, and the combination of emodin and apigenin exhibited the strongest synergistic effect in both differentiation and pancreas lipase assays. Results implied that the combination of apigenin and emodin may be regarded as a promising complementary therapy for management of overweight or obesity. PMID:26314502

  15. 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

  16. 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

  17. 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

  18. 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.

  19. 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

  20. 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.

  1. Inhibitory effect of quercetin in the formation of advance glycation end products of human serum albumin: An in vitro and molecular interaction study.

    PubMed

    Alam, Md Maroof; Ahmad, Irshad; Naseem, Imrana

    2015-08-01

    Non-enzymatic glycation entails the reaction between the carbonyl group of a sugar with the amino group of a protein giving rise to Schiff base and Amadori products. The formation of advanced glycation end products (AGEs) leads to the generation of free radicals, which play an important role in the pathophysiology of ageing and diabetes. Bioavailable dietary antioxidants like quercetin (QC) are thought to inhibit AGEs formation. This study was aimed to investigate the effect of quercetin on AGE formation and features the glycation of human serum albumin (HSA) and its characterization by various spectroscopic techniques. The effect of quercetin, against the formation of AGEs was studied using a glycated human serum albumin product, haemoglobin-δ-gluconolactone, and aminoguanidine. The results were then corroborated with estimation of protein oxidation, lipid peroxidation and comet assay. On the basis of the experimental data, computational docking studies were then performed to understand the location of the site of quercetin binding and its best bound conformation with respect to human serum albumin. Through this study we have demonstrated the mechanism of formation of AGE and its inhibition by quercetin. We have also suggested that the supplementation with dietary antioxidants like quercetin might protect against free radical toxicity. PMID:25982953

  2. Raman and surface-enhanced Raman scattering (SERS) investigation of the quercetin interaction with metals: Evidence of structural changing processes in aqueous solution and on metal nanoparticles

    NASA Astrophysics Data System (ADS)

    Jurasekova, Z.; Torreggiani, A.; Tamba, M.; Sanchez-Cortes, S.; Garcia-Ramos, J. V.

    2009-01-01

    The structural modifications of quercetin (QUC), one of the most common dietary flavonols also used as dye, were investigated in this work at alkaline pH and in the presence of metal ions. The parallel analysis of the Raman and surface-enhanced Raman scattering (SERS) and the UV-vis spectra allowed to demonstrate that the interaction of QUC with Zn(II), Cu(II), or Ag(I) ions can result in the formation of complexes and/or the oxidation of the molecule. The catechol group in the B-ring resulted to be important both for metal chelation and in oxidation processes. In fact, the conversion of this reactive group to o-quinone is the first step of the QUC oxidizing processes which are strongly affected by pH both in the absence and in the presence of metal ions. In alkaline solutions (pH > 9.5) the autoxidation processes of QUC initially lead to the formation of a benzofuranone derivative and, successively, to oligomeric/polymeric species. The QUC oxidation takes place also at lower pH in the presence of metal ions such as silver. In this case, QUC acts only as a reductant and not as a metal-chelating agent. The existence of several condensation pathways was clearly evidenced by the SERS spectra. In fact, depending on pH the interaction of QUC with metal nanoparticles favors one or more polymerization reactions. In particular, the "head to tail" condensations (A-ring of one unit and the B-ring of another) seem to be favored under alkaline conditions.

  3. 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

  4. Structure-spectrophotometric selectivity relationship in interactions of quercetin related flavonoids with double stranded and single stranded RNA

    NASA Astrophysics Data System (ADS)

    Piantanida, Ivo; Mašić, Lozika; Rusak, Gordana

    2009-04-01

    Interactions of five flavonoids with dsRNA and single stranded ssRNA were studied by UV/vis titrations. The results obtained supported the intercalative binding mode as a dominant interaction of studied flavonoids with dsRNA as well as major interaction with ssRNA. Furthermore, changes of the UV/vis spectra of flavonoids induced by addition of poly G or poly C, respectively, are significantly stronger than changes induced by double stranded poly G-poly C, pointing to essential role of the free poly G or poly C sequence (not hydrogen bonded in double helix). Exclusively poly G caused significant batochromic shift of the UV/vis maxima of all studied flavonoids, whereby the intensity of batochromic shift is nicely correlated to the number of OH groups of flavonoid. Unlikely to poly G, addition of poly A and poly U induced measurable changes only in the UV/vis spectra of flavonoids characterised by no OH (galangin) or three OH groups (myricetin) on the phenyl part of the molecule. Consequently, flavonoids with one- or two-OH groups on the phenyl part of the molecule (luteolin, fisetin, kaempferol) specifically differentiate between poly A, poly U (negligible changes in the UV/Vis spectra) and poly G (strong changes in the UV/Vis spectra) as well as poly C (moderate changes in the UV/Vis spectra).

  5. Decavanadate, decaniobate, tungstate and molybdate interactions with sarcoplasmic reticulum Ca(2+)-ATPase: quercetin prevents cysteine oxidation by vanadate but does not reverse ATPase inhibition.

    PubMed

    Fraqueza, Gil; Batista de Carvalho, Luís A E; Marques, M Paula M; Maia, Luisa; Ohlin, C André; Casey, William H; Aureliano, Manuel

    2012-11-01

    Recently we demonstrated that the decavanadate (V(10)) ion is a stronger Ca(2+)-ATPase inhibitor than other oxometalates, such as the isoelectronic and isostructural decaniobate ion, and the tungstate and molybdate monomer ions, and that it binds to this protein with a 1 : 1 stoichiometry. The V(10) interaction is not affected by any of the protein conformations that occur during the process of calcium translocation (i.e. E1, E1P, E2 and E2P) (Fraqueza et al., J. Inorg. Biochem., 2012). In the present study, we further explore this subject, and we can now show that the decaniobate ion, [Nb(10) = Nb(10)O(28)](6-), is a useful tool in deducing the interaction and the non-competitive Ca(2+)-ATPase inhibition by the decavanadate ion [V(10) = V(10)O(28)](6-). Moreover, decavanadate and vanadate induce protein cysteine oxidation whereas no effects were detected for the decaniobate, tungstate or molybdate ions. The presence of the antioxidant quercetin prevents cysteine oxidation, but not ATPase inhibition, by vanadate or decavanadate. Definitive V(IV) EPR spectra were observed for decavanadate in the presence of sarcoplasmic reticulum Ca(2+)-ATPase, indicating a vanadate reduction at some stage of the protein interaction. Raman spectroscopy clearly shows that the protein conformation changes that are induced by V(10), Nb(10) and vanadate are different from the ones induced by molybdate and tungstate monomer ions. Here, Mo and W cause changes similar to those by phosphate, yielding changes similar to the E1P protein conformation. The putative reduction of vanadium(V) to vanadium(IV) and the non-competitive binding of the V(10) and Nb(10) decametalates may explain the differences in the Raman spectra compared to those seen in the presence of molybdate or tungstate. Putting it all together, we suggest that the ability of V(10) to inhibit the Ca(2+)-ATPase may be at least in part due to the process of vanadate reduction and associated protein cysteine oxidation. These

  6. Quercetin suppresses insulin receptor signaling through inhibition of the insulin ligand–receptor binding and therefore impairs cancer cell proliferation

    SciTech Connect

    Wang, Feng; Yang, Yong

    2014-10-03

    Graphical abstract: - Highlights: • Quercetin inhibits insulin ligand–receptor interactions. • Quercetin reduces downstream insulin receptor signaling. • Quercetin blocks insulin induced glucose uptake. • Quercetin suppresses insulin stimulated cancer cell proliferation and tumor growth. - Abstract: Although the flavonoid quercetin is known to inhibit activation of insulin receptor signaling, the inhibitory mechanism is largely unknown. In this study, we demonstrate that quercetin suppresses insulin induced dimerization of the insulin receptor (IR) through interfering with ligand–receptor interactions, which reduces the phosphorylation of IR and Akt. This inhibitory effect further inhibits insulin stimulated glucose uptake due to decreased cell membrane translocation of glucose transporter 4 (GLUT4), resulting in impaired cancer cell proliferation. The effect of quercetin in inhibiting tumor growth was also evident in an in vivo model, indicating a potential future application for quercetin in the treatment of cancers.

  7. 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

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

    PubMed

    Zahorodnyĭ, M I

    2007-01-01

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

  9. Quercetin represses apolipoprotein B expression by inhibiting the transcriptional activity of C/EBPβ.

    PubMed

    Shimizu, Makoto; Li, Juan; Inoue, Jun; Sato, Ryuichiro

    2015-01-01

    Quercetin is one of the most abundant polyphenolic flavonoids found in fruits and vegetables and has anti-oxidative and anti-obesity effects. Because the small intestine is a major absorptive organ of dietary nutrients, it is likely that highly concentrated food constituents, including polyphenols, are present in the small intestinal epithelial cells, suggesting that food factors may have a profound effect in this tissue. To identify novel targets of quercetin in the intestinal enterocytes, mRNA profiling using human intestinal epithelial Caco-2 cells was performed. We found that mRNA levels of some apolipoproteins, particularly apolipoprotein B (apoB), are downregulated in the presence of quercetin. On the exposure of Caco-2 cells to quercetin, both mRNA and protein levels of apoB were decreased. Promoter analysis of the human apoB revealed that quercetin response element is localized at the 5'-proximal promoter region, which contains a conserved CCAAT enhancer-binding protein (C/EBP)-response element. We found that quercetin reduces the promoter activity of apoB, driven by the enforced expression of C/EBPβ. Quercetin had no effect on either mRNA or protein levels of C/EBPβ. In contrast, we found that quercetin inhibits the transcriptional activity of C/EBPβ but not its recruitment to the apoB promoter. On the exposure of Caco-2 cells to quercetin 3-O-glucuronide, which is in a cell-impermeable form, no notable change in apoB mRNA was observed, suggesting an intracellular action of quercetin. In vitro interaction experiments using quercetin-conjugated beads revealed that quercetin binds to C/EBPβ. Our results describe a novel regulatory mechanism of transcription of apolipoprotein genes by quercetin in the intestinal enterocytes. PMID:25875015

  10. 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

  11. 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

  12. 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

  13. Effects of dietary quercetin on performance and cytochrome P450 expression of the cotton bollworm, Helicoverpa armigera.

    PubMed

    Liu, D; Yuan, Y; Li, M; Qiu, X

    2015-12-01

    Quercetin is ubiquitous in terrestrial plants. The cotton bollworm Helicoverpa armigera as a highly polyphagous insect has caused severe crop losses. Until now, interactions between this pest and quercetin are poorly understood at the biochemical and molecular levels. In this study, we investigated the in vivo effects of quercetin on performance of cotton bollworm and on cytochrome P450 (P450) expression. Deleterious effects of quercetin on the performance of the cotton bollworm, including growth, survival, pupation and adult emergence were observed after oral administration of 3 and 10 mg g(-1) quercetin to larvae since the third instar, whereas no significant toxic effect was found at 0.1 mg g(-1) quercetin treatment. Piperonyl butoxide treatment enhanced the toxicity of quercetin. In vitro metabolism studies showed that quercetin was rapidly transformed by gut enzymes of fifth instar larvae of the cotton bollworm. qRT-PCR results revealed that the effect of quercetin on P450 expression was tissue- and dose-specific. Quercetin regulated P450 expression in a mild manner, and it could serve as P450 inducer (CYP337B1, CYP6B6) or repressor (CYP337B1, CYP6B7, CYP6B27, CYP9A14, CYP6AE11, and CYP4M7). These findings are important for advancing our understanding of the biochemical and molecular response of insects to plant toxins and have implications for a smart pest control. PMID:26440448

  14. 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

  15. Quercetin negatively regulates TLR4 signaling induced by lipopolysaccharide through Tollip expression.

    PubMed

    Byun, Eui-Baek; Yang, Mi-So; Choi, Han-Gyu; Sung, Nak-Yun; Song, Du-Sup; Sin, Sung-Jae; Byun, Eui-Hong

    2013-02-22

    Polyphenolic compounds have been regarded as one of the most promising dietary agents for the prevention and treatment of inflammation-related chronic diseases; however, the anti-inflammatory activities of flavonoids, such as quercetin, are not completely characterized, and many features remain to be elucidated. In this study, we showed the molecular basis for the downregulation of TLR4 signal transduction by quercetin. Quercetin markedly elevated the expression of the Toll-interacting protein, a negative regulator of TLR signaling. Lipopolysaccharide-induced expression of cell surface molecules (CD80, CD86, and MHC class I/II) and production of pro-inflammatory cytokines (tumor necrosis factor-α, IL-1β, IL-6, and IL-12p70) were inhibited by quercetin, and this action was prevented by Toll-interacting protein silencing. In addition, quercetin-treated macrophages inhibited lipopolysaccharide-induced activation of mitogen-activated protein kinases, such as extracellular signal-regulated kinase 1/2, p38, and c-Jun N-terminal kinase, and the translocation of nuclear factor-κB and p65 through Toll-interacting protein. Treatment with quercetin resulted in a significant decrease in prostaglandin E2 and cyclooxygenase-2 levels as well as inducible nitric oxide synthase-mediated nitric oxide production induced by lipopolysaccharide. Taken together, these findings represent new insights into the understanding of negative regulatory mechanisms of the TLR4 signaling pathway and effective therapeutic intervention for the treatment of inflammatory disease. PMID:23353651

  16. 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

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

    PubMed

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

    2015-07-01

    Quercetin and quercetin glucosides are the major flavonols present in onion (Allium cepa L.) and are predominantly present as quercetin, quercetin-3,4'-diglucoside and quercetin-4'-glucoside. Effect of different light wavelengths on onion after harvest and storage, with fluorescent, blue, red and ultra violet light influenced the quercetin and quercetin glucosides profile. In a peeled onion, all the light treatments elevated quercetin content in bulb. Among them, particularly fluorescent light effect was more eminent which stimulates the maximum synthesis of quercetin in onion. In case of whole onion bulb, skin and pulp showed different responses to light treatment, respectively. The pulp had the highest quercetin glucosides under blue light, whereas the lowest under fluorescent light. Onion skin showed nearly opposite pattern as compared to the pulp. In particular, light treatment proved to be a better way to increase the level of quercetin content in onions which might be utilized for industrial production of bioactive compounds from onion and onion waste products. PMID:26150744

  18. 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

  19. 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

  20. 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

  1. Synthesis, characterization and antioxidant activity copper-quercetin complex

    NASA Astrophysics Data System (ADS)

    Bukhari, S. Birjees; Memon, Shahabuddin; Mahroof-Tahir, M.; Bhanger, M. I.

    2009-01-01

    Quercetin (3,3',4',5,7-pentahydroxyflavone) one of the most abundant dietary flavonoids, has been investigated in the presence of Cu(II) in methanol. The spectroscopic studies (UV-vis, 1H NMR and IR) were useful to assess the relevant interaction of Quercetin with Cu(II) ions, the chelation sites and dependence of the complex structure from the metal/ligand ratio. A 1:2 (L:M) complex was indicated by Job's method of continuous variation, which was applied to ascertain the stoichiometric composition of the complex. The antioxidant activities of the compounds were evaluated by using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging method. The complexed flavonoid was much more effective free radical scavengers than the free flavonoids.

  2. 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

  3. Quercetin-induced apoptosis prevents EBV infection

    PubMed Central

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

    2015-01-01

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

  4. Role of quercetin on mitomycin C induced genotoxicity: analysis of micronucleus and chromosome aberrations in vivo.

    PubMed

    Mazumdar, Mehnaz; Giri, Sarbani; Giri, Anirudha

    2011-04-01

    Quercetin, a flavonol group of plant flavonoid, has generated immense interest because of its potential antioxidant, anti-proliferative, chemoprotective, anti-inflammatory and gene expression modulating properties. However, the pro-oxidant chemistry of quercetin is important as it is related to the generation of mutagenic quinone-type metabolites. In the present study, 25mg/kg, 50mg/kg and 100mg/kg of quercetin given through the intra peritoneal (i.p.) route induced 2.31 ± 0.27%, 4.72 ± 0.58% and 6.38 ± 0.68% (control value=0.67 ± 0.30%) respectively, of cells with micronucleus (MN) in polychromatic erythrocytes in bone marrow cells and 10.93 ± 0.98%, 10.00 ± 0.89% and 14.27 ± 3.94% (control 2.61 ± 0.48) of cells with chromosome aberrations (CA) following 24h of the treatments. Higher frequencies of MN and CA were also observed after 48h of the treatments. To verify the effect of route of treatment on the quercetin induced damage, 100mg/kg b.w. was given through oral route which declined frequency of MN (P<0.001) as well as CA (P<0.05) as compared to the i.p. route for the same dose. Quercetin also induced higher frequency of metaphases with sticky chromosomes and C-mitosis. Pre-treatment with quercetin significantly reduced the frequency of mitomycin C (MMC) induced MN as well as CA, but no clear correlation between the dose and effect could be observed. Further studies are required to elucidate the possible interaction of quercetin with DNA as well as with other DNA damaging agents like MMC in vivo. The protective action of quercetin was not enhanced when given orally. Our findings suggest that quercetin may result in genomic instability in the tested dose range and significant reduction in MMC induced genotoxicity in the highest dose tested. These effects of quercetin are to be taken into consideration while evaluating the possible use of quercetin as a therapeutic agent. PMID:21256974

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

    PubMed

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

    2015-01-01

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

  6. In silico analysis and molecular docking studies of potential angiotensin-converting enzyme inhibitor using quercetin glycosides

    PubMed Central

    Muhammad, Syed Aun; Fatima, Nighat

    2015-01-01

    The purpose of this study was to analyze the inhibitory action of quercetin glycosides by computational docking studies. For this, natural metabolite quercetin glycosides isolated from buckwheat and onions were used as ligand for molecular interaction. The crystallographic structure of molecular target angiotensin-converting enzyme (ACE) (peptidyl-dipeptidase A) was obtained from PDB database (PDB ID: 1O86). Enalapril, a well-known brand of ACE inhibitor was taken as the standard for comparative analysis. Computational docking analysis was performed using PyRx, AutoDock Vina option based on scoring functions. The quercetin showed optimum binding affinity with a molecular target (angiotensin-converting-enzyme) with the binding energy of −8.5 kcal/mol as compared to the standard (−7.0 kcal/mol). These results indicated that quercetin glycosides could be one of the potential ligands to treat hypertension, myocardial infarction, and congestive heart failure. PMID:26109757

  7. 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

  8. 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

  9. 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

  10. 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.

  11. 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

  12. 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

  13. 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

  14. Quercetin-imprinted chromatographic sorbents revisited: optimization of synthesis and rebinding protocols for application to natural resources.

    PubMed

    Pardo, Antonelle; Mespouille, Laetitia; Blankert, Bertrand; Trouillas, Patrick; Surin, Mathieu; Dubois, Philippe; Duez, Pierre

    2014-10-17

    Molecularly imprinted polymers (MIPs) based on quercetin and synthesized by either bulk, precipitation or suspension polymerization were characterized in terms of size and shape by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). After a study of rebinding protocols, the optimal materials were evaluated as sorbents for solid-phase extraction (SPE) and high-performance liquid chromatography (HPLC) to confirm the presence of imprinted cavities and to assess their selectivity. Besides quercetin, other structurally related natural compounds, naringenin, daidzein and curcumin, were employed for selectivity tests of MIPs. Although rebinding protocols previously described for such MIPs are typically based on binding, washing and eluting methanol-based solutions, we show that this highly polar solvent leads to weak specific interactions (imprinting factor<1) and poor sorbent properties, most probably because of hydrogen-bonding interferences between the MIP and MeOH. Similar experiments performed in tetrahydrofuran yield to much more improved properties (imprinting factor>2.4). This calls for reviewing most of previously published data on quercetin-MIPs; in proper binding conditions, published MIPs may prove more performing than initially assessed. As expected, tested MIPs exhibited the highest selective rebinding towards quercetin template (imprinting effect, quercetin, 3.41; naringenin, 1.54; daidzein, 1.38; curcumin, 1.67); the differences in selectivity between quercetin analogues were explained by the ligand geometries and H-bonding patterns obtained from quantum-chemical calculations. The evaluation of MIPs under identical analytical conditions allowed investigating the effect of the production method on chromatographic performances. The MIPs in bead materials (for quercetin, peak width, 0.69; number of theoretical plates, 143; symmetry factor, 2.22) provided a significant improvement in chromatographic efficiency over the bulk materials

  15. Fast-dissolving core-shell composite microparticles of quercetin fabricated using a coaxial electrospray process.

    PubMed

    Li, Chen; Yu, Deng-Guang; Williams, Gareth R; Wang, Zhuan-Hua

    2014-01-01

    This study reports on novel fast-dissolving core-shell composite microparticles of quercetin fabricated using coaxial electrospraying. A PVC-coated concentric spinneret was developed to conduct the electrospray process. A series of analyses were undertaken to characterize the resultant particles in terms of their morphology, the physical form of their components, and their functional performance. Scanning and transmission electron microscopies revealed that the microparticles had spherical morphologies with clear core-shell structure visible. Differential scanning calorimetry and X-ray diffraction verified that the quercetin active ingredient in the core and sucralose and sodium dodecyl sulfate (SDS) excipients in the shell existed in the amorphous state. This is believed to be a result of second-order interactions between the components; these could be observed by Fourier transform infrared spectroscopy. In vitro dissolution and permeation studies showed that the microparticles rapidly released the incorporated quercetin within one minute, and had permeation rates across the sublingual mucosa around 10 times faster than raw quercetin. PMID:24643072

  16. Fast Disintegrating Quercetin-Loaded Drug Delivery Systems Fabricated Using Coaxial Electrospinning

    PubMed Central

    Li, Xiao-Yan; Li, Yan-Chun; Yu, Deng-Guang; Liao, Yao-Zu; Wang, Xia

    2013-01-01

    The objective of this study is to develop a structural nanocomposite of multiple components in the form of core-sheath nanofibres using coaxial electrospinning for the fast dissolving of a poorly water-soluble drug quercetin. Under the selected conditions, core-sheath nanofibres with quercetin and sodium dodecyl sulphate (SDS) distributed in the core and sheath part of nanofibres, respectively, were successfully generated, and the drug content in the nanofibres was able to be controlled simply through manipulating the core fluid flow rates. Field emission scanning electron microscope (FESEM) images demonstrated that the nanofibres prepared from the single sheath fluid and double core/sheath fluids (with core-to-sheath flow rate ratios of 0.4 and 0.7) have linear morphology with a uniform structure and smooth surface. The TEM images clearly demonstrated the core-sheath structures of the produced nanocomposites. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) results verified that quercetin and SDS were well distributed in the polyvinylpyrrolidone (PVP) matrix in an amorphous state, due to the favourite second-order interactions. In vitro dissolution studies showed that the core-sheath composite nanofibre mats could disintegrate rapidly to release quercetin within 1 min. The study reported here provides an example of the systematic design, preparation, characterization and application of a new type of structural nanocomposite as a fast-disintegrating drug delivery system. PMID:24185912

  17. Quercetin as an Antiviral Agent Inhibits Influenza A Virus (IAV) Entry

    PubMed Central

    Wu, Wenjiao; Li, Richan; Li, Xianglian; He, Jian; Jiang, Shibo; Liu, Shuwen; Yang, Jie

    2015-01-01

    Influenza A viruses (IAVs) cause seasonal pandemics and epidemics with high morbidity and mortality, which calls for effective anti-IAV agents. The glycoprotein hemagglutinin of influenza virus plays a crucial role in the initial stage of virus infection, making it a potential target for anti-influenza therapeutics development. Here we found that quercetin inhibited influenza infection with a wide spectrum of strains, including A/Puerto Rico/8/34 (H1N1), A/FM-1/47/1 (H1N1), and A/Aichi/2/68 (H3N2) with half maximal inhibitory concentration (IC50) of 7.756 ± 1.097, 6.225 ± 0.467, and 2.738 ± 1.931 μg/mL, respectively. Mechanism studies identified that quercetin showed interaction with the HA2 subunit. Moreover, quercetin could inhibit the entry of the H5N1 virus using the pseudovirus-based drug screening system. This study indicates that quercetin showing inhibitory activity in the early stage of influenza infection provides a future therapeutic option to develop effective, safe and affordable natural products for the treatment and prophylaxis of IAV infections. PMID:26712783

  18. Fast-Dissolving Core-Shell Composite Microparticles of Quercetin Fabricated Using a Coaxial Electrospray Process

    PubMed Central

    Li, Chen; Yu, Deng-Guang; Williams, Gareth R.; Wang, Zhuan-Hua

    2014-01-01

    This study reports on novel fast-dissolving core-shell composite microparticles of quercetin fabricated using coaxial electrospraying. A PVC-coated concentric spinneret was developed to conduct the electrospray process. A series of analyses were undertaken to characterize the resultant particles in terms of their morphology, the physical form of their components, and their functional performance. Scanning and transmission electron microscopies revealed that the microparticles had spherical morphologies with clear core-shell structure visible. Differential scanning calorimetry and X-ray diffraction verified that the quercetin active ingredient in the core and sucralose and sodium dodecyl sulfate (SDS) excipients in the shell existed in the amorphous state. This is believed to be a result of second-order interactions between the components; these could be observed by Fourier transform infrared spectroscopy. In vitro dissolution and permeation studies showed that the microparticles rapidly released the incorporated quercetin within one minute, and had permeation rates across the sublingual mucosa around 10 times faster than raw quercetin. PMID:24643072

  19. 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

  20. 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

  1. Chemical proteomics identifies heterogeneous nuclear ribonucleoprotein (hnRNP) A1 as the molecular target of quercetin in its anti-cancer effects in PC-3 cells.

    PubMed

    Ko, Chia-Chen; Chen, Yun-Ju; Chen, Chih-Ta; Liu, Yu-Chih; Cheng, Fong-Chi; Hsu, Kai-Chao; Chow, Lu-Ping

    2014-08-01

    Quercetin, a flavonoid abundantly present in plants, is widely used as a phytotherapy in prostatitis and prostate cancer. Although quercetin has been reported to have a number of therapeutic effects, the cellular target(s) responsible for its anti-cancer action has not yet been clearly elucidated. Here, employing affinity chromatography and mass spectrometry, we identified heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) as a direct target of quercetin. A specific interaction between quercetin and hnRNPA1 was validated by immunoblotting and in vitro binding experiments. We found that quercetin bound the C-terminal region of hnRNPA1, impairing the ability of hnRNPA1 to shuttle between the nucleus and cytoplasm and ultimately resulting in its cytoplasmic retention. In addition, hnRNPA1 was recruited to stress granules after treatment of cells with quercetin for up to 48 h, and the levels of cIAP1 (cellular inhibitor of apoptosis), an internal ribosome entry site translation-dependent protein, were reduced by hnRNPA1 regulation. This is the first report that anti-cancer effects of quercetin are mediated, in part, by impairing functions of hnRNPA1, insights that were obtained using a chemical proteomics strategy. PMID:24962584

  2. Silica/quercetin sol-gel hybrids as antioxidant dental implant materials

    NASA Astrophysics Data System (ADS)

    Catauro, Michelina; Papale, Ferdinando; Bollino, Flavia; Piccolella, Simona; Marciano, Sabina; Nocera, Paola; Pacifico, Severina

    2015-06-01

    The development of biomaterials with intrinsic antioxidant properties could represent a valuable strategy for preventing the onset of peri-implant diseases. In this context, quercetin, a naturally occurring flavonoid, has been entrapped at different weight percentages in a silica-based inorganic material by a sol-gel route. The establishment of hydrogen bond interactions between the flavonol and the solid matrix was ascertained by Fourier transform infrared spectroscopy. This technique also evidenced changes in the stretching frequencies of the quercetin dienonic moiety, suggesting that the formation of a secondary product occurs. Scanning electron microscopy was applied to detect the morphology of the synthesized materials. Their bioactivity was shown by the formation of a hydroxyapatite layer on sample surface soaked in a fluid that simulates the composition of human blood plasma. When the potential release of flavonol was determined by liquid chromatography coupled with ultraviolet and electrospray ionization tandem mass spectrometry techniques, the eluates displayed a retention time that was 0.5 min less than quercetin. Collision-activated dissociation mass spectrometry and untraviolet-visible spectroscopy were in accordance with the release of a quercetin derivative. The antiradical properties of the investigated systems were evaluated by DPPH and ABTS methods, whereas the 2,7-dichlorofluorescein diacetate assay highlighted their ability to inhibit the H2O2-induced intracellular production of reactive oxygen species in NIH-3T3 mouse fibroblast cells. Data obtained, along with data gathered from the MTT cytotoxicity test, revealed that the materials that entrapped the highest amount of quercetin showed notable antioxidant effectiveness.

  3. 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

  4. 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.

  5. Minor effects of the citrus flavonoids naringin, naringenin and quercetin, on the pharmacokinetics of doxorubicin in rats.

    PubMed

    Park, Hyun-seo; Oh, Ju-Hee; Lee, Joo hyun; Lee, Young-Joo

    2011-06-01

    We investigated the effects of naringin, naringenin and quercetin on the pharmacokinetics of doxorubicin in rats. These Citrus flavonoids are known as P-glycoprotein (P-gp) inhibitors and thus suspected to interact with doxorubicin, as shown by in vitro cell studies. Plasma concentrations, tissue distribution, and the urinary and biliary excretion of doxorubicin after intravenous infusion were investigated in rats followed by oral administration of Citrus flavonoids. To evaluate the impact of the biotransformation of Citrus flavonoids on the P-gp inhibition, the inhibitory effects of quercetin and its metabolite on P-gp were compared using ex vivo analysis. Contrary to previous in vitro results, the plasma concentration, biliary and urinary clearance, and tissue distribution of doxorubicin were not altered by pre-treatment with naringin and naringenin. Biliary clearance and urinary clearance were slightly decreased by quercetin, but there was no statistical difference. The minor effects of these flavonoids may relate to their low systemic concentration, due to the biotransformation in vivo situation. S9 stability assay and calcein accumulation assay showed that quercetin was a metabolically unstable compound, and the inhibitory effect of its metabolites on P-gp was negligible. In conclusion, naringin, naringenin and quercetin did not affect the in vivo pharmacokinetics of intravenously administered doxorubicin. PMID:21699081

  6. Evaluation of inhibitory effects of caffeic acid and quercetin on human liver cytochrome p450 activities.

    PubMed

    Rastogi, Himanshu; Jana, Snehasis

    2014-12-01

    When herbal drugs and conventional allopathic drugs are used together, they can interact in our body which can lead to the potential for herb-drug interactions. This work was conducted to evaluate the herb-drug interaction potential of caffeic acid and quercetin mediated by cytochrome P450 (CYP) inhibition. Human liver microsomes (HLMs) were added to each selective probe substrates of cytochrome P450 enzymes with or without of caffeic acid and quercetin. IC50 , Ki values, and the types of inhibition were determined. Both caffeic acid and quercetin were potent competitive inhibitors of CYP1A2 (Ki = 1.16 and 0.93 μM, respectively) and CYP2C9 (Ki = 0.95 and 1.67 μM, respectively). Caffeic acid was a potent competitive inhibitor of CYP2D6 (Ki = 1.10 μM) and a weak inhibitor of CYP2C19 and CYP3A4 (IC50  > 100 μM). Quercetin was a potent competitive inhibitor of CYP 2C19 and CYP3A4 (Ki = 1.74 and 4.12 μM, respectively) and a moderate competitive inhibitor of CYP2D6 (Ki = 18.72 μM). These findings might be helpful for safe and effective use of polyphenols in clinical practice. Our data indicated that it is necessary to study the in vivo interactions between drugs and pharmaceuticals with dietary polyphenols. PMID:25196644

  7. 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

  8. 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

  9. Quercetin derivatives as novel antihypertensive agents: Synthesis and physiological characterization.

    PubMed

    Grande, Fedora; Parisi, Ortensia I; Mordocco, Roberta A; Rocca, Carmine; Puoci, Francesco; Scrivano, Luca; Quintieri, Anna M; Cantafio, Patrizia; Ferla, Salvatore; Brancale, Andrea; Saturnino, Carmela; Cerra, Maria C; Sinicropi, Maria S; Angelone, Tommaso

    2016-01-20

    The antihypertensive flavonol quercetin (Q1) is endowed with a cardioprotective effect against myocardial ischemic damage. Q1 inhibits angiotensin converting enzyme activity, improves vascular relaxation, and decreases oxidative stress and gene expression. However, the clinical application of this flavonol is limited by its poor bioavailability and low stability in aqueous medium. In the aim to overcome these drawbacks and preserve the cardioprotective effects of quercetin, the present study reports on the preparation of five different Q1 analogs, in which all OH groups were replaced by hydrophobic functional moieties. Q1 derivatives have been synthesized by optimizing previously reported procedures and analyzed by spectroscopic analysis. The cardiovascular properties of the obtained compounds were also investigated in order to evaluate whether chemical modification affects their biological efficacy. The interaction with β-adrenergic receptors was evaluated by molecular docking and the cardiovascular efficacy was investigated on the ex vivo Langendorff perfused rat heart. Furthermore, the bioavailability and the antihypertensive properties of the most active derivative were evaluated by in vitro studies and in vivo administration (1month) on spontaneously hypertensive rats (SHRs), respectively. Among all studied Q1 derivatives, only the ethyl derivative reduced left ventricular pressure (at 10(-8)M÷10(-6)M doses) and improved relaxation and coronary dilation. NOSs inhibition by L-NAME abolished inotropism, lusitropism and coronary effects. Chronic administration of high doses of this compound on SHR reduced systolic and diastolic pressure. Differently, the acetyl derivative induced negative inotropism and lusitropism (at 10(-10)M and 10(-8)÷10(-6)M doses), without affecting coronary pressure. Accordingly, docking studies suggested that these compounds bind both β1/β2-adrenergic receptors. Taking into consideration all the obtained results, the replacement of

  10. New Treatment of Medullary and Papillary Human Thyroid Cancer: Biological Effects of Hyaluronic Acid Hydrogel Loaded With Quercetin Alone or in Combination to an Inhibitor of Aurora Kinase.

    PubMed

    Quagliariello, Vincenzo; Armenia, Emilia; Aurilio, Caterina; Rosso, Francesco; Clemente, Ottavia; de Sena, Gabriele; Barbarisi, Manlio; Barbarisi, Alfonso

    2016-08-01

    The aim of this paper is based on the use of a hyaluronic acid hydrogel of Quercetin tested alone and in combination to an inhibitor of Aurora Kinase type A and B (SNS-314) on human medullary and papillary thyroid cancer cells. Biological investigations were focused on the cellular uptake of the hydrogel, cell viability, antioxidant, and cytokines secretion studies. Quercetin delivered from hydrogel show a time and CD44 dependent interaction with both cell lines with significant anti-inflammatory effects. Combination of Quercetin and SNS-314 leads to a synergistic cytotoxic effect on medullary TT and papillary BCPAP cell lines with a significant reduction of the IC50 value. These results, highlights the importance of synergistic effect of the hyaluronic acid hydrogel of Quercetin with SNS-314 in the regulation of human thyroid cancer cell proliferation and emphasize the anti-tumor activity of these molecules. J. Cell. Physiol. 231: 1784-1795, 2016. © 2015 Wiley Periodicals, Inc. PMID:26660542

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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.

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

    PubMed

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

    1999-12-01

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

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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

  4. Design and characterization of protein-quercetin bioactive nanoparticles

    PubMed Central

    2011-01-01

    Background The synthesis of bioactive nanoparticles with precise molecular level control is a major challenge in bionanotechnology. Understanding the nature of the interactions between the active components and transport biomaterials is thus essential for the rational formulation of bio-nanocarriers. The current study presents a single molecule of bovine serum albumin (BSA), lysozyme (Lys), or myoglobin (Mb) used to load hydrophobic drugs such as quercetin (Q) and other flavonoids. Results Induced by dimethyl sulfoxide (DMSO), BSA, Lys, and Mb formed spherical nanocarriers with sizes less than 70 nm. After loading Q, the size was further reduced by 30%. The adsorption of Q on protein is mainly hydrophobic, and is related to the synergy of Trp residues with the molecular environment of the proteins. Seven Q molecules could be entrapped by one Lys molecule, 9 by one Mb, and 11 by one BSA. The controlled releasing measurements indicate that these bioactive nanoparticles have long-term antioxidant protection effects on the activity of Q in both acidic and neutral conditions. The antioxidant activity evaluation indicates that the activity of Q is not hindered by the formation of protein nanoparticles. Other flavonoids, such as kaempferol and rutin, were also investigated. Conclusions BSA exhibits the most remarkable abilities of loading, controlled release, and antioxidant protection of active drugs, indicating that such type of bionanoparticles is very promising in the field of bionanotechnology. PMID:21586116

  5. 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

  6. Detection of quercetin based on Al(3+)-amplified phosphorescence signals of manganese-doped ZnS quantum dots.

    PubMed

    Zhang, Zhifeng; Miao, Yanming; Lian, Linwang; Yan, Guiqin

    2015-11-15

    A simple phosphorescence method is proposed for quercetin detection based on Al(3+)-amplified room-temperature phosphorescence (RTP) signals of 3-mercaptopropionic acid (MPA)-capped Mn-doped ZnS quantum dots (QDs). The sensor was established based on some properties as follows. Al(3+) can interact with carboxyl groups on the surface of MPA-capped Mn-doped ZnS QDs via chelation, which will lead to the aggregation of QDs and amplification of RTP signals, After the addition of quercetin, it can form more stable complex with Al(3+) in alkaline aqueous solution and dissociate Al(3+) from the surface of Mn-doped ZnS QDs, which will result in significant recovery of RTP intensity of the MPA-capped Mn-doped ZnS-Al(3+) system. Under the optimized conditions, the change of RTP intensity was proportional to the concentration of quercetin in the range from 0.1 to 6.0 mg L(-1), with a high correlation coefficient of 0.996 and a detection limit of 0.047 mg L(-1). The proposed method is potentially suitable for detection of quercetin in real samples without complicated pretreatment. PMID:26278167

  7. Sol-gel synthesis and characterization of SiO2/PCL hybrid materials containing quercetin as new materials for antioxidant implants.

    PubMed

    Catauro, Michelina; Bollino, Flavia; Papale, Ferdinando; Piccolella, Simona; Pacifico, Severina

    2016-01-01

    The development of biomaterials with intrinsic antioxidant properties could represent a valuable strategy for preventing peri-implant disease onset. In this context quercetin, a naturally occurring flavonoid, has been entrapped, at different weight percentages in a silica/poly(ε-caprolactone)-based hybrid material by a sol-gel route. FT-IR and UV spectroscopic techniques were employed in order to characterize the hybrids. FT-IR analysis indicated changes in stretching frequencies of the quercetin dienonic moiety, suggesting that a flavonol oxidized derivative was formed during the sol-gel process. The establishment of hydrogen-bonded interactions between quercetin and silica and polymer matrices,was strongly affected by the amount of polymer. Poly(ε-caprolactone) did not interact with quercetin when it was loaded at high doses (50 wt.%). The morphology of the synthesized materials was observed by using SEM. The obtained images proved that the materials are hybrid nanocomposites. Their bioactivity was shown by the formation of a hydroxyapatite layer on samples' surface soaked in a fluid simulating the composition of the human plasma. The antiradical properties of the investigated systems were evaluated by DPPH and ABTS methods and their cytotoxicity by the MTT assay. Data obtained revealed that the synthesized materials are biocompatible and that the hybrid system,with 6 wt.% of PCL and 15 wt.% of quercetin, produced the strongest antiradical efficacy. PMID:26478390

  8. 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

  9. Quercetin 3-O-rutinoside mediated inhibition of PBP2a: computational and experimental evidence to its anti-MRSA activity.

    PubMed

    Rani, Nidhi; Vijayakumar, Saravanan; Thanga Velan, Lakshmi Palanisamy; Arunachalam, Annamalai

    2014-12-01

    The PBP2a is a cell wall synthesizing protein, which causes resistivity in methicillin resistant Staphylococcus aureus (MRSA) from β-lactam antibiotics but it is susceptible to 5th generation cephalosporin, ceftobiprole. Ceftobiprole inhibits the growth of MRSA by targeting the PBP2a-mediated cell wall synthesis, but it is reported to have adverse side effects. Due to this, there is a constant need to develop natural alternatives, which are generally free from adverse side effects. Hence in this study, in silico based docking analysis was performed with 37 quercetin derivatives towards PBP2a inhibition and their efficiencies were compared with β-lactam antibiotic, ceftobiprole. The docking studies suggested that quercetin 3-O-rutinoside (ZINC5280805) interacted efficiently with PBP2a, attaining the highest LibDock score (187.32) compared to other quercetin derivatives. The structural stability and dynamics of the identified lead with PBP2a were validated through molecular dynamics simulation. Simulation results such as RMSD, RMSF, and Rg values indicated that the stability of quercetin 3-O-rutinoside with PBP2a was better, with respect to the un-ligated PBP2a. Furthermore, the quercetin 3-O-rutinoside was subjected to an antibacterial susceptibility test and found to have antibacterial activity at 500, 700, and 900 μM concentration. Also, morphological changes in the bacterial colony and bacterial surface were observed using a scanning electron microscope, when MRSA was treated with 900 μM concentration of quercetin 3-O-rutinoside. Collectively, results from this study suggest that the quercetin 3-O-rutinoside has the capability to inhibit PBP2a and hence could be used as an alternative or in combination with other drugs in treating MRSA infection. PMID:25286279

  10. Anti Proliferative and Pro Apoptotic Effects of Flavonoid Quercetin Are Mediated by CB1 Receptor in Human Colon Cancer Cell Lines.

    PubMed

    Refolo, Maria Grazia; D'Alessandro, Rosalba; Malerba, Natascia; Laezza, Chiara; Bifulco, Maurizio; Messa, Caterina; Caruso, Maria Gabriella; Notarnicola, Maria; Tutino, Valeria

    2015-12-01

    Quercetin, the major constituent of flavonoid and widely present in fruits and vegetables, is an attractive compound for cancer prevention due to its beneficial anti proliferative effects, showing a crucial role in the regulation of apoptosis and cell cycle signaling. In vitro studies have demonstrated that quercetin specifically influences colon cancer cell proliferation. Our experiments, using human colon adenocarcinoma cells, confirmed the anti proliferative effect of quercetin and gave intriguing new insight in to the knowledge of the mechanisms involved. We observed a significant increase in the expression of the endocannabinoids receptor (CB1-R) after quercetin treatment. CB1-R can be considered an estrogen responsive receptor and quercetin, having a structure similar to that of the estrogens, can interact with CB1-R leading to the regulation of cell growth. In order to clarify the contribution of the CB1-R to the quercetin action, we investigated some of the principal molecular pathways that are inhibited or activated by this natural compound. In particular we detected the inhibition of the major survival signals like the PI3K/Akt/mTOR and an induction of the pro apoptotic JNK/JUN pathways. Interestingly, the metabolism of β-catenin was modified by flavonoid both directly and through activated CB1-R. In all the experiments done, the quercetin action has proven to be reinforced by anandamide (Met-F-AEA), a CB1-R agonist, and partially counteracted by SR141716, a CB1-R antagonist. These findings open new perspectives for anticancer therapeutic strategies. PMID:25893829

  11. 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

  12. Investigation of function similarities between the sarcoplasmic reticulum and platelet calcium-dependent adenosinetriphosphatases with the inhibitors quercetin and calmidazolium

    SciTech Connect

    Fischer, T.H.; Campbell, K.P.; White, G.C. II

    1987-12-01

    The platelet and skeletal sarcoplasmic reticulum calcium-dependent adenosinetriphosphatases (Ca/sup 2 +/-ATPases) were functionally compared with respect to substrate activation by steady-state kinetic methods using the inhibitors quercetin and calmidazolium. Quercetin inhibited platelet and sarcoplasmic reticulum Ca/sup 2 +/-ATPase activities in a dose-dependent manner with IC/sub 50/ values of 25 and 10 ..mu..M, respectively. Calmidazolium also inhibited platelet and sarcoplasmic reticulum Ca/sup 2 +/-ATPase activities, with half-maximal inhibition measured at 5 and 4 ..mu..M, respectively. Both inhibitors also affected the (/sup 45/Ca) calcium transport activity of intact platelet microsomes at concentrations similar to those which reduced Ca/sup 2 +/-ATPase activity. These inhibitors were then used to examine substrate ligation by the platelet and sarcoplasmic reticulum calcium pump proteins. For both Ca/sup 2 +/-ATPase proteins, quercetin has an affinity for the E-Ca/sub 2/ (fully ligated with respect to calcium at the exterior high-affinity calcium binding sites, unligated with respect to ATP) conformational state of the protein that is approximately 10-fold grater than for other conformational states in the hydrolytic cycle. Quercetin can thus be considered a competitive inhibitor of the calcium pump proteins with respect to ATP. In contrast to the effect of quercetin, calmidazolium interacts with the platelet and sarcoplasmic reticulum Ca/sup 2 +/-ATPases in an uncompetitive manner. The dissociation constants for this inhibitor for the different conformational states of the calcium pump proteins were similar, indicating that calmidazolium has equal affinity for all of the reaction intermediates probed. These observations indicate that the substrate ligation processes are similar for the two pump proteins. This supports the concept that the hydrolytic cycles of the two proteins are comparable.

  13. Computational studies of the regioselectivities of COMT-catalyzed meta-/para-O methylations of luteolin and quercetin.

    PubMed

    Cao, Yang; Chen, Zhong-Jian; Jiang, Hui-Di; Chen, Jian-Zhong

    2014-01-16

    Catechol-O-methyltransferase (COMT, EC 2.1.1.6) plays a central role in the inactivation of neurotransmitters sharing a catecholic motif by transferring a methyl group from AdoMet. Methylation of the meta-hydroxyl is much more common than that of the para-hydroxyl in many COMT substrates, such as dopamine and norepinephrine. Our experimental data showed that quercetin preferred meta-methylation but luteolin favored a para-methylation. To elucidate the mechanism for different preferences of methylations of quercetin and luteolin, we performed a theoretical investigation on the different regioseletivities of COMT-catalyzed methylations for quercetin and luteolin by a combined approach of MD simulations, ab initio calculations, and QM/MM computations. The ab initio calculation results showed that both quercetin and luteolin have more negative charge distributions on the meta-O atom than the para-O atom, which indicated that meta-O preferred SN2 reaction for their methylation. Our QM/MM computations also confirmed that these two flavonoids have lower reaction energetic barriers for COMT-catalyzed meta-O-methylation than para-O-methylation. On the other hand, our binding free energy computation results indicated that quercetin has a more stable binding mode for meta-O-methylation than para-O-methylation but luteolin has a more stable binding mode for para-O-methylation than meta-O-methylation. We gave a comprehensive explanation considering both thermodynamics and reaction kinetics aspects and discussed the protein-inhibitor interactions as well as the O-methylation mechanism in our present work. PMID:24354565

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

  2. Quercetin as natural stabilizing agent for bio-polymer

    NASA Astrophysics Data System (ADS)

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

    2014-05-01

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

  3. Quercetin as natural stabilizing agent for bio-polymer

    SciTech Connect

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

    2014-05-15

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

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

    PubMed

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

    2015-12-01

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

  5. Enzymatic modification of chitosan with quercetin and its application as antioxidant edible films.

    PubMed

    Torres, E; Marín, V; Aburto, J; Beltrán, H I; Shirai, K; Villanueva, S; Sandoval, G

    2012-01-01

    Quercetin, rutin, naringin, hesperidin and chrysin were tested as substrates for chloroperoxidase to produce reactive quinones to graft onto chitosan. Quercetin and rutin quinones were successfully chemically attached to low molecular weight chitosan. The quercetin-modified chitosan showed an enhancement of plastic, antioxidant and antimicrobial properties as well as of thermal degradability. Finally, chitosan-quercetin films visibly decreased enzymatic oxidation when applied to Opuntia ficus indica cladodes. PMID:22586910

  6. Preparation Of Gold Nanoparticle-Quercetin Complexes By Citrate Reduction Method

    NASA Astrophysics Data System (ADS)

    Pal, Rajat; Chakraborti, Abhay Sankar

    2010-10-01

    Quercetin is an important flavonoid and possesses strong antioxidant property. The aim of the present study is to formulate and characterize quercetin coated gold nanoparticles. Quercetin was conjugated with gold nanoparticle during synthesis of the particle by citrate reduction of chloroauric acid. The conjugates were characterized by different techniques like Atomic Force Microscopy, Dynamic Light Scattering, Transmission Electron Microscopy, Absorption Spectroscopy, Differential Scanning Calorimetry and Thermal Gravimetric Analysis. All these studies suggest formation of stable quercetin-gold nanoparticle complex.

  7. Synthesis and Anti-Proliferative Effects of Quercetin Derivatives.

    PubMed

    Al-Jabban, Sami M R; Zhang, Xiaojie; Chen, Guanglin; Mekuria, Ermias Addo; Rakotondraibe, Liva Harinantenaina; Chen, Qiao-Hong

    2015-12-01

    Prostate cancer is the most common diagnosed invasive cancer in American men and is the second leading cause of cancer-related deaths. Although there are several therapies successful in treating early, localized stage prostate cancer, current treatment of advanced metastatic castration-resistant prostate cancer remains ineffective due to inevitable progression of resistance to first-line treatment with docetaxel. The natural product quercetin (3,3',4',5,7-pentahydroxyflavone), a flavonoid compound ubiquitous in dietary plants, possesses evidenced potential in treating advanced metastatic castration-resistant prostate cancer. However, its poor bioavailability and moderate potency hinder its advancement into clinical therapy. In order to engineer quercetin derivatives with improved potency and pharmacokinetic profiles for the treatment of advanced metastatic prostate cancer, we started this study with creating a small library of alkylated derivatives of quercetin for in vitro evaluation. The biological data and chemical reactivity of quercetin and its derivatives reported in literature directed us to design 3,4',7-O-trialkylquercetins as our first batch of targets. Consequently, nine 3,4',7-O-trialkylquercetins, together with four 3,7-O- dialkylquercetins, four 3,3',4',7-tetraalkylquercetins, and one 3,3',4'-O-trialkylquercetin, were prepared by one step O-alkylation of commercially available quercetin mediated by potassium carbonate. Their structures were determined by ID and 2D NMR data, and HRMS. Their anti-proliferative activities towards both androgen-refractory and androgen-sensitive prostate cancer cells were evaluated using WST-1 cell proliferation assay. The acquired structure-activity relationships indicate that 3,7-O-dialkylquercetins rather than 3,4',7-O-trialkylquercetins were much more potent than quercetin towards prostate cancer cells. PMID:26882678

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

    PubMed Central

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

    2010-01-01

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

  9. Damage and protection of the photosynthetic apparatus from UV-B radiation. II. Effect of quercetin at different pH.

    PubMed

    Dobrikova, Anelia G; Apostolova, Emilia L

    2015-07-20

    The effect of the exogenously added quercetin against the UV-B inhibition of the photosystem II (PSII) functions in isolated pea thylakoid membranes suspended at different pH of the medium (6.5, 7.6 and 8.4) was investigated. The data revealed that the interaction of this flavonoid with the membranes depends on the pH and influences the initial S0-S1 state distribution of PSII in the dark, the energy transfer between pigment-protein complexes of the photosynthetic apparatus and the membrane fluidity. Quercetin also displays a different UV-protective effect depending on its location in the membranes, as the effect is more pronounced at pH 8.4 when it is located at the membrane surface. The results suggest that quercetin induces structural changes in thylakoid membranes, one of the possible reasons for its protection of the photosynthetic apparatus. PMID:26282614

  10. Comparison of methods for rapid analysis of quercetin.

    PubMed

    Pardo-Barrela, Jessica; Lago-Crespo, Miguel; Lage-Yusty, María Asunción; López-Hernández, Julia

    2015-03-01

    Quercetin is a polyphenol of growing interest that is present in many foods. In this study, we compared two methods for its determination in samples of drinks made of juice and in dietary supplements, one chromatographic (HPLC) and other spectrofluorimetric (constant-wavelength synchronous spectrofluorimetry). To confirm the identification of the quercetin in the samples an HPLC-PDA-MS/MS system was used. It was concluded that both methods are suitable for dietary supplements and the choice of one or the other depends on the type of sample, time available for the analysis as well as the available resources. For juice beverages only HPLC is suitable. PMID:25488586

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

    PubMed

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

    2013-03-01

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

  12. Estimated Daily Intake and Seasonal Food Sources of Quercetin in Japan

    PubMed Central

    Nishimuro, Haruno; Ohnishi, Hirofumi; Sato, Midori; Ohnishi-Kameyama, Mayumi; Matsunaga, Izumi; Naito, Shigehiro; Ippoushi, Katsunari; Oike, Hideaki; Nagata, Tadahiro; Akasaka, Hiroshi; Saitoh, Shigeyuki; Shimamoto, Kazuaki; Kobori, Masuko

    2015-01-01

    Quercetin is a promising food component, which can prevent lifestyle related diseases. To understand the dietary intake of quercetin in the subjects of a population-based cohort study and in the Japanese population, we first determined the quercetin content in foods available in the market during June and July in or near a town in Hokkaido, Japan. Red leaf lettuce, asparagus, and onions contained high amounts of quercetin derivatives. We then estimated the daily quercetin intake by 570 residents aged 20–92 years old in the town using a food frequency questionnaire (FFQ). The average and median quercetin intakes were 16.2 and 15.5 mg day−1, respectively. The quercetin intakes by men were lower than those by women; the quercetin intakes showed a low correlation with age in both men and women. The estimated quercetin intake was similar during summer and winter. Quercetin was mainly ingested from onions and green tea, both in summer and in winter. Vegetables, such as asparagus, green pepper, tomatoes, and red leaf lettuce, were good sources of quercetin in summer. Our results will help to elucidate the association between quercetin intake and risks of lifestyle-related diseases by further prospective cohort study and establish healthy dietary requirements with the consumption of more physiologically useful components from foods. PMID:25849945

  13. Quercetin Suppresses Twist to Induce Apoptosis in MCF-7 Breast Cancer Cells

    PubMed Central

    Ranganathan, Santhalakshmi; Halagowder, Devaraj; Sivasithambaram, Niranjali Devaraj

    2015-01-01

    Quercetin is a dietary flavonoid which exerts anti-oxidant, anti-inflammatory and anti-cancer properties. In this study, we investigated the anti-proliferative effect of quercetin in two breast cancer cell lines (MCF-7 and MDA-MB-231), which differed in hormone receptor. IC50 value (37μM) of quercetin showed significant cytotoxicity in MCF-7 cells, which was not observed in MDA-MB-231 cells even at 100μM of quercetin treatment. To study the response of cancer cells to quercetin, with respect to different hormone receptors, both the cell lines were treated with a fixed concentration (40μM) of quercetin. MCF-7 cells on quercetin treatment showed more apoptotic cells with G1 phase arrest. In addition, quercetin effectively suppressed the expression of CyclinD1, p21, Twist and phospho p38MAPK, which was not observed in MDA-MB-231 cells. To analyse the molecular mechanism of quercetin in exerting an apoptotic effect in MCF-7 cells, Twist was over-expressed and the molecular changes were observed after quercetin administration. Quercetin effectively regulated the expression of Twist, in turn p16 and p21 which induced apoptosis in MCF-7 cells. In conclusion, quercetin induces apoptosis in breast cancer cells through suppression of Twist via p38MAPK pathway. PMID:26491966

  14. Estimated daily intake and seasonal food sources of quercetin in Japan.

    PubMed

    Nishimuro, Haruno; Ohnishi, Hirofumi; Sato, Midori; Ohnishi-Kameyama, Mayumi; Matsunaga, Izumi; Naito, Shigehiro; Ippoushi, Katsunari; Oike, Hideaki; Nagata, Tadahiro; Akasaka, Hiroshi; Saitoh, Shigeyuki; Shimamoto, Kazuaki; Kobori, Masuko

    2015-04-01

    Quercetin is a promising food component, which can prevent lifestyle related diseases. To understand the dietary intake of quercetin in the subjects of a population-based cohort study and in the Japanese population, we first determined the quercetin content in foods available in the market during June and July in or near a town in Hokkaido, Japan. Red leaf lettuce, asparagus, and onions contained high amounts of quercetin derivatives. We then estimated the daily quercetin intake by 570 residents aged 20-92 years old in the town using a food frequency questionnaire (FFQ). The average and median quercetin intakes were 16.2 and 15.5 mg day(-1), respectively. The quercetin intakes by men were lower than those by women; the quercetin intakes showed a low correlation with age in both men and women. The estimated quercetin intake was similar during summer and winter. Quercetin was mainly ingested from onions and green tea, both in summer and in winter. Vegetables, such as asparagus, green pepper, tomatoes, and red leaf lettuce, were good sources of quercetin in summer. Our results will help to elucidate the association between quercetin intake and risks of lifestyle-related diseases by further prospective cohort study and establish healthy dietary requirements with the consumption of more physiologically useful components from foods. PMID:25849945

  15. Optimization of β-cyclodextrin cross-linked polymer for monitoring of quercetin

    NASA Astrophysics Data System (ADS)

    Zhu, Xiashi; Ping, Wenhui

    2014-11-01

    A novel method for the separation/analysis of quercetin was described, which was based on the investigation of the inclusion interactions of β-cyclodextrin cross-linked polymer (β-CDCP) with quercetin (Qu) and the adsorption behavior of Qu on β-CDCP. The inclusion interaction of β-CDCP with Qu was studied through FTIR, TGA and 13C NMR. Under the optimum conditions, the preconcentration factor of the proposed method was approximately 8.8, the β-CDCP could be used repeatedly for 30 times and offered better recovery. The linear range, limit of detection (LOD) and the relative standard deviation (RSD) was found to be 0.10-12.0 μg mL-1, 4.6 ng mL-1 and 3.10% (n = 3, c = 2.0 μg mL-1) respectively. This technique had been successfully applied to the determination of Qu in real samples.

  16. Ameliorating effect of quercetin on acute pentylenetetrazole induced seizures in rats

    PubMed Central

    Sefil, Fatih; Kahraman, Ibrahim; Dokuyucu, Recep; Gokce, Hasan; Ozturk, Atakan; Tutuk, Okan; Aydin, Mehmet; Ozkan, Umit; Pinar, Neslihan

    2014-01-01

    Objective: The aim of the study to elicit effects of pure quercetin in pentylenetetrazole (PTZ) and picrotoxin induced seizures. Materials and methods: Each animal group was divided into six groups and composed of six rats. Rats were assigned to the following experiments and groups (G): (G1) PTZ 45 mg/kg + DMSO; (G2) PTZ 45 mg/kg + 5 mg/kg quercetin; (G3) PTZ 45 mg/kg + 10 mg/kg quercetin; (G4) PTZ 45 mg/kg + 20 mg/kg quercetin; (G5) PTZ 45 mg/kg + 40 mg/kg quercetin; (G6) Picrotoxin 5 mg/kg + DMSO; (G7) Picrotoxin 5 mg/kg + 10 mg/kg quercetin; (G8) Picrotoxin 5 mg/kg + 20 mg/kg quercetin. In all groups quercetin were injected 30 min before PTZ and picrotoxin applications. Results: Compared to PTZ, quercetin significantly prolonged onset of the seizure in 10 mg/kg (P < 0.05) and reduced the seizure stage in 10 mg/kg quercetin injected group (P < 0.01). Compared to PTZ, quercetin also declined the generalized seizure duration at 10 mg/kg (P < 0.01) and 20 mg/kg (P < 0.05) doses. At the doses of 5 mg/kg and 40 mg/kg quercetin there were no significant changes in seizure parameters. Development of picrotoxin induced seizures is slower than in PTZ. Quercetin was found to be unable to prevent seizure in picrotoxin induced seizures. Surprisingly, quercetin also significantly reduced the onset of seizures at the dose of 20 mg/kg (P < 0.05). Conclusion: quercetin (at doses of 10 and 20 mg/kg i.p) prevented seizures in PTZ (45 mg/kg i.p) induced seizures. Especially, 10 mg/kg PTZ prolonged onset of seizures, reduced the seizure duration and seizure severity score in comparison with control group. At a higher (40 mg/kg) dose quercetin failed to prevent PTZ induced seizures. In addition 20 mg/kg quercetin significantly reduced the onset of seizures that suggest a preconvulsive effect. 20 mg/kg quercetin reduced the onset of picrotoxin induced seizures. In picrotoxin model, it may be claimed that quercetin at higher doses accelerate the epileptic activity owing to its

  17. Quercetin blocks t-AUCB-induced autophagy by Hsp27 and Atg7 inhibition in glioblastoma cells in vitro.

    PubMed

    Li, Junyang; Tang, Chao; Li, Liwen; Li, Rujun; Fan, Youwu

    2016-08-01

    We previously demonstrated that the acquired resistance because of Hsp27 activation weakens the cytotoxic effect of t-AUCB on glioblastoma cells. Since autophagy is regarded as a survival mechanism for cells exposed to cytotoxic agents, the aim of this study is to investigate whether t-AUCB induces autophagy and whether Hsp27 and autophagy are interacted with each other. Our data demonstrated that t-AUCB induces autophagy in glioblastoma cells and regulates multiple autophagy related-gene expression. t-AUCB induces overexpression of Atg7, which is downstream of Hsp27 and participates in the resistance of glioblastoma cells to t-AUCB treatment. Hsp27 inhibitor quercetin suppresses Atg7 expression and strengthens t-AUCB-induced cell death by autophagy blockage. We concluded that combination of quercetin and t-AUCB might be a potential strategy for glioblastoma treatment. PMID:27174198

  18. Quercetin as colorimetric reagent for determination of zirconium

    USGS Publications Warehouse

    Grimaldi, F.S.; White, C.E.

    1953-01-01

    Methods described in the literature for the determination of zirconium are generally designed for relatively large amounts of this element. A good procedure using colorimetric reagent for the determination of trace amounts is desirable. Quercetin has been found to yield a sensitive color reaction with zirconium suitable for the determination of from 0.1 to 50?? of zirconium dioxide. The procedure developed involves the separation of zirconium from interfering elements by precipitation with p-dimethylaminoazophenylarsonic acid prior to its estimation with quercetin. The quercetin reaction is carried out in 0.5N hydrochloric acid solution. Under the operating conditions it is indicated that quercetin forms a 2 to 1 complex with zirconium; however, a 2 to 1 and a 1 to 1 complex can coexist under special conditions. Approximate values for the equilibrium constants of the complexes are K1 = 0.33 ?? 10-5 and K2 = 1.3 ?? 10-9. Seven Bureau of Standards samples of glass sands and refractories were analyzed with excellent results. The method described should find considerable application in the analysis of minerals and other materials for macro as well as micro amounts of zirconium.

  19. DFT study of glycosyl group reactivity in quercetin derivatives

    NASA Astrophysics Data System (ADS)

    Jeevitha, D.; Sadasivam, K.; Praveena, R.; Jayaprakasam, R.

    2016-09-01

    Density functional theory (DFT) is used to compute relevant electronic properties with the purpose of generating precise information which facilitates the best activity given by the positions of glycosyl group attached at all 3 different rings of quercetin such as Q3G (C- ring), Q7G (A-ring) and Q3‧G (B-ring). Computed values of the OH BDE, frontier molecular orbitals (FMOs), molecular electrostatic potential (MEP), Density of states (DOS,PDOS,OPDOS) and electronic properties such as electron affinity (EA), ionization potential (IP), softness (S), hardness (η), electronegativity (χ) and electrophilic index (ω) indicate that the title compounds possess good radical scavenging activity. Charge delocalization and intramolecular hydrogen bonds are characterized using natural bond orbital (NBO) analysis. NBO accurately differentiate the weak and strong intramolecular hydrogen bond of quercetin-O-glycoside compounds. Results available from the computational investigation have proved that A-ring glycoside of quercetin is capable of donating electrons and acts as a good anti-oxidant than B-ring glycoside and C-ring glycoside of quercetin.

  20. 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

  1. 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.

  2. Stabilization of quercetin flavonoid in MCM-41 mesoporous silica: positive effect of surface functionalization.

    PubMed

    Berlier, Gloria; Gastaldi, Lucia; Ugazio, Elena; Miletto, Ivana; Iliade, Patrizia; Sapino, Simona

    2013-03-01

    Antioxidants can prevent UV-induced skin damage mainly by neutralizing free radicals. For this purpose, quercetin (Q) is one of the most employed flavonoids even if the potential usefulness is limited by its unfavorable physicochemical properties. In this context, mesoporous silica (MCM-41) is herein proposed as a novel vehicle able to improve the stability and performance of this phenolic substrate in topical products. Complexes of Q with plain or octyl-functionalized MCM-41 were successfully prepared with different weight ratios by a kneading method, and then, they were characterized by XRD, gas-volumetric (BET), TGA, DSC, and FTIR analyses. The performances of the different complexes were evaluated in vitro in terms of membrane diffusion profiles, storage and photostability, antiradical and chelating activities. The physicochemical characterization confirmed an important host/guest interaction due to the formation of Si-OH/quercetin hydrogen-bonded adducts further strengthened by octyl functionalization through van der Waals forces. The immobilization of Q, particularly on octyl-functionalized silica, increased the stability without undermining the antioxidant efficacy opening the way for an innovative employment of mesoporous composite materials in the skincare field. PMID:23245887

  3. 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

  4. Assessment of the reactivity of selected isoflavones against proteins in comparison to quercetin.

    PubMed

    Rawel, Harshadrai M; Ranters, Holger; Rohn, Sascha; Kroll, Jürgen

    2004-08-11

    Selected isoflavones (genistein, daidzein, formononetin, prunetin, biochanin A, and two synthetic isoflavones) were allowed to interact with soy and whey proteins. The reaction products were analyzed in terms of covalent binding at the nucleophilic side chains of proteins. Changes in molecular properties of the proteins derivatives were documented by SDS-PAGE, IEF, and SELDI-TOF-MS. The structural changes induced were studied using circular dichroism. The in vitro digestibility was assessed with trypsin. The results show that the occurrence of the catechol moiety, that is, the two adjacent (ortho) aromatic hydroxyl groups on ring B of the flavonoid structural skeleton appears to be prerequisite condition for covalent binding to proteins. The catechol moiety on ring A was less reactive. Its absence lead to a slight or no significant reaction, although noncovalent interactions may still be possible, even when lacking this structural element. A comparison of the data is also made with quercetin representing the flavonols. PMID:15291506

  5. Study of fluorescence quenching mechanism between quercetin and tyrosine-H 2O 2-enzyme catalyzed product

    NASA Astrophysics Data System (ADS)

    Zhang, Miao; Lv, Qingluan; Yue, Ningning; Wang, Huaiyou

    2009-04-01

    Because of catalysis of horseradish peroxidase, the tyrosine reacted with H 2O 2 to form the product S which was a strong fluorescence substance. To the product S, the quercetin was acted as a quencher. The fluorescence quenching mechanism was studied by the measurement of fluorescence lifetime and based on the Stern-Volmer plot. The reaction mechanism, which was the static quenching process between quercetin and product S, was studied. The binding constant, K = 4.03 × 10 5 L mol -1 and the number of binding sites n = 1.09, were obtained against this reaction. The thermodynamic parameters were estimated. The data, Δ H = -75.68 kJ mol -1, Δ S = -147.9 J K -1 mol -1 and Δ G = -29.17 kJ mol -1 showed that the reaction was spontaneous and exothermic. What is more, both Δ H and Δ S were negative values indicated that van der Waals interaction and hydrogen bonding were the predominant intermolecular forces between quercetin and product S.

  6. Endocrine disrupting activities of the flavonoid nutraceuticals luteolin and quercetin

    PubMed Central

    Nordeen, Steven K.; Bona, Betty J.; Jones, David N.; Lambert, James R.; Jackson, Twila A.

    2013-01-01

    Dietary plant flavonoids have been proposed to contribute to cancer prevention, neuroprotection, and cardiovascular health through their anti-oxidant, anti-inflammatory, pro-apoptotic, and antiproliferative activities. As a consequence, flavonoid supplements are aggressively marketed by the nutraceutical industry for many purposes, including pediatric applications, despite inadequate understanding of their value and drawbacks. We show that two flavonoids, luteolin and quercetin, are promiscuous endocrine disruptors. These flavonoids display progesterone antagonist activity beneficial in a breast cancer model but deleterious in an endometrial cancer model. Concurrently, luteolin possesses potent estrogen agonist activity while quercetin is considerably less effective. These results highlight the promise and peril of flavonoid nutraceuticals and suggest caution in supplementation beyond levels attained in a healthy, plant-rich diet. PMID:23836117

  7. 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

  8. Biosynthesis of two quercetin O-diglycosides in Escherichia coli.

    PubMed

    An, Dae Gyun; Yang, So Mi; Kim, Bong Gyu; Ahn, Joong-Hoon

    2016-06-01

    Various flavonoid glycosides are found in nature, and their biological activities are as variable as their number. In some cases, the sugar moiety attached to the flavonoid modulates its biological activities. Flavonoid glycones are not easily synthesized chemically. Therefore, in this study, we attempted to synthesize quercetin 3-O-glucosyl (1→2) xyloside and quercetin 3-O-glucosyl (1→6) rhamnoside (also called rutin) using two uridine diphosphate-dependent glycosyltransferases (UGTs) in Escherichia coli. To synthesize quercetin 3-O-glucosyl (1→2) xyloside, sequential glycosylation was carried out by regulating the expression time of the two UGTs. AtUGT78D2 was subcloned into a vector controlled by a Tac promoter without a lacI operator, while AtUGT79B1 was subcloned into a vector controlled by a T7 promoter. UDP-xyloside was supplied by concomitantly expressing UDP-glucose dehydrogenase (ugd) and UDP-xyloside synthase (UXS) in the E. coli. Using these strategies, 65.0 mg/L of quercetin 3-O-glucosyl (1→2) xyloside was produced. For the synthesis of rutin, one UGT (BcGT1) was integrated into the E. coli chromosome and the other UGT (Fg2) was expressed in a plasmid along with RHM2 (rhamnose synthase gene 2). After optimization of the initial cell concentration and incubation temperature, 119.8 mg/L of rutin was produced. The strategies used in this study thus show promise for the synthesis of flavonoid diglucosides in E. coli. PMID:26931782

  9. 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

  10. 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

  11. 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

  12. Antagonism of quercetin against tremor induced by unilateral striatal lesion of 6-OHDA in rats.

    PubMed

    Mu, Xin; Yuan, Xia; Du, Li-Da; He, Guo-Rong; Du, Guan-Hua

    2016-01-01

    Quercetin, a flavonoid present in many plants, is reported to be effective in models of neurodegenerative diseases. The aim of the present study was to evaluate the anti-tremor effects of quercetin in 6-hydroxydopamine (6-OHDA)-induced rat model of Parkinson's disease. In rats, quercetin had no effect on apomorphine-induced rotations, but it could significantly attenuate muscle tremor of 6-OHDA lesioned rats. Interestingly, quercetin could decrease the burst frequency in a dose- and time-dependent manner. These results suggest that quercetin may have a protective effect on models to mimic muscle tremors of Parkinson's disease. This effect of quercetin may be associated with serotonergic system, but further study is needed. PMID:26217978

  13. 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

  14. Different profiles of quercetin metabolites in rat plasma: comparison of two administration methods.

    PubMed

    Kawai, Yoshichika; Saito, Satomi; Nishikawa, Tomomi; Ishisaka, Akari; Murota, Kaeko; Terao, Junji

    2009-03-23

    The bioavailability of polyphenols in human and rodents has been discussed regarding their biological activity. We found different metabolite profiles of quercetin in rat plasma between two administration procedures. A single intragastric administration (50 mg/kg) resulted in the appearance of a variety of metabolites in the plasma, whereas only a major fraction was detected by free access (1% quercetin). The methylated/non-methylated metabolites ratio was much higher in the free access group. Mass spectrometric analyses showed that the fraction from free access contained highly conjugated quercetin metabolites such as sulfo-glucuronides of quercetin and methylquercetin. The metabolite profile of human plasma after an intake of onion was similar to that with intragastric administration in rats. In vitro oxidation of human low-density lipoprotein showed that methylation of the catechol moiety of quercetin significantly attenuated the antioxidative activity. These results might provide information about the bioavailability of quercetin when conducting animal experiments. PMID:19270373

  15. Quercetin from shallots (Allium cepa L. var. aggregatum) is more bioavailable than its glucosides.

    PubMed

    Wiczkowski, Wieslaw; Romaszko, Jerzy; Bucinski, Adam; Szawara-Nowak, Dorota; Honke, Joanna; Zielinski, Henryk; Piskula, Mariusz K

    2008-05-01

    The lipophilic character of quercetin suggests that it can cross enterocyte membranes via simple diffusion. Therefore, it should be more bioavailable than its glucosides, which require preliminary hydrolysis or active transport for absorption. However, the published human studies show that quercetin is less bioavailable than its glucosides. Assuming that low bioavailability of quercetin aglycone provided to humans as a pure substance is the result of its low solubility in the digestive tract, we studied its bioavailability from dietary sources in which quercetin was dispersed in the food matrix. In a randomized crossover study, 9 volunteers took a single dose of either shallot flesh (99.2% quercetin glucosides and 0.8% quercetin aglycone) or dry shallot skin (83.3% quercetin aglycone and 16.7% quercetin glucosides), providing 1.4 mg quercetin per kg of body weight. Blood samples were collected before and after consumption of shallot preparations. Plasma quercetin was measured on HPLC with electrochemical detection after plasma enzymatic treatment. The maximum plasma quercetin concentration of 1.02 +/- 0.13 micromol/L was reached at 2.33 +/- 0.50 h after shallot flesh consumption compared with 3.95 +/- 0.62 micromol/L at 2.78 +/- 0.15 h after dry skin consumption. The area under the concentration-time curve after dry skin consumption was 47.23 +/- 7.53 micromol x h(-1) x L(-1) and was significantly higher than that after shallot flesh intake (22.23 +/- 2.32 micromol x h(-1) x L(-1)). When provided along with dietary sources, quercetin aglycone is more bioavailable than its glucosides in humans. Results point to the food matrix as a key factor. PMID:18424596

  16. Effects of Functional Groups and Sugar Composition of Quercetin Derivatives on Their Radical Scavenging Properties.

    PubMed

    Kato, Komei; Ninomiya, Masayuki; Tanaka, Kaori; Koketsu, Mamoru

    2016-07-22

    Quercetin derivatives are widespread in the plant kingdom and exhibit various biological actions. The aim of this study was to investigate the structure-activity relationships of quercetin derivatives, with a focus on the influence of functional groups and sugar composition on their antioxidant capacity. A series of quercetin derivatives were therefore prepared and assessed for their DPPH radical scavenging properties. Isoquercetin O-gallates were more potent radical scavengers than quercetin. The systematic analysis highlights the importance of the distribution of hydroxy substituents in isoquercetin O-gallates to their potency. PMID:27314621

  17. Synergistic Effect of Functionalized Nickel Nanoparticles and Quercetin on Inhibition of the SMMC-7721 Cells Proliferation

    NASA Astrophysics Data System (ADS)

    Guo, Dadong; Wu, Chunhui; Li, Jingyuan; Guo, Airong; Li, Qingning; Jiang, Hui; Chen, Baoan; Wang, Xuemei

    2009-12-01

    The effect of functionalized nickel (Ni) nanoparticles capped with positively charged tetraheptylammonium on cellular uptake of drug quercetin into hepatocellular carcinoma cells (SMMC-7721) has been explored in this study via microscopy and electrochemical characterization as well as MTT assay. Meanwhile, the influence of Ni nanoparticles and/or quercetin on cell proliferation has been further evaluated by the real-time cell electronic sensing (RT-CES) study. Our observations indicate that Ni nanoparticles could efficiently improve the permeability of cancer cell membrane, and remarkably enhance the accumulation of quercetin in SMMC-7721 cells, suggesting that Ni nanoparticles and quercetin would facilitate the synergistic effect on inhibiting proliferation of cancer cells.

  18. A new acylated quercetin glycoside from the leaves of Stevia rebaudiana Bertoni.

    PubMed

    Li, Jun; Jiang, Hua; Shi, Renbing

    2009-01-01

    A new acylated quercetin glycoside quercetin-3-O-(4'''-O-trans-caffeoyl)-alpha-L-rhamnopyranosyl-(1-->6)-beta-D-galacopyranoside (1), along with luteolin (2), quercetin (3), luteolin-7-O-beta-D-glucoside (4), apigenin-7-O-beta-D-glucoside (5), quercitrin (6), quercetin-3-O-beta-D-arabinoside (7) and 4,5-di-O-caffeoyl quinic acid (8) have been isolated from the leaves of Stevia rebaudiana Bertoni. The structures of these compounds were determined by spectroscopic methods (1H- and 13C-NMR, IR and MS) and by 2D-NMR experiments. PMID:19809909

  19. Fluorescence enhancement of quercetin complexes by silver nanoparticles and its analytical application

    NASA Astrophysics Data System (ADS)

    Liu, Ping; Zhao, Liangliang; Wu, Xia; Huang, Fei; Wang, Minqin; Liu, Xiaodan

    2014-03-01

    It is found that the plasmon effect of silver nanoparticles (AgNPs) helps to enhance the fluorescence intensity of the quercetin (Qu) and nucleic acids system. Qu exhibited strong fluorescence enhancement when it bound to nucleic acids in the presence of AgNPs. Based on this, a sensitive method for the determination of nucleic acids was developed. The detection limits for the nucleic acids (S/N = 3) were reduced to the ng mL-1 level. The interaction mechanism of the AgNPs-fish sperm DNA (fsDNA)-Qu system was also investigated in this paper. This complex system of Qu and AgNPs was also successfully used for the detection of nucleic acids in agarose gel electrophoresis analysis. Preliminary results indicated that AgNPs also helped to improve sensitivity in the fluorescence image analysis of Qu combined with cellular contents in Arabidopsis thaliana protoplasts.

  20. Identification of brain-targeted bioactive dietary quercetin-3-O-glucuronide as a novel intervention for Alzheimer's disease

    PubMed Central

    Ho, Lap; Ferruzzi, Mario G.; Janle, Elsa M.; Wang, Jun; Gong, Bing; Chen, Tzu-Ying; Lobo, Jessica; Cooper, Bruce; Wu, Qing Li; Talcott, Stephen T.; Percival, Susan S.; Simon, James E.; Pasinetti, Giulio Maria

    2013-01-01

    Epidemiological and preclinical studies indicate that polyphenol intake from moderate consumption of red wines may lower the relative risk for developing Alzheimer's disease (AD) dementia. There is limited information regarding the specific biological activities and cellular and molecular mechanisms by which wine polyphenolic components might modulate AD. We assessed accumulations of polyphenols in the rat brain following oral dosage with a Cabernet Sauvignon red wine and tested brain-targeted polyphenols for potential beneficial AD disease-modifying activities. We identified accumulations of select polyphenolic metabolites in the brain. We demonstrated that, in comparison to vehicle-control treatment, one of the brain-targeted polyphenol metabolites, quercetin-3-O-glucuronide, significantly reduced the generation of β-amyloid (Aβ) peptides by primary neuron cultures generated from the Tg2576 AD mouse model. Another brain-targeted metabolite, malvidin-3-O-glucoside, had no detectable effect on Aβ generation. Moreover, in an in vitro analysis using the photo-induced cross-linking of unmodified proteins (PICUP) technique, we found that quercetin-3-O-glucuronide is also capable of interfering with the initial protein-protein interaction of Aβ1–40 and Aβ1–42 that is necessary for the formation of neurotoxic oligomeric Aβ species. Lastly, we found that quercetin-3-O-glucuronide treatment, compared to vehicle-control treatment, significantly improved AD-type deficits in hippocampal formation basal synaptic transmission and long-term potentiation, possibly through mechanisms involving the activation of the c-Jun N-terminal kinases and the mitogen-activated protein kinase signaling pathways. Brain-targeted quercetin-3-O-glucuronide may simultaneously modulate multiple independent AD disease-modifying mechanisms and, as such, may contribute to the benefits of dietary supplementation with red wines as an effective intervention for AD.—Ho, L., Ferruzzi, M. G

  1. 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

  2. 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

  3. Quercetin, kaempferol, myricetin, and fatty acid content among several Hibiscus sabdariffa accession calyces based on maturity in a greenhouse

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Flavonols including quercetin, kaempferol, myricetin, and fatty acids in plants have many useful health attributes including antioxidants, cholesterol lowering, and cancer prevention. Six accessions of roselle, Hibiscus sabdariffa calyces were evaluated for quercetin, kaempferol, and myricetin conte...

  4. Anthocyanin indexes, quercetin, kaempferol, and myricetin concentration in leaves and fruit of Abutilon theophrasti Medik. genetic resources

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Anthocyanin indexes, quercetin, kaempferol, and myricetin may provide industry with potential new medicines or nutraceuticals. Velvetleaf (Abutilon theophrasti Medik) leaves from 42 accessions were analyzed for anthocyanin indexes while both leaves and fruit were used for quercetin, kaempferol, and ...

  5. Incorporation of quercetin in lipid microparticles: effect on photo- and chemical-stability.

    PubMed

    Scalia, Santo; Mezzena, Matteo

    2009-01-15

    Lipid microparticles loaded with the flavonoid, quercetin were developed in order to enhance its stability in topical formulations. The microparticles were produced using tristearin as the lipid material and phosphatidylcholine as the emulsifier. The obtained lipoparticles were characterized by release studies, scanning electron microscopy and powder X-ray diffractometry. The quercetin loading was 12.1% (w/w). Free or microencapsulated quercetin was introduced in a model cream formulation (oil-in-water emulsion) and irradiated with a solar simulator. The extent of photodegradation was measured by high-performance liquid chromatography. The light-induced decomposition of quercetin in the cream vehicle was markedly decreased by incorporation into the lipid microparticles (the extent of degradation was 23.1+/-3.6% for non-encapsulated quercetin compared to 11.9+/-2.5% for the quercetin-loaded microparticles) and this photostabilization effect was maintained over time. Moreover, the chemical instability of quercetin, during 3-month storage of the formulations at room temperature and in the dark, was almost completely suppressed by the lipid microparticle system. Therefore incorporation of quercetin in lipoparticles represents an effective strategy to enhance its stability in dermatological products. PMID:19042102

  6. Preventive effect of dietary quercetin on disuse muscle atrophy by targeting mitochondria in denervated mice.

    PubMed

    Mukai, Rie; Matsui, Naoko; Fujikura, Yutaka; Matsumoto, Norifumi; Hou, De-Xing; Kanzaki, Noriyuki; Shibata, Hiroshi; Horikawa, Manabu; Iwasa, Keiko; Hirasaka, Katsuya; Nikawa, Takeshi; Terao, Junji

    2016-05-01

    Quercetin is a major dietary flavonoid in fruits and vegetables. We aimed to clarify the preventive effect of dietary quercetin on disuse muscle atrophy and the underlying mechanisms. We established a mouse denervation model by cutting the sciatic nerve in the right leg (SNX surgery) to lack of mobilization in hind-limb. Preintake of a quercetin-mixed diet for 14days before SNX surgery prevented loss of muscle mass and atrophy of muscle fibers in the gastrocnemius muscle (GM). Phosphorylation of Akt, a key phosphorylation pathway of suppression of protein degradation, was activated in the quercetin-mixed diet group with and without SNX surgery. Intake of a quercetin-mixed diet suppressed the generation of hydrogen peroxide originating from mitochondria and elevated mitochondrial peroxisome proliferator-activated receptor-γ coactivator 1α mRNA expression as well as NADH dehydrogenase 4 expression in the GM with SNX surgery. Quercetin and its conjugated metabolites reduced hydrogen peroxide production in the mitochondrial fraction obtained from atrophied muscle. In C2C12 myotubes, quercetin reached the mitochondrial fraction. These findings suggest that dietary quercetin can prevent disuse muscle atrophy by targeting mitochondria in skeletal muscle tissue through protecting mitochondria from decreased biogenesis and reducing mitochondrial hydrogen peroxide release, which can be related to decreased hydrogen peroxide production and/or improvements on antioxidant capacity of mitochondria. PMID:27133425

  7. 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

  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. 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.

  10. 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

  11. Effects of quercetin on pharmacokinetics of cefprozil in Chinese-Han male volunteers.

    PubMed

    Jia, Fei-Fei; Tan, Zhi-Rong; McLeod, Howard L; Chen, Yao; Ou-Yang, Dong-Sheng; Zhou, Hong-Hao

    2016-10-01

    1. The primary objective of this study was to evaluate the effects of quercetin on the pharmacokinetics of cefprozil. The secondary objective was to evaluate the safety of the combined use of cefprozil and quercetin. 2. An open-label, two-period, crossover phase I trial among 24 Han Chinese male subjects was conducted. Participants were given 500 mg of quercetin orally once daily for 15 d followed by single dose of cefprozil (500 mg) on day 15. Serum concentrations of cefprozil were then measured in all participants on day 15. A 15-d washout period was then assigned after which a 500 mg dose of cefprozil was administered and measured in the serum on day 36. 3. All subjects completed the trial, and no serious adverse events were reported. We measured mean serum concentrations of cefprozil in the presence and absence of quercetin in all participants. The maximum serum concentration of cefprozil in the presence of quercetin was 8.18 ug/ml (95% CI: 7.55-8.81) versus a maximum cefprozil concentration of 8.35 ug/ml (95% CI: 7.51-9.19) in the absence of quercetin. We conclude that the concurrent use of quercetin has no substantial effect on serum concentrations of orally administered cefprozil. 4. Co-administration of quercetin showed no statistically significant effects on the pharmacokinetics of cefprozil in healthy Chinese subjects. PMID:26928207

  12. Genetic expression profile analysis of the temporal inhibition of quercetin and naringenin on Lactobacillus rhamnosus GG

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The plant polyphenols, quercetin and naringenin, are considered healthy dietary compounds; however, little is known of their effects on the probiotic Lactobacillus rhamnosus GG (LGG). In this study, it was discovered that both quercetin and naringenin produced temporary inhibition of LGG growth, par...

  13. 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

  14. Microsomal quercetin glucuronidation in rat small intestine depends on age and segment

    Technology Transfer Automated Retrieval System (TEKTRAN)

    UDP-glucuronosyltransferase (UGT) activity toward the flavonoid quercetin and UGT protein were characterized in 3 equidistant small intestine (SI) segments from 4, 12, 18, and 28 mo male F344 rats, n=8/age using villin to control for enterocyte content. SI microsomal intrinsic clearance of quercetin...

  15. Antioxidant property of quercetin-Cr(III) complex: The role of Cr(III) ion

    NASA Astrophysics Data System (ADS)

    Chen, Weijun; Sun, Shaofang; cao, Wei; Liang, Yan; Song, Jirong

    2009-01-01

    Flavonoid-metal complex is reported to exhibit a higher antioxidant activity than parent flavonoid. In this paper, experimental and theoretical methods are applied to study the antioxidant properties of quercetin and quercetin-Cr(III) complex, to find out the antioxidant activity variation and the role of Cr(III) ion on the antioxidant activity of the complex. Bond dissociation energy (BDE) and ionization potential (IP) of quercetin and the complex are calculated at the B3LYP/6-311++G(2d,2p)//B3LYP/LANL2DZ level. The experimental results show that the complex has a higher DPPH radical scavenging activity than quercetin. The calculated results show that the complex displays lower BDE and IP than quercetin. The IP of the complex declines obviously, indicating that the Cr (III) ion has more impact on the electron donating ability than on the hydrogen atom transferring ability of the complex.

  16. The effect of quercetin dietary supplementation on meat oxidation processes and texture of fattening lambs.

    PubMed

    Andrés, S; Huerga, L; Mateo, J; Tejido, M L; Bodas, R; Morán, L; Prieto, N; Rotolo, L; Giráldez, F J

    2014-02-01

    Thirty two lambs were fed a total mixed ration (TMR) formulated either with palm oil (CTRL; 34 g palm oil kg(-1) TMR) or whole flaxseed (+FS, 85 g flaxseed kg(-1) TMR) alone or enriched with quercetin (+QCT, 34 g palm oil plus 2 g quercetin kg(-1) TMR; +FS+QCT, 85 g flaxseed plus 2 g quercetin kg(-1) TMR). Dietary flaxseed did not affect, in a significant manner, the lipid peroxidation of meat samples. Quercetin treatment reduced oxysterol content (P<0.05) after 7 days of refrigerated storage of fresh meat, but did not affect significantly (P>0.05) the level of lipid-derived volatiles in the headspace of the light-exposed stored cooked meat. Sensory evaluation showed flaxseed as being responsible for a negative effect on meat flavour, probably associated with a modification of the fatty acid profile whereas, unexpectedly, quercetin seemed to worsen meat tenderisation. PMID:24200574

  17. 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

  18. 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

  19. 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

  20. Evaluation of polyamidoamine dendrimers as potential carriers for quercetin, a versatile flavonoid.

    PubMed

    Madaan, Kanika; Lather, Viney; Pandita, Deepti

    2016-01-01

    The aim of the present research work was to investigate the potential of polyamidoamine (PAMAM) dendrimers as oral drug delivery carriers for quercetin, a Biopharmaceutical Classification System (BCS) class II molecule. The aqueous solubility of quercetin was investigated in different generations of dendrimers, i.e. G0, G1, G2 and G3, with varying concentrations (0.1, 0.5, 1, 2 and 4 µM). Then, it was successfully incorporated in PAMAM dendrimers and they were characterized for incorporation efficacy, nature of nanoformulations, size, size distribution, surface morphology and stability. In vitro release characteristics of quercetin from all quercetin-PAMAM complexes were studied at 37 °C in phosphate buffer saline (PBS; pH 7.4). Furthermore, the efficacy of quercetin-loaded PAMAM dendrimer was assessed by pharmacodynamic experiment, namely, a carrageenan-induced paw edema model to evaluate the acute activity of this nanocarrier in response to inflammation. It was observed that both generation and the respective concentrations of PAMAM dendrimers showed potential positive effects on solubility enhancement of quercetin. All the quercetin-PAMAM complexes were found to be in nanometeric range (<100 nm) with narrow polydispersity index. In vitro study revealed a biphasic release pattern of quercetin which was characterized by an initial faster release followed by sustained release phase and pharmacodynamic study provided the preliminary proof of concept about the potential of quercetin-PAMAM complexes. The study concludes that the dendrimer-based drug delivery system for quercetin has enormous potential to resolve the drug delivery issues associated with it. PMID:24845475

  1. 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

  2. Characterisation of metabolites of the putative cancer chemopreventive agent quercetin and their effect on cyclo-oxygenase activity

    PubMed Central

    Jones, D J L; Lamb, J H; Verschoyle, R D; Howells, L M; Butterworth, M; Lim, C K; Ferry, D; Farmer, P B; Gescher, A J

    2004-01-01

    Quercetin (3,5,7,3′,4′-pentahydroxyflavone) is a flavone with putative ability to prevent cancer and cardiovascular diseases. Its metabolism was evaluated in rats and human. Rats received quercetin via the intravenous (i.v.) route and metabolites were isolated from the plasma, urine and bile. Analysis was by high-performance liquid chromatography and confirmation of species identity was achieved by mass spectrometry. Quercetin and isorhamnetin, the 3′-O-methyl analogue, were found in both the plasma and urine. In addition, several polar peaks were characterised as sulphated and glucuronidated conjugates of quercetin and isorhamnetin. Extension of the metabolism studies to a cancer patient who had received quercetin as an i.v. bolus showed that (Quercetin removed) isorhamnetin and quercetin 3′-O-sulphate were major plasma metabolites. As a catechol, quercetin can potentially be converted to a quinone and subsequently conjugated with glutathione (GSH). Oxidation of quercetin with mushroom tyrosinase in the presence of GSH furnished GSH conjugates of quercetin, two mono- and one bis-substituted conjugates. However, these species were not found in biomatrices in rats treated with quercetin. As cyclo-oxygenase-2 (COX-2) expression is mechanistically linked to carcinogenesis, we examined whether quercetin and its metabolites can inhibit COX-2 in a human colorectal cancer cell line (HCA-7). Isorhamnetin and its 4′-isomer tamarixetin were potent inhibitors, reflected in a 90% decrease in prostaglandin E-2 (PGE-2) levels, a marker of COX-2 activity. Quercetin was less effective, with a 50% decline. Quercetin 3- and 7-O-sulphate had no effect on PGE-2. The results indicate that quercetin may exert its pharmacological effects, at least in part, via its metabolites. PMID:15292928

  3. 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

  4. Release of quercetin from micellar nanoparticles with saturated and unsaturated core forming polyesters--a combined computational and experimental study.

    PubMed

    Hassanzadeh, Salman; Khoee, Sepideh; Beheshti, Abolghasem; Hakkarainen, Minna

    2015-01-01

    Computational and experimental studies were combined to obtain new insight into the widely reported anomalous release mechanism of hydrophobic drug (quercetin) from polymeric micellar nanoparticles. Saturated and unsaturated amphiphilic triblock copolymers from monomethoxy polyethylene glycol (mPEG), poly(butylene adipate) (PBA) and poly(cis-2-butene adipate) (PCBA) (mPEG-PBA-mPEG and mPEG-PCBA-mPEG) were utilized as model polymers to specify the contribution of polymer-micelle degradation and polymer-drug interactions on the observed differences in the release rates by applicable computational investigation and experimental evaluations. Monitoring the size of the micelles through the releasing process together with hydrolytic degradation studies of the core forming polymers proved that the contribution of polymer hydrolysis and micelle degradation on the observed differences in the release rates during the release time window was minimal. The compatibility between quercetin and the core forming polymer is another factor influencing the drug encapsulation and the relative release rate and it was therefore investigated theoretically (using density functional theory (DFT) at B3LYP/6-311(++)G level of theory) and experimentally (FT-IR imaging). The drug-polymer interactions in the core were shown to be much more important than the polymer and/or micelle swelling-dissociation-degradation processes under the studied conditions. PMID:25492006

  5. Dietary quercetin exacerbates the development of estrogen-induced breast tumors in female ACI rats

    SciTech Connect

    Singh, Bhupendra; Mense, Sarah M.; Bhat, Nimee K.; Putty, Sandeep; Guthiel, William A.; Remotti, Fabrizio; Bhat, Hari K.

    2010-09-01

    Phytoestrogens are plant compounds that structurally mimic the endogenous estrogen 17{beta}-estradiol (E{sub 2}). Despite intense investigation, the net effect of phytoestrogen exposure on the breast remains unclear. The objective of the current study was to examine the effects of quercetin on E{sub 2}-induced breast cancer in vivo. Female ACI rats were given quercetin (2.5 g/kg food) for 8 months. Animals were monitored weekly for palpable tumors, and at the end of the experiment, rats were euthanized, breast tumor and different tissues excised so that they could be examined for histopathologic changes, estrogen metabolic activity and oxidant stress. Quercetin alone did not induce mammary tumors in female ACI rats. However, in rats implanted with E{sub 2} pellets, co-exposure to quercetin did not protect rats from E{sub 2}-induced breast tumor development with 100% of the animals developing breast tumors within 8 months of treatment. No changes in serum quercetin levels were observed in quercetin and quercetin + E{sub 2}-treated groups at the end of the experiment. Tumor latency was significantly decreased among rats from the quercetin + E{sub 2} group relative to those in the E{sub 2} group. Catechol-O-methyltransferase (COMT) activity was significantly downregulated in quercetin-exposed mammary tissue. Analysis of 8-isoprostane F{sub 2{alpha}} (8-iso-PGF{sub 2{alpha}}) levels as a marker of oxidant stress showed that quercetin did not decrease E{sub 2}-induced oxidant stress. These results indicate that quercetin (2.5 g/kg food) does not confer protection against breast cancer, does not inhibit E{sub 2}-induced oxidant stress and may exacerbate breast carcinogenesis in E{sub 2}-treated ACI rats. Inhibition of COMT activity by quercetin may expose breast cells chronically to E{sub 2} and catechol estrogens. This would permit longer exposure times to the carcinogenic metabolites of E{sub 2} and chronic exposure to oxidant stress as a result of metabolic redox

  6. Theoretical Study of the ESIPT Process for a New Natural Product Quercetin.

    PubMed

    Yang, Yunfan; Zhao, Jinfeng; Li, Yongqing

    2016-01-01

    The investigation of excited-state intramolecular proton transfer (ESIPT) has been carried out via the density functional theory (DFT) and the time-dependent density functional theory (TDDFT) method for natural product quercetin in dichloromethane (DCM) solvent. For distinguishing different types of intramolecular interaction, the reduced density gradient (RDG) function also has been used. In this study, we have clearly clarified the viewpoint that two kinds of tautomeric forms (K1, K2)originated from ESIPT processconsist inthe first electronic excited state (S1). The phenomenon of hydrogen bonding interaction strengtheninghas been proved by comparing the changes of infrared (IR) vibrational spectra and bond parameters of the hydrogen bonding groups in the ground state with that in the first excited state. The frontier molecular orbitals (MOs)provided visual electron density redistribution have further verified the hydrogen bond strengthening mechanism. It should be noted that the ESIPT process of the K2 form is easier to occur than that of the K1 form via observing the potential energy profiles. Furthermore, the RDG isosurfaces has indicated that hydrogen bonding interaction of the K2 form is stronger than that of the K1 formin the S1 state, which is also the reason why the ESIPT process of the K2 form is easier to occur. PMID:27574105

  7. Theoretical Study of the ESIPT Process for a New Natural Product Quercetin

    PubMed Central

    Yang, Yunfan; Zhao, Jinfeng; Li, Yongqing

    2016-01-01

    The investigation of excited-state intramolecular proton transfer (ESIPT) has been carried out via the density functional theory (DFT) and the time-dependent density functional theory (TDDFT) method for natural product quercetin in dichloromethane (DCM) solvent. For distinguishing different types of intramolecular interaction, the reduced density gradient (RDG) function also has been used. In this study, we have clearly clarified the viewpoint that two kinds of tautomeric forms (K1, K2)originated from ESIPT processconsist inthe first electronic excited state (S1). The phenomenon of hydrogen bonding interaction strengtheninghas been proved by comparing the changes of infrared (IR) vibrational spectra and bond parameters of the hydrogen bonding groups in the ground state with that in the first excited state. The frontier molecular orbitals (MOs)provided visual electron density redistribution have further verified the hydrogen bond strengthening mechanism. It should be noted that the ESIPT process of the K2 form is easier to occur than that of the K1 form via observing the potential energy profiles. Furthermore, the RDG isosurfaces has indicated that hydrogen bonding interaction of the K2 form is stronger than that of the K1 formin the S1 state, which is also the reason why the ESIPT process of the K2 form is easier to occur. PMID:27574105

  8. 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.

  9. Protective effects of onion-derived quercetin on glutamate-mediated hippocampal neuronal cell death

    PubMed Central

    Yang, Eun-Ju; Kim, Geum-Soog; Kim, Jeong Ah; Song, Kyung-Sik

    2013-01-01

    Background: Neurodegenerative diseases are characterized by progressive neuron degeneration in specific functional systems of the central or peripheral nervous system. This study investigated the protective effects of quercetin isolated from onion on neuronal cells and its protective mechanisms against glutamate-induced apoptosis in HT22 cells. Materials and Methods: HT22 cells were cultured to study the neuroprotective mechanism of quercetin against glutamate-mediated oxidative stress. The intracellular reactive oxygen species (ROS) level and mitochondrial membrane potential (ΔΨm) were measured. The protein expression of calpain, spectrin, Bcl-2, Bax, Bid, cytochrome c, and mitogen-activated protein kinases (MAPKs) was evaluated by Western blotting. Results: Quercetin had a protective effect by reducing both intracellular ROS overproduction and glutamate-mediated Ca2+ influx. These effects were due to the downregulation of several apoptosis-related biochemical markers. Calpain expression was reduced and spectrin cleavage was inhibited by quercetin in glutamate-exposed HT22 cells. Disruption of the mitochondrial membrane potential (ΔΨm), activation of the pro-apoptotic proteins Bid and Bax, and cytochrome c release in response to glutamate-induced oxidative stress were reduced. Quercetin also suppressed phosphorylation of MAPKs. Conclusion: This is the first report on the detailed mechanisms of the protective effect of quercetin on HT22 cells. Onion extract and quercetin may be useful for preventing or treating neurodegenerative disorders. PMID:24124281

  10. Quercetin-3-O-glucuronide induces ABCA1 expression by LXRα activation in murine macrophages

    SciTech Connect

    Ohara, Kazuaki; Wakabayashi, Hideyuki; Taniguchi, Yoshimasa; Shindo, Kazutoshi; Yajima, Hiroaki; Yoshida, Aruto

    2013-11-29

    Highlights: •The major circulating quercetin metabolite (Q3GA) activated LXRα. •Q3GA induced ABCA1 via LXRα activation in macrophages. •Nelumbo nucifera leaf extracts contained quercetin glycosides. •N. nucifera leaf extract feeding elevated HDLC in mice. -- Abstract: Reverse cholesterol transport (RCT) removes excess cholesterol from macrophages to prevent atherosclerosis. ATP-binding cassette, subfamily A, member 1 (ABCA1) is a crucial cholesterol transporter involved in RCT to produce high density lipoprotein-cholesterol (HDLC), and is transcriptionally regulated by liver X receptor alpha (LXRα), a nuclear receptor. Quercetin is a widely distributed flavonoid in edible plants which prevented atherosclerosis in an animal model. We found that quercetin-3-O-glucuronide (Q3GA), a major quercetin metabolite after absorption from the digestive tract, enhanced ABCA1 expression, in vitro, via LXRα in macrophages. In addition, leaf extracts of a traditional Asian edible plant, Nelumbo nucifera (NNE), which contained abundant amounts of quercetin glycosides, significantly elevated plasma HDLC in mice. We are the first to present experimental evidence that Q3GA induced ABCA1 in macrophages, and to provide an alternative explanation to previous studies on arteriosclerosis prevention by quercetin.

  11. 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

  12. The flavonoid quercetin modulates the hallmark capabilities of hamster buccal pouch tumors.

    PubMed

    Priyadarsini, Ramamurthi Vidya; Vinothini, Govindarajah; Murugan, Ramalingam Senthil; Manikandan, Palrasu; Nagini, Siddavaram

    2011-01-01

    Epidemiological studies have consistently demonstrated the protective effects of dietary phytochemicals against cancer risk. Quercetin, a ubiquitous dietary flavonoid, has attracted considerable attention owing to its potent antioxidant and antiproliferative activities. The present study was designed to investigate the chemopreventive as well as the therapeutic ability of quercetin to modulate the key hallmark capabilities of 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinomas. We analyzed the expression of markers associated with cell proliferation and survival (PCNA, p21, p53, cyclin D1, GST-P), apoptosis (Fas, Fas-L, Bcl-2 family proteins, cytochrome-C, Apaf-1, caspases, PARP, survivin, cFLIP, API1), invasion (MMPs, TIMP-2, RECK), angiogenesis (PlGF, VEGF, VEGF receptors, HIF-1α), as well as the epigenetic markers (HDAC-1, DNMT1) by immunohistochemical, Western blot, and RT-PCR analyses. Simultaneous administration of quercetin to DMBA-painted hamsters reduced tumor incidence and tumor burden, while posttreatment of quercetin resulted in a significant tumor growth delay. In addition, quercetin administration induced cell cycle arrest and apoptosis and blocked invasion and angiogenesis. We found a positive correlation between the inhibition of HDAC-1 and DNMT1 by quercetin and its anticancer properties. A dietary phytochemical such as quercetin that modulates a plethora of molecules offers promise as an ideal candidate for multitargeted cancer prevention and therapy. PMID:21294050

  13. Extraction of quercetin from Herba Lysimachiae by molecularly imprinted-matrix solid phase dispersion.

    PubMed

    Hong, Yansuo; Chen, Ligang

    2013-12-15

    A new kind of quercetin molecularly imprinted polymer (MIP) was synthesized and applied as a selective sorbent in matrix solid-phase dispersion (MSPD) for the extraction of quercetin in Herba Lysimachiae. The MIP was prepared by surface imprinting method using quercetin as template, methacrylic acid as functional monomer, trimethylolpropane trimethacrylate as crosslinker and methanol as porogen. The selectivity of quercetin MIP was evaluated according to their recognition to quercetin and a compound with similar molecular size (bergenin). Good binding for quercetin was observed in MIP adsorption experiment. The isothermal adsorption and dynamic adsorption experiments were also carried out in this study. The best quercetin extraction conditions were as follows: the ratio of MIP to sample was 1:1, the dispersion time was 10min, washing solvent was 2% aqueous methanol and elution solvent was acetic acid-methanol (2:98, v/v). The proposed method was compared with the method used in Chinese pharmacopeia. The similar extraction yield was obtained by the two methods. Moreover, this method is faster, simpler and can realize extraction and purification procedures in the same system. PMID:24184834

  14. Quercetin Influences Quorum Sensing in Food Borne Bacteria: In-Vitro and In-Silico Evidence

    PubMed Central

    Gopu, Venkadesaperumal; Meena, Chetan Kumar; Shetty, Prathapkumar Halady

    2015-01-01

    Quorum sensing (QS) plays a vital role in regulating the virulence factor of many food borne pathogens, which causes severe public health risk. Therefore, interrupting the QS signaling pathway may be an attractive strategy to combat microbial infections. In the current study QS inhibitory activity of quercetin and its anti-biofilm property was assessed against food-borne pathogens using a bio-sensor strain. In addition in-silico techniques like molecular docking and molecular dynamics simulation studies were applied to screen the quercetin’s potentiality as QS inhibitor. Quercetin (80μg/ml) showed the significant reduction in QS-dependent phenotypes like violacein production, biofilm formation, exopolysaccharide (EPS) production, motility and alginate production in a concentration-dependent manner. Synergistic activity of conventional antibiotics with quercetin enhanced the susceptibility of all tested pathogens. Furthermore, Molecular docking analysis revealed that quercetin binds more rigidly with LasR receptor protein than the signaling compound with docking score of -9.17Kcal/mol. Molecular dynamics simulation predicted that QS inhibitory activity of quercetin occurs through the conformational changes between the receptor and quercetin complex. Above findings suggest that quercetin can act as a competitive inhibitor for signaling compound towards LasR receptor pathway and can serve as a novel QS-based antibacterial/anti-biofilm drug to manage food-borne pathogens. PMID:26248208

  15. 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

  16. 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

  17. 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

  18. Effect of Quercetin on Hepatitis C Virus Life Cycle: From Viral to Host Targets.

    PubMed

    Rojas, Ángela; Del Campo, Jose A; Clement, Sophie; Lemasson, Matthieu; García-Valdecasas, Marta; Gil-Gómez, Antonio; Ranchal, Isidora; Bartosch, Birke; Bautista, Juan D; Rosenberg, Arielle R; Negro, Francesco; Romero-Gómez, Manuel

    2016-01-01

    Quercetin is a natural flavonoid, which has been shown to have anti hepatitis C virus (HCV) properties. However, the exact mechanisms whereby quercetin impacts the HCV life cycle are not fully understood. We assessed the effect of quercetin on different steps of the HCV life cycle in Huh-7.5 cells and primary human hepatocytes (PHH) infected with HCVcc. In both cell types, quercetin significantly decreased i) the viral genome replication; ii) the production of infectious HCV particles and iii) the specific infectivity of the newly produced viral particles (by 85% and 92%, Huh7.5 and PHH respectively). In addition, when applied directly on HCV particles, quercetin reduced their infectivity by 65%, suggesting that it affects the virion integrity. Interestingly, the HCV-induced up-regulation of diacylglycerol acyltransferase (DGAT) and the typical localization of the HCV core protein to the surface of lipid droplets, known to be mediated by DGAT, were both prevented by quercetin. In conclusion, quercetin appears to have direct and host-mediated antiviral effects against HCV. PMID:27546480

  19. Effect of Quercetin on Hepatitis C Virus Life Cycle: From Viral to Host Targets

    PubMed Central

    Rojas, Ángela; Del Campo, Jose A.; Clement, Sophie; Lemasson, Matthieu; García-Valdecasas, Marta; Gil-Gómez, Antonio; Ranchal, Isidora; Bartosch, Birke; Bautista, Juan D.; Rosenberg, Arielle R.; Negro, Francesco; Romero-Gómez, Manuel

    2016-01-01

    Quercetin is a natural flavonoid, which has been shown to have anti hepatitis C virus (HCV) properties. However, the exact mechanisms whereby quercetin impacts the HCV life cycle are not fully understood. We assessed the effect of quercetin on different steps of the HCV life cycle in Huh-7.5 cells and primary human hepatocytes (PHH) infected with HCVcc. In both cell types, quercetin significantly decreased i) the viral genome replication; ii) the production of infectious HCV particles and iii) the specific infectivity of the newly produced viral particles (by 85% and 92%, Huh7.5 and PHH respectively). In addition, when applied directly on HCV particles, quercetin reduced their infectivity by 65%, suggesting that it affects the virion integrity. Interestingly, the HCV-induced up-regulation of diacylglycerol acyltransferase (DGAT) and the typical localization of the HCV core protein to the surface of lipid droplets, known to be mediated by DGAT, were both prevented by quercetin. In conclusion, quercetin appears to have direct and host-mediated antiviral effects against HCV. PMID:27546480

  20. 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

  1. Quercetin, a potent suppressor of NF-κB and Smad activation in osteoblasts.

    PubMed

    Yamaguchi, Masayoshi; Weitzmann, M Neale

    2011-10-01

    Osteoclasts, the bone resorbing cells of the body, form when osteoclast precursors are exposed to the key osteoclastogenic cytokine receptor activator of NF-κB ligand (RANKL), a process requiring induction of NF-κB signaling. Quercetin is a ubiquitous plant-derived flavonoid with well documented anti-inflammatory properties, in part, a consequence of its capacity to downmodulate the NF-κB signal transduction pathway. Consistent with this mechanism of action quercetin is reported to suppress osteoclastogenesis in vitro and prevent bone loss in ovariectomized mice in vivo. By contrast, the effect of quercetin on osteoblasts, the cells responsible for bone formation, is contradictory with conflicting reports of inhibition as well as stimulation. Given our previous reports that NF-κB antagonists promote osteoblast differentiation and activity, we compared the effects of quercetin on osteoclast and osteoblast differentiation and on NF-κB signal transduction in vitro. As expected, quercetin potently suppressed osteoclastogenesis and NF-κB activation induced by RANKL in osteoclast precursors. However, the same doses of quercetin had no effect on osteoblast mineralization, and failed to significantly alleviate the inhibitory effect of NF-κB-induced by TNFα, even though quercetin potently suppressed NF-κB activation in these cells. This apparent contradiction was explained by the fact that addition to its anti-NF-κB activity, quercetin also potently antagonized both TGFβ and BMP-2-induced Smad activation in osteoblast precursors. Taken together our data suggest that multiple competing actions of quercetin mediate both stimulatory and inhibitory actions on osteoblasts with the final physiological effect likely a function of the net balance between these stimulatory and inhibitory effects. PMID:21769418

  2. Dietary quercetin inhibits bone loss without effect on the uterus in ovariectomized mice.

    PubMed

    Tsuji, Mitsuyoshi; Yamamoto, Hironori; Sato, Tadatoshi; Mizuha, Yoko; Kawai, Yoshichika; Taketani, Yutaka; Kato, Shigeaki; Terao, Junji; Inakuma, Takahiro; Takeda, Eiji

    2009-01-01

    Quercetin is a major dietary flavonoid found in onions and other vegetables, and potentially has beneficial effects on disease prevention. In the present study, we demonstrate for the first time the effects of dietary quercetin on bone loss and uterine weight loss by ovariectomy in vivo. Female mice were ovariectomized (OVX) and were randomly allocated to 3 groups: a control diet or a diet with 0.25% (LQ) or 2.5% quercetin (HQ). After 4 weeks, dietary quercetin had no effects on uterine weight in OVX mice, but bone mineral density of the lumbar spine L4 and femur measured by peripheral quantitative computed tomography (pQCT) was higher in both the sham and the HQ groups than in the OVX group. Histomorphometric analysis showed that the HQ group restored bone volume (BV/TV) completely in distal femoral cancellous bone, but did not reduce the osteoclast surface area and osteoclast number when compared with the OVX group. In in-vitro experiments using mouse monocyte/macrophage cell line RAW264.7 cells, however, quercetin and its conjugate, quercetin-3-O-beta-D: -glucuronide dose-dependently inhibited the receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclast differentiation, and the RANKL-stimulated expression of osteoclast related genes was also inhibited by quercetin. The luciferase reporter assay showed that quercetin did not appear to have estrogenic activity through estrogen receptors. These results suggest that dietary quercetin inhibits bone loss without effect on the uterus in OVX mice and does not act as a potent inhibitor of osteoclastogenesis or as a selective estrogen receptor modulator in vivo. PMID:19495926

  3. 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

  4. Antiatherogenic Roles of Dietary Flavonoids Chrysin, Quercetin, and Luteolin.

    PubMed

    Basu, Anandita; Das, Anindhya S; Majumder, Munmi; Mukhopadhyay, Rupak

    2016-07-01

    Cardiovascular diseases (CVDs) are the commonest cause of global mortality and morbidity. Atherosclerosis, the fundamental pathological manifestation of CVDs, is a complex process and is poorly managed both in terms of preventive and therapeutic intervention. Aberrant lipid metabolism and chronic inflammation play critical roles in the development of atherosclerosis. These processes can be targeted for effective management of the disease. Although managing lipid metabolism is in the forefront of current therapeutic approaches, controlling inflammation may also prove to be crucial for an efficient treatment regimen of the disease. Flavonoids, the plant-derived polyphenols, are known for their antiinflammatory properties. This review discusses the possible antiatherogenic role of 3 flavonoids, namely, chrysin, quercetin, and luteolin primarily known for their antiinflammatory properties. PMID:27385185

  5. Ameliorative Effect of Quercetin on Neurochemical and Behavioral Deficits in Rotenone Rat Model of Parkinson's Disease: Modulating Autophagy (Quercetin on Experimental Parkinson's Disease).

    PubMed

    El-Horany, Hemat E; El-Latif, Rania N Abd; ElBatsh, Maha M; Emam, Marwa N

    2016-07-01

    Autophagy is necessary for neuronal homeostasis and its dysfunction has been implicated in Parkinson's disease (PD) as it can exacerbate endoplasmic reticulum (ER) stress and ER stress-induced apoptosis. Quercetin is a flavonoid known for its neuroprotective and antioxidant effects. The present study investigated the protective, autophagy-modulating effects of quercetin in the rotenone rat model of PD. Rotenone was intraperitoneally injected at dose of 2 ml/kg/day for 4 weeks. Simultaneous intraperitoneal injection of quercetin was given at a dose of 50 mg/kg/day also for 4 weeks. Neurobehavioral changes were studied. Oxidative/antioxidant status, C/EBP homologous protein (CHOP), Beclin-1, and dopamine levels were assessed. DNA fragmentation and histopathological changes were evaluated. This research work revealed that quercetin significantly attenuated rotenone-induced behavioral impairment, augmented autophagy, ameliorated ER stress- induced apoptosis with attenuated oxidative stress. From the current study, quercetin can act as an autophagy enhancer in PD rat model and modulates the microenvironment that leads to neuronal death. PMID:27252111

  6. Role of quercetin on Caco-2 cells against cytotoxic effects of alternariol and alternariol monomethyl ether.

    PubMed

    Fernández-Blanco, Celia; Font, Guillermina; Ruiz, Maria-Jose

    2016-03-01

    Molds of the genus Alternaria have been reported as contaminants of a variety of food and feed. Alternaria toxins such as alternariol (AOH) and its naturally occurring monomethyl ether (AME) produce cytotoxicity and oxidative stress in cell cultures. On the other hand, it has been proved that natural polyphenols have antioxidant effect. Quercetin (Quer) is a polyphenol present in berries and other commodities which exhibits these effects. The aims were to evaluate the cytotoxicity of AOH, AME and the binary combination of them, and the cytoprotective effect of Quer exposed simultaneously with AOH, AME and the mycotoxin mixture in human adenocarcinoma (Caco-2) cells. The cytotoxicity and the cytoprotective effect were determined by the MTT test after 24 and 48 h of exposure and interactions were evaluated with the isobologram analysis method. Cell viability decreased after 48 h of AOH and AME exposures, being the binary combination more cytotoxic, causing a synergism effect. No cytoprotective effect of Quer against AOH and AME was observed when they were exposed simultaneously in Caco-2 cells. The cytoprotective effect of Quer against mycotoxins (AOH, AME or other different which could present higher cytotoxic effect) depends on the concentration, the presence and the interaction between the compounds in food. PMID:26802676

  7. Dimerization of human uridine diphosphate glucuronosyltransferase allozymes 1A1 and 1A9 alters their quercetin glucuronidation activities.

    PubMed

    Liu, Yan-Qing; Yuan, Ling-Min; Gao, Zhang-Zhao; Xiao, Yong-Sheng; Sun, Hong-Ying; Yu, Lu-Shan; Zeng, Su

    2016-01-01

    Uridine diphosphate glucuronosyltransferase 1A (UGT1A) is a major phase II drug-metabolism enzyme superfamily involved in the glucuronidation of endobiotics and xenobiotics in humans. Many polymorphisms in UGT1A genes are reported to inhibit or decrease UGT1A activity. In this study, two UGT1A1 allozymes, UGT1A1 wild-type and a splice mutant, as well as UGT1A9 wild-type and its three UGT1A9 allozymes, UGT1A9*2(C3Y), UGT1A9*3(M33T), and UGT1A9*5(D256N) were single- or double-expressed in a Bac-to-Bac expression system. Dimerization of UGT1A1 or UGT1A9 allozymes was observed via fluorescence resonance energy transfer (FRET) and co-immunoprecipitation analysis. SNPs of UGT1A altered the ability of protein-protein interaction, resulting in differential FRET efficiencies and donor-acceptor r distances. Dimerization changed the chemical regioselectivity, substrate-binding affinity, and enzymatic activity of UGT1A1 and UGT1A9 in glucuronidation of quercetin. These findings provide molecular insights into the consequences of homozygous and heterozygous UGT1A1 and UGT1A9 allozymes expression on quercetin glucuronidation. PMID:27025983

  8. Dimerization of human uridine diphosphate glucuronosyltransferase allozymes 1A1 and 1A9 alters their quercetin glucuronidation activities

    PubMed Central

    Liu, Yan-Qing; Yuan, Ling-Min; Gao, Zhang-Zhao; Xiao, Yong-Sheng; Sun, Hong-Ying; Yu, Lu-Shan; Zeng, Su

    2016-01-01

    Uridine diphosphate glucuronosyltransferase 1A (UGT1A) is a major phase II drug-metabolism enzyme superfamily involved in the glucuronidation of endobiotics and xenobiotics in humans. Many polymorphisms in UGT1A genes are reported to inhibit or decrease UGT1A activity. In this study, two UGT1A1 allozymes, UGT1A1 wild-type and a splice mutant, as well as UGT1A9 wild-type and its three UGT1A9 allozymes, UGT1A9*2(C3Y), UGT1A9*3(M33T), and UGT1A9*5(D256N) were single- or double-expressed in a Bac-to-Bac expression system. Dimerization of UGT1A1 or UGT1A9 allozymes was observed via fluorescence resonance energy transfer (FRET) and co-immunoprecipitation analysis. SNPs of UGT1A altered the ability of protein-protein interaction, resulting in differential FRET efficiencies and donor-acceptor r distances. Dimerization changed the chemical regioselectivity, substrate-binding affinity, and enzymatic activity of UGT1A1 and UGT1A9 in glucuronidation of quercetin. These findings provide molecular insights into the consequences of homozygous and heterozygous UGT1A1 and UGT1A9 allozymes expression on quercetin glucuronidation. PMID:27025983

  9. The bioflavonoid quercetin synergises with PPAR-γ agonist pioglitazone in reducing angiotensin-II contractile effect in fructose-streptozotocin induced diabetic rats.

    PubMed

    Kunasegaran, Thubasni; Mustafa, Mohd Rais; Murugan, Dharmani Devi; Achike, Francis I

    2016-06-01

    This study investigated the effects of combined minimal concentrations of quercetin and pioglitazone on angiotensin II-induced contraction of the aorta from fructose-streptozotocin (F-STZ)-induced type 2 diabetic rats and the possible role of superoxide anions (O2(-)) and nitric oxide (NO) in their potential therapeutic interaction. Contractile responses to Ang II of aortic rings from Sprague-Dawley (SD) and F-STZ rats were tested following pre-incubation of the tissues in the vehicle (DMSO; 0.05%), quercetin (Q, 0.1 μM), pioglitazone (P, 0.1 μM) or their combination (P + Q; 0.1 μM each). The amount of superoxide anion was evaluated by lucigenin-enhanced chemiluminescence and dihydroethidium fluorescence, and NO by assay of total nitrate/nitrite, and 4-Amino-5-Methylamino-2',7'-Difluorofluorescein (DAF-FM) diacetate. The synergistic reduction of Ang II-induced contraction of diabetic but not normal aorta with minimally effective concentrations of P + Q occurs through inhibiting O2(-) and increasing NO bioavailability. This finding opens the possibility of maximal vascular protective/antidiabetic effects with low dose pioglitazone combined with quercetin, thus minimizing the risk of adverse effects. PMID:27012965

  10. Tuning the inflammatory response to silver nanoparticles via quercetin in Caco-2 (co-)cultures as model of the human intestinal mucosa.

    PubMed

    Martirosyan, Alina; Grintzalis, Konstantinos; Polet, Madeleine; Laloux, Laurie; Schneider, Yves-Jacques

    2016-06-24

    Interaction of nanoparticles with food matrix components may cause unpredictable health complications. Using an improved Caco-2 cell-based in vitro (co-)culture model the potential of quercetin as one of the major food flavonoids to alter the effect of silver nanoparticles (Ag-NPs) <20 nm in the human intestinal mucosa at real life concentrations was investigated. Ag-NPs (15-90 μg/ml) decreased cell viability and reduced thiol groups, induced oxidative/nitrosative stress and lipid peroxidation and led to activity changes of various antioxidant enzymes after 3h exposure. The contribution of Ag(+) ions within the concentrations released from nanoparticles was shown to be less important, compared to Ag-NPs. While leading to inflammatory response in the intestines, Ag-NPs, paradoxically, also showed a potential anti-infammatory effect manifested in down-regulated IL-8 levels. Quercetin, co-administered with Ag-NPs, led to a reduction of cytotoxicity, oxidative stress, and recovered metabolic activity of Caco-2 cells, suggesting the protective effects of this flavonoid against the harmful effect of Ag-NPs. Quercetin not only alleviated the effect of Ag-NPs on the gastrointestinal cells, but also demonstrated a potential to serve as a tool for reversible modulation of intestinal permeability. PMID:27113704

  11. 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

  12. 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

  13. Quercetin does not alter the oral bioavailability of Atorvastatin in rats.

    PubMed

    Koritala, Rekha; Challa, Siva Reddy; Ragam, Satheesh Kumar; Geddam, Lal Babu; Venkatesh Reddy Challa, Venkatesh Reddy; Devi, Renuka; Sattenapalli, Srinu; Babu, Narendra

    2015-09-01

    The study was undertaken to evaluate the effect of Quercetin on the pharmacokinetics of Atorvastatin Calcium. In-vivo Pharmacokinetic studies were performed on rats in a single dose study and multiple dose study. Rats were treated with Quercetin (10 mg/kg) and Atorvastatin Calcium (20 mg/kg) orally and blood samples were collected at (0) pretreatment and 0.5, 1, 1.5, 2, 2.5, 3, 4, 8, 12, 24 hours post treatment. Plasma concentrations of Atorvastatin were estimated by HPLC method. Quercetin treatment did not significantly alter the pharmacokinetic parameters of atorvastatin like AUC(0-24), AUC(0-α) , T(max), C(max) and T(½) in both single dose and multiple dose studies of Atorvastatin Calcium. Quercetin does not alter the oral bioavailability of Atorvastatin Calcium in rats. PMID:26408869

  14. Exploration of the kinetic and thermochemical abilities for the free radical scavenging of two quercetin conformers

    NASA Astrophysics Data System (ADS)

    Mendoza-Wilson, Ana María; Sotelo-Mundo, Rogerio R.; Balandrán-Quintana, René R.; Glossman-Mitnik, Daniel; Sántiz-gómez, Marco a.; García-orozco, karina D.

    2010-09-01

    Quercetin has a great antioxidant potential due to its large capacity for free radical scavenging. Although it has been found that conformational changes have a profound effect on its chemical properties, there are few studies where conformation is associated with the antioxidant activity. The aim of this investigation was to explore the kinetic and the thermochemical abilities of two quercetin conformers for the free radical scavenging. Quercetin unhydrate (QUH) and quercetin dihydrate (QDH) conformers were studied employing 2,2-diphenyl-1-picrylhydrazyl (DPPH rad ) as in vitro radical model, and catechol and 4-hexyl-resorcinol as reference systems, for identifying the oxidation products. QDH showed to be most effective under conditions of free radical excess, while QUH was most effective when the flavonoid far exceeds the concentration of free radical. It was found, by means of experimental and computational methods, that 4'-OH, 3-OH and 3'-OH are the main reactive sites of both conformers.

  15. Quercetin 7-O-glucoside suppresses nitrite-induced formation of dinitrosocatechins and their quinones in catechin/nitrite systems under stomach simulating conditions.

    PubMed

    Morina, Filis; Takahama, Umeo; Yamauchi, Ryo; Hirota, Sachiko; Veljovic-Jovanovic, Sonja

    2015-01-01

    Foods of plant origin contain flavonoids. In the adzuki bean, (+)-catechin, quercetin 3-O-rutinoside (rutin), and quercetin 7-O-β-D-glucopyranoside (Q7G) are the major flavonoids. During mastication of foods prepared from the adzuki bean, the flavonoids are mixed with saliva and swallowed into the stomach. Here we investigated the interactions between Q7G and (+)-catechin at pH 2, which may proceed in the stomach after the ingestion of foods prepared from the adzuki bean. Q7G reacted with nitrous acid producing nitric oxide (˙NO) and a glucoside of 2-(3,4-dihydroxybenzoyl)-2,4,6-trihydroxy-3(2H)-benzofuranone. (+)-Catechin reacted with nitrous acid producing ˙NO and 6,8-dinitrosocatechin. The production of the dinitrosocatechin was partly suppressed by Q7G, and the suppression resulted in the enhancement of Q7G oxidation. 6,8-Dinitrosocatechin reacted further with nitrous acid generating the o-quinone, and the quinone formation was effectively suppressed by Q7G. In the flavonoids investigated, the suppressive effect decreased in the order Q7G≈quercetin>kaempferol>quercetin 4'-O-glucoside>rutin. Essentially the same results were obtained when (-)-epicatechin was used instead of (+)-catechin. The results indicate that nitrous acid-induced formation of 6,8-dinitrosocatechins and the o-quinones can be suppressed by flavonols in the stomach, and that both a hydroxyl group at C3 and ortho-hydroxyl groups in the B-ring are required for efficient suppression. PMID:25375233

  16. Effect of quercetin and its metabolite on caveolin-1 expression induced by oxidized LDL and lysophosphatidylcholine in endothelial cells.

    PubMed

    Kamada, Chiemi; Mukai, Rie; Kondo, Akari; Sato, Shinya; Terao, Junji

    2016-05-01

    Oxidized low-density lipoprotein contributes to atherosclerotic plaque formation, and quercetin is expected to exert anti-atherosclerotic effects. We previously reported accumulation of conjugated quercetin metabolites in the aorta of rabbits fed high-cholesterol diets with quercetin glucosides, resulting in attenuation of lipid peroxidation and inhibition of lipid accumulation. Caveolin-1, a major structural protein of caveolae in vascular endothelial cells, plays a role in atherosclerosis development. Here we investigated effects of oxidized low-density lipoprotein, quercetin and its metabolite, quercetin 3-O-β-glucuronide, on caveolin-1 expression. Oxidized low-density lipoprotein significantly upregulated caveolin-1 mRNA expression. An oxidized low-density lipoprotein component, lysophosphatidylcholine, also induced expression of both caveolin-1 mRNA and protein. However, lysophosphatidylcholine did not affect the location of caveolin-1 proteins within caveolae structures. Co-treatment with quercetin or quercetin 3-O-β-glucuronide inhibited lysophosphatidylcholine-induced caveolin-1 expression. Quercetin and quercetin 3-O-β-glucuronide also suppressed expression of adhesion molecules induced by oxidized low-density lipoprotein and lysophosphatidylcholine. These results strongly suggest lysophosphatidylcholine derived from oxidized low-density lipoprotein contributes to atherosclerotic events by upregulating caveolin-1 expression, resulting in induction of adhesion molecules. Quercetin metabolites are likely to exert an anti-atherosclerotic effect by attenuating caveolin-1 expression in endothelial cells. PMID:27257344

  17. Effect of quercetin and its metabolite on caveolin-1 expression induced by oxidized LDL and lysophosphatidylcholine in endothelial cells

    PubMed Central

    Kamada, Chiemi; Mukai, Rie; Kondo, Akari; Sato, Shinya; Terao, Junji

    2016-01-01

    Oxidized low-density lipoprotein contributes to atherosclerotic plaque formation, and quercetin is expected to exert anti-atherosclerotic effects. We previously reported accumulation of conjugated quercetin metabolites in the aorta of rabbits fed high-cholesterol diets with quercetin glucosides, resulting in attenuation of lipid peroxidation and inhibition of lipid accumulation. Caveolin-1, a major structural protein of caveolae in vascular endothelial cells, plays a role in atherosclerosis development. Here we investigated effects of oxidized low-density lipoprotein, quercetin and its metabolite, quercetin 3-O-β-glucuronide, on caveolin-1 expression. Oxidized low-density lipoprotein significantly upregulated caveolin-1 mRNA expression. An oxidized low-density lipoprotein component, lysophosphatidylcholine, also induced expression of both caveolin-1 mRNA and protein. However, lysophosphatidylcholine did not affect the location of caveolin-1 proteins within caveolae structures. Co-treatment with quercetin or quercetin 3-O-β-glucuronide inhibited lysophosphatidylcholine-induced caveolin-1 expression. Quercetin and quercetin 3-O-β-glucuronide also suppressed expression of adhesion molecules induced by oxidized low-density lipoprotein and lysophosphatidylcholine. These results strongly suggest lysophosphatidylcholine derived from oxidized low-density lipoprotein contributes to atherosclerotic events by upregulating caveolin-1 expression, resulting in induction of adhesion molecules. Quercetin metabolites are likely to exert an anti-atherosclerotic effect by attenuating caveolin-1 expression in endothelial cells. PMID:27257344

  18. 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

  19. Quercetin-induced downregulation of phospholipase D1 inhibits proliferation and invasion in U87 glioma cells

    SciTech Connect

    Park, Mi Hee; Min, Do Sik

    2011-09-09

    Highlights: {yields} Quercetin, a bioactive flavonoid, suppresses expression and enzymatic activity of phospholipase D1. {yields} Quercetin abolishes NFkB-induced phospholipase D1 expression via inhibition of NFkB transactivation. {yields} Quercetin-induced suppression of phospholipase D1 inhibits invasion and proliferation of human glioma cells. -- Abstract: Phospholipase D (PLD) has been recognized as a regulator of cell proliferation and tumorigenesis, but little is known about the molecules regulating PLD expression. Thus, the identification of small molecules inhibiting PLD expression would be an important advance in PLD-mediated physiology. Quercetin, a ubiquitous bioactive flavonoid, is known to inhibit proliferation and induce apoptosis in a variety of cancer cells. In the present study, we examined the effect of quercetin on the expression of PLD in U87 glioma cells. Quercetin significantly suppressed the expression of PLD1 at the transcriptional level. Moreover, quercetin abolished the protein expression of PLD1 in a time and dose-dependent manner, as well as inhibited PLD activity. Quercetin suppressed NF{kappa}B-induced PLD1 expression via inhibition of NFkB transactivation. Furthermore, quercetin inhibited activation and invasion of metalloproteinase-2 (MMP-2), a key modulator of glioma cell invasion, induced by phosphatidic acid (PA), a product of PLD activity. Taken together these data demonstrate that quercetin abolishes PLD1 expression and subsequently inhibits invasion and proliferation of glioma cells.

  20. Anticancer effect and mechanism of polymer micelle-encapsulated quercetin on ovarian cancer

    NASA Astrophysics Data System (ADS)

    Gao, Xiang; Wang, Bilan; Wei, Xiawei; Men, Ke; Zheng, Fengjin; Zhou, Yingfeng; Zheng, Yu; Gou, Maling; Huang, Meijuan; Guo, Gang; Huang, Ning; Qian, Zhiyong; Wei, Yuquan

    2012-10-01

    Encapsulation of hydrophobic agents in polymer micelles can improve the water solubility of cargos, contributing to develop novel drugs. Quercetin (QU) is a hydrophobic agent with potential anticancer activity. In this work, we encapsulated QU into biodegradable monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) micelles and tried to provide proof-of-principle for treating ovarian cancer with this nano-formulation of quercetin. These QU loaded MPEG-PCL (QU/MPEG-PCL) micelles with drug loading of 6.9% had a mean particle size of 36 nm, rendering the complete dispersion of quercetin in water. QU inhibited the growth of A2780S ovarian cancer cells on a dose dependent manner in vitro. Intravenous administration of QU/MPEG-PCL micelles significantly suppressed the growth of established xenograft A2780S ovarian tumors through causing cancer cell apoptosis and inhibiting angiogenesis in vivo. Furthermore, the anticancer activity of quercetin on ovarian cancer cells was studied in vitro. Quercetin treatment induced the apoptosis of A2780S cells associated with activating caspase-3 and caspase-9. MCL-1 downregulation, Bcl-2 downregulation, Bax upregulation and mitochondrial transmembrane potential change were observed, suggesting that quercetin may induce apoptosis of A2780S cells through the mitochondrial apoptotic pathway. Otherwise, quercetin treatment decreased phosphorylated p44/42 mitogen-activated protein kinase and phosphorylated Akt, contributing to inhibition of A2780S cell proliferation. Our data suggested that QU/MPEG-PCL micelles were a novel nano-formulation of quercetin with a potential clinical application in ovarian cancer therapy.

  1. 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

  2. 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

  3. A novel solid fluorescence method for the fast determination of quercetin in biological samples based on the quercetin-Al(III) complex imprinted polymer

    NASA Astrophysics Data System (ADS)

    Hu, Yufei; Feng, Ting; Li, Gongke

    2014-01-01

    In this work, a novel solid fluorescence method was proposed and applied to the fast determination of quercetin in urine and onion skin samples by using metal coordination imprinted polymer membrane, which was regarded as a recognition element. The quercetin-Al(III) imprinted polymer was immobilized in the microporous polypropylene fiber membrane via consecutive in situ polymerization. The CIP membrane had the porous, loose and layer upon layer structure. The CIP membrane was characterized by electron microscope photographs, infrared spectra, thermogravimetric analysis and solvent-resistant investigation. The extraction conditions including extraction solvent, extraction time, desorption solvent were optimized. Compared with MIP and NIP membrane, CIP membrane had been proved to be peculiar selective for quercetin even in presence of the structurally similar compounds such as kaempferol, rutin, naringenin and alpinetin. The CIP membrane was characteristic of high selectivity, stable and sensitive response to quercetin in polar environment. Under the optimum condition, there was a linear relationship between the state fluorescent response and the concentration of quercetin. The linear calibration range was over 0.02 mg L-1-0.80 mg L-1 with a detection limit of 5 μg L-1. The method was characteristic of flexible and good repeatability with relative standard deviation (RSD) of 4.1%. The proposed method was also successfully applied for the determination of quercetin in urine and onion skin samples without complicated pretreatment. The recoveries were 84.0-112.4% and RSDs varied from 1.5% to 6.8%. The results obtained by the proposed method agreed well with those obtained by HPLC method.

  4. Potential of Excipient Emulsions for Improving Quercetin Bioaccessibility and Antioxidant Activity: An in Vitro Study.

    PubMed

    Chen, Xing; Zou, Liqiang; Liu, Wei; McClements, David Julian

    2016-05-11

    The potential for excipient emulsions to enhance the bioaccessibility and antioxidant activity of quercetin was determined in this study. Oil-in-water excipient emulsions containing two levels (4 or 10%) of small lipid droplets (d < 250 nm) were prepared from a long-chain triglyceride (corn oil). The solubilization of quercetin by the excipient emulsions was faster than by bulk corn oil or bulk water, and the solubilization rate was higher at 100 °C than at 30 °C. The bioaccessibility of quercetin samples was determined using an in vitro gastrointestinal model, and the bioactivity of quercetin was determined using a rat feeding study. The excipient emulsions were more effective at enhancing quercetin bioaccessibility and rat plasma antioxidant activity than either bulk oil or bulk water. This effect was attributed to the rapid digestion of the long chain triglycerides when they were in an emulsified form, which led to the rapid production of mixed micelles capable of solubilizing, protecting, and transporting quercetin. PMID:27136205

  5. Protective effect of rosiglitazone, quercetin, and their combination on fructose-induced metabolic syndrome in rats

    PubMed Central

    Abo-youssef, Amira M.

    2015-01-01

    Objectives: Quercetin exhibits a wide range of biological functions. The present study aimed to investigate the possible beneficial effects of rosiglitazone, quercetin as well as their combination on metabolic and biochemical changes associated with the fructose-induced metabolic syndrome (MS). Materials and Methods: Four groups of rats were fed on fructose-enriched diet for 14 weeks. One group served as fructose-enriched diet control, while the remaining groups were treated with rosiglitazone (4 mg/kg/day), quercetin (50 mg/kg/day), and their combination during the last 4 weeks. A fifth group was fed on normal laboratory diet. At the end of the experiment, blood samples were withdrawn for the estimation of markers of MS. Results: Rosiglitazone or quercetin attenuated the biochemical and metabolic changes associated with MS. The combination of rosiglitazone and quercetin nearly normalized these changes. Conclusion: Quercetin, as well as its combination with rosiglitazone, showed beneficial protective effects against metabolic and biochemical changes associated with MS. PMID:26729953

  6. Quercetin inhibits advanced glycation end product formation by trapping methylglyoxal and glyoxal.

    PubMed

    Li, Xiaoming; Zheng, Tiesong; Sang, Shengmin; Lv, Lishuang

    2014-12-17

    Methylglyoxal (MGO) and glyoxal (GO) not only are endogenous metabolites but also exist in exogenous resources, such as foods, beverages, urban atmosphere, and cigarette smoke. They have been identified as reactive dicarbonyl precursors of advanced glycation end products (AGEs), which have been associated with diabetes-related long-term complications. In this study, quercetin, a natural flavonol found in fruits, vegetables, leaves, and grains, could effectively inhibit the formation of AGEs in a dose-dependent manner via trapping reactive dicarbonyl compounds. More than 50.5% of GO and 80.1% of MGO were trapped at the same time by quercetin within 1 h under physiological conditions. Quercetin and MGO (or GO) were combined at different ratios, and the products generated from this reaction were analyzed with LC-MS. Both mono-MGO and di-MGO adducts of quercetin were detected in this assay using LC-MS, but only tiny amounts of mono-GO adducts of quercetin were found. Additionally, di-MGO adducts were observed as the dominant product with prolonged incubation time. In the bovine serum albumin (BSA)-MGO/GO system, quercetin traps MGO and GO directly and then significantly inhibits the formation of AGEs. PMID:25412188

  7. 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

  8. Quercetin regulates β-catenin signaling and reduces the migration of triple negative breast cancer.

    PubMed

    Srinivasan, Asha; Thangavel, Chellappagounder; Liu, Yi; Shoyele, Sunday; Den, Robert B; Selvakumar, Ponniah; Lakshmikuttyamma, Ashakumary

    2016-05-01

    Triple negative breast cancer (TNBC) is characterized by a lack in estrogen, progesterone, and epidermal growth factor 2 receptors. TNBC exhibits most of the characteristics of basal-like and claudin-low breast cancer subtypes. The main contributor in the mortality of TNBC is due to the higher invasive and migratory ability of these tumor cells. Some plant flavonoids inhibit the epithelial mesenchymal transition (EMT) of tumor cells and suppress cancer metastasis. In this study, we aimed to determine whether the flavonoid quercetin is effective in modulating the molecular signaling associated with EMT in TNBC. Our data indicated that quercetin can induce the expression of E-cadherin and also downregulate vimentin levels in TNBC. The ability of quercetin to modulate these EMT markers resulted in a mesenchymal-to-epithelial transition (MET). Quercetin-induced MET was linked with the alteration of nuclear localization of β-catenin and modulation of β-catenin target genes such as cyclin D1 and c-Myc. Furthermore, we observed that quercetin induced the anti-tumor activity of doxorubicin by inhibiting the migratory ability of TNBC cells. These results suggested that quercetin may inhibit TNBC metastasis and also improve the therapeutic efficacy of existing chemotherapeutic drugs. © 2015 Wiley Periodicals, Inc. PMID:25968914

  9. 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

  10. The impact of quercetin on cisplatin-induced clastogenesis and apoptosis in murine marrow cells.

    PubMed

    Attia, Sabry M

    2010-05-01

    The aim of the present investigation is to determine whether the quercetin in combination with cisplatin can ameliorate cisplatin-induced clastogenesis and apoptosis in the bone marrow cells of mice. The scoring of chromosomal aberrations, micronuclei and mitotic activity were undertaken in the current study as markers of clastogenicity. Apoptosis was analysed by the Annexin V-propidium iodide assay and the occurrence of a hypodiploid DNA peak. Oxidative stress markers such as bone marrow lipid peroxidation and reduced glutathione were assessed as a possible mechanism underlying this amelioration. Quercetin was neither clastogenic nor apoptogenic in mice at doses equivalent to 50 or 100 mg/kg for 2 days. Pre-treatment of mice with quercetin significantly reduced cisplatin-induced clastogenesis and apoptosis in the bone marrow cells and these effects were dose and time dependent. Prior administration of quercetin ahead of cisplatin challenge ameliorated oxidative stress markers. Overall, this study provides for the first time that quercetin has a protective role in the abatement of cisplatin-induced clastogenesis and apoptosis in the bone marrow cells of mice that resides, at least in part, in its antioxidant effects. Therefore, quercetin can be a good candidate to decrease the deleterious effects of cisplatin in the bone marrow cells of cancer patients treated with this drug. PMID:20156843

  11. 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

  12. Development of an antioxidant biomaterial by promoting the deglycosylation of rutin to isoquercetin and quercetin.

    PubMed

    Cruz-Zúñiga, Johana M; Soto-Valdez, Herlinda; Peralta, Elizabeth; Mendoza-Wilson, Ana María; Robles-Burgueño, M Refugio; Auras, Rafael; Gámez-Meza, Nohemí

    2016-08-01

    Quercetin-3-O-rutinoside (rutin), quercetin-3-O-glucoside (isoquercetin) and quercetin have shown antioxidant, cytoprotective, vasoprotective, antiproliferative and antiinflammatory properties. The aim of this work was to determine the conversion of rutin to isoquercetin and quercetin during the production of poly(l-lactic acid) films with potential to deliver these flavonoids toward tissues, pharmaceuticals or food matrices. Three poly(l-lactic acid) formulations with 17.7, 39.6 and 39.1mg/g of rutin were prepared by the extrusion process. Processing temperatures (130-165°C) promoted the deglycosylation of rutin to produce isoquercetin and subsequently quercetin, identified by high performance liquid chromatography coupled to mass spectrometry. The effect of the process on the antioxidant activity of the films was determined by measuring the capacity to scavenge 2,2 diphenyl-1-picrylhydrazyl radicals. The material with the highest proportion of quercetin showed the highest antioxidant activity which could be used to produce delivering devices of the flavonoids to tissues, pharmaceuticals or food matrices. PMID:26988520

  13. 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

  14. Quercetin protects human peripheral blood mononuclear cells from OTA-induced oxidative stress, genotoxicity, and inflammation.

    PubMed

    Periasamy, Ramyaa; Kalal, Iravathy Goud; Krishnaswamy, Rajashree; Viswanadha, VijayaPadma

    2016-07-01

    Ochratoxin A (OTA) is one of the most abundant food-contaminating mycotoxins world wide, and is detrimental to human and animal health. This study evaluated the protective effect of quercetin against OTA-induced cytotoxicity, genotoxicity, and inflammatory response in lymphocytes. Cytotoxicity determined by MTT assay revealed IC20 value of OTA to be 20 µM, which was restored to near control values by pretreatment with quercetin. Oxidative stress parameters such as antioxidant enzymes, LPO and PCC levels indicated that quercetin exerted a protective effect on OTA-induced oxidative stress. Quercetin exerted an antigenotoxic effect on OTA-induced genotoxicity, by significantly reducing the number of structural aberrations in chromosomes and comet parameters like, % olive tail moment from 2.76 ± 0.02 to 0.56 ± 0.02 and % tail DNA from 56.23 ± 2.56 to 12.36 ± 0.56 as determined by comet assay. OTA-induced NO, TNF-α, IL-6, and IL-8 were significantly reduced in the quercetin pretreated samples indicating its anti-inflammatory role. Our results demonstrate for the first time that quercetin exerts a cytoprotective effect against OTA-induced oxidative stress, genotoxicity, and inflammation in lymphocytes. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 855-865, 2016. PMID:25532488

  15. Quercetin suppresses cellular migration and invasion in human head and neck squamous cell carcinoma (HNSCC).

    PubMed

    Chan, Chien-Yi; Lien, Chia-Hsien; Lee, Ming-Fen; Huang, Chun-Yin

    2016-06-01

    Head and neck squamous cell carcinoma (HNSCC) with aberrant epidermal growth factor receptor (EGFR) signaling is often associated with a poor prognosis and a low survival rate. Hence, efficient inhibition of the EGFR signaling-mediated malignancy would improve survival rate. In a previous study, we demonstrated that quercetin appears to be a potent anti-tumorigenic agent through its inhibition of the EGFR/Akt pathway in oral cancer, but its anti-metastatic potential in HNSCC remains unclear [1]. Here, we have hypothesized that quercetin might be effective in metastatic inhibition in EGFR-overexpressing HNSCC cells. Quercetin treatment with 10 μM (half concentration of IC50) suppressed cell migration and invasion in EGFR-overexpressing HSC-3 and FaDu HNSCC cells. Quercetin also inhibited the colony growth of HSC-3 cells embedded in a Matrigel matrix. Among matrix metalloproteinases (MMPs), the secreted gelatinases MMP-2 and MMP-9 are responsible for the degradation of gelatin in the extracellular matrix and type IV collagen in the basement membrane; and this degradation event is crucial for the migration from the origin and the invasion into the bone in HNSCC. Quercetin (10 μM) treatment also suppressed the expression and proteolytic activity of MMP-2 and MMP-9. Taken together, our data indicate that quercetin is an effective anti-cancer agent against MMP-2- and MMP-9-mediated metastasis in EGFR-overexpressing HNSCC. PMID:27510965

  16. Quercetin/beta-cyclodextrin solid complexes prepared in aqueous solution followed by spray-drying or by physical mixture.

    PubMed

    Borghetti, Greice S; Lula, Ivana S; Sinisterra, Ruben D; Bassani, Valquiria L

    2009-01-01

    The present study was designed to investigate the influence of operating conditions (temperature, stirring time, and excess amount of quercetin) on the complexation of quercetin with beta-cyclodextrin using a 2(3) factorial design. The highest aqueous solubility of quercetin was reached under the conditions 37 degrees C/24 h/6 mM of quercetin. The stoichiometric ratio (1:1) and the apparent stability constant (Ks = 230 M(-1)) of the quercetin/beta-cyclodextrin complex were determined using phase-solubility diagrams. The semi-industrial production of a 1:1 quercetin/beta-cyclodextrin solid complex was carried out in aqueous solution followed by spray-drying. Although the yield of the spray-drying process was adequate (77%), the solid complex presented low concentration of quercetin (0.14%, w/w) and, thus, low complexation efficiency. The enhancement of aqueous solubility of quercetin using this method was limited to 4.6-fold in the presence of 15 mM of beta-cyclodextrin. Subsequently, an inclusion complex was prepared via physical mixture of quercetin with beta-cyclodextrin (molar ratio of 1:1 and quercetin concentration of 23% (w/w)) and characterized using infrared spectroscopy, differential scanning calorimetry, nuclear magnetic resonance spectroscopy, and scanning electron microscopy analyses. The enhancement of aqueous solubility of quercetin using this method was 2.2-fold, similar to that found in the complex prepared in aqueous solution before the spray-drying process (2.5-fold at a molar ratio of 1:1, i.e., 6 mM of quercetin and 6 mM of beta-cyclodextrin). PMID:19280349

  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. 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

  19. Kinetic spectrophotometric determination of certain cephalosporins using oxidized quercetin reagent

    NASA Astrophysics Data System (ADS)

    Saleh, Gamal A.; El-Shaboury, Salwa R.; Mohamed, Fardous A.; Rageh, Azza H.

    2009-09-01

    A simple, precise and accurate kinetic spectrophotometric method for determination of cefoperazone sodium, cefazolin sodium and ceftriaxone sodium in bulk and in pharmaceutical formulations has been developed. The method is based upon a kinetic investigation of the reaction of the drug with oxidized quercetin reagent at room temperature for a fixed time of 30 min. The decrease in absorbance after the addition of the drug was measured at 510 nm. The absorbance concentration plot was rectilinear over the range 80-400 μg mL -1 for all studied drugs. The concentration of the studied drugs was calculated using the corresponding calibration equation for the fixed time method. The determination of the studied drugs by initial rate, variable time and rate-constant methods was feasible with the calibration equations obtained but the fixed time method has been found to be more applicable. The analytical performance of the method, in terms of accuracy and precision, was statistically validated; the results were satisfactory. The method has been successfully applied to the determination of the studied drugs in commercial pharmaceutical formulations. Statistical comparison of the results with a well established reported method showed excellent agreement and proved that there is no significant difference in the accuracy and precision.

  20. 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

  1. Enhanced electrochemical detection of quercetin by Natural Deep Eutectic Solvents.

    PubMed

    Gomez, Federico José Vicente; Espino, Magdalena; de Los Angeles Fernandez, María; Raba, Julio; Silva, María Fernanda

    2016-09-14

    New trends in analytical chemistry encourage the development of smart techniques and methods aligned with Green Chemistry. In this sense, Natural Deep Eutectic Solvents represents an excellent opportunity as a new generation of green solvents. In this work a new application for them has been proposed and demonstrated. These solvents were synthesized by combinations of inexpensive and natural components like, Glucose, Fructose, Citric acid and Lactic acid. The different natural solvents were easily prepared and added to buffer solution in different concentrations, allowing the enhancement of electrochemical detection of an important representative antioxidant like quercetin (QR) with improved signal up to 380%. QR is a ubiquitous flavonoid widespread in plants and food of plant origin. The proposed method using phosphate buffer with a eutectic mixture of Citric acid, Glucose and water in combination with carbon screen printed electrodes exhibited a good analytical performance. Detection and quantification limits were of 7.97 and 26.3 nM respectively; and repeatability with %RSDs of 1.41 and 7.49 for peak potential and intensity respectively. In addition, it has proved to be faster, greener and cheaper than other sensors and chromatographic methods available with the additional advantage of being completely portable. Furthermore, the obtained results demonstrated that the proposed method is able for the determination of QR in complex food samples. PMID:27566343

  2. Quercetin reduces obesity-associated ATM infiltration and inflammation in mice: a mechanism including AMPKα1/SIRT1.

    PubMed

    Dong, Jing; Zhang, Xian; Zhang, Lei; Bian, Hui-Xi; Xu, Na; Bao, Bin; Liu, Jian

    2014-03-01

    Adipose tissue macrophage (ATM) plays a central role in obesity-associated inflammation and insulin resistance. Quercetin, a dietary flavonoid, possesses anti-inflammation and anti-insulin resistance properties. However, it is unclear whether quercetin can alleviate high-fat diet (HFD)-induced ATM infiltration and inflammation in mice. In this study, 5-week-old C57BL/6 mice were fed low-fat diet, HFD, or HFD with 0.l% quercetin for 12 weeks, respectively. Dietary quercetin reduced HFD-induced body weight gain and improved insulin sensitivity and glucose intolerance in mice. Meanwhile, dietary quercetin enhanced glucose transporter 4 translocation and protein kinase B signal in epididymis adipose tissues (EATs), suggesting that it heightened glucose uptake in adipose tissues. Histological and real-time PCR analysis revealed that quercetin attenuated mast cell and macrophage infiltration into EATs in HFD-fed mice. Dietary quercetin also modified the phenotype ratio of M1/M2 macrophages, lowered the levels of proinflammatory cytokines, and enhanced adenosine monophosphate-activated protein kinase (AMPK) α1 phosphorylation and silent information regulator 1 (SIRT1) expression in EATs. Further, using AMPK activator 5-aminoimidazole-4-carboxamide-1-β4-ribofuranoside and inhibitor Compound C, we found that quercetin inhibited polarization and inflammation of mouse bone marrow-derived macrophages through an AMPKα1/SIRT1-mediated mechanism. In conclusion, dietary quercetin might suppress ATM infiltration and inflammation through the AMPKα1/SIRT1 pathway in HFD-fed mice. PMID:24465016

  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. 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

  5. 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

  6. 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

  7. Protective effect of quercetin on skeletal and neural tube teratogenicity induced by cyclophosphamide in rat fetuses

    PubMed Central

    Khaksary Mahabady, Mahmood; Gholami, Mohammad Reza; Najafzadeh Varzi, Hossein; Zendedel, Abolfazl; Doostizadeh, Mona

    2016-01-01

    Cyclophosphamide (CP) is a drug commonly used to treat neoplastic disease and some autoimmune diseases. It is also a well-known and well-studied teratogen causing a variety of birth defects in fetuses of pregnant women treated with the drug. There are many reports that show the adverse effects of CP can be decreased by use of antioxidant drugs. It appears that, quercetin has antioxidant effect. The aim of this study was prevention or decrease of teratogenicity of CP in fetuses of rats by quercetin. This study was performed on 35 pregnant rats divided into six groups. Control group was received normal saline (5 mL kg-1, intraperitoneally) and 2-6 groups received a single dose of CP (15 mg kg-1), a single dose of quercetin (75 or 200 mg kg-1), CP plus quercetin (75 or 200 mg kg-1) intraperitoneally at 9th day of gestation, respectively. Fetuses were collected at 20th day of gestation and after determination of weight and crown rump length were stained by alizarin red – alcian blue method and skeletal system were examined by stereomicroscope. The results showed that the cleft palate, exencephaly, spina bifida and omphalocele incidence were 55.56%, 27.77%, 33.34% and 11.11%, in fetuses of rat that received only CP, respectively. However, it decreased to 16.00%, 16.00%, 16.00% and 8.00% by quercetin (75 mg kg-1) and so to 12.90%, 12.90%, 6.45% and 3.28% by quercetin (200 mg kg-1), respectively. On the basis of results, quercetin significantly can decrease teratogenicity induced by CP. PMID:27482358

  8. 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

  9. 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

  10. Protective effect of quercetin on skeletal and neural tube teratogenicity induced by cyclophosphamide in rat fetuses.

    PubMed

    Khaksary Mahabady, Mahmood; Gholami, Mohammad Reza; Najafzadeh Varzi, Hossein; Zendedel, Abolfazl; Doostizadeh, Mona

    2016-01-01

    Cyclophosphamide (CP) is a drug commonly used to treat neoplastic disease and some autoimmune diseases. It is also a well-known and well-studied teratogen causing a variety of birth defects in fetuses of pregnant women treated with the drug. There are many reports that show the adverse effects of CP can be decreased by use of antioxidant drugs. It appears that, quercetin has antioxidant effect. The aim of this study was prevention or decrease of teratogenicity of CP in fetuses of rats by quercetin. This study was performed on 35 pregnant rats divided into six groups. Control group was received normal saline (5 mL kg(-1), intraperitoneally) and 2-6 groups received a single dose of CP (15 mg kg(-1)), a single dose of quercetin (75 or 200 mg kg(-1)), CP plus quercetin (75 or 200 mg kg(-1)) intraperitoneally at 9(th) day of gestation, respectively. Fetuses were collected at 20(th) day of gestation and after determination of weight and crown rump length were stained by alizarin red - alcian blue method and skeletal system were examined by stereomicroscope. The results showed that the cleft palate, exencephaly, spina bifida and omphalocele incidence were 55.56%, 27.77%, 33.34% and 11.11%, in fetuses of rat that received only CP, respectively. However, it decreased to 16.00%, 16.00%, 16.00% and 8.00% by quercetin (75 mg kg(-1)) and so to 12.90%, 12.90%, 6.45% and 3.28% by quercetin (200 mg kg(-1)), respectively. On the basis of results, quercetin significantly can decrease teratogenicity induced by CP. PMID:27482358

  11. 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

  12. Enhancing the anti-colon cancer activity of quercetin by self-assembled micelles.

    PubMed

    Xu, Guangya; Shi, Huashan; Ren, Laibin; Gou, Hongfeng; Gong, Daoyin; Gao, Xiang; Huang, Ning

    2015-01-01

    Colorectal cancer, a type of malignant neoplasm originating from the epithelial cells lining the colon and/or rectum, has been the third most frequent malignancy and one of the leading causes of cancer-related deaths in the US. As a bioflavonoid with high anticancer potential, quercetin (Qu) has been proved to have a prospective applicability in chemotherapy for a series of cancers. However, quercetin is a hydrophobic drug, the poor hydrophilicity of which hinders its clinical usage in cancer therapy. Therefore, a strategy to improve the solubility of quercetin in water and/or enhance the bioavailability is desired. Encapsulating the poorly water-soluble, hydrophobic agents into polymer micelles could facilitate the dissolution of drugs in water. In our study, nanotechnology was employed, and quercetin was encapsulated into the biodegradable nanosized amphiphilic block copolymers of monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL), attempting to present positive evidences that this drug delivery system of polymeric micelles is effective. The quercetin-loaded MPEG-PCL nanomicelles (Qu-M), with a high drug loading of 6.85% and a minor particle size of 34.8 nm, completely dispersed in the water and released quercetin in a prolonged period in vitro and in vivo. At the same time, compared with free quercetin, Qu-M exhibited improved apoptosis induction and cell growth inhibition effects in CT26 cells in vitro. Moreover, the mice subcutaneous CT26 colon cancer model was established to evaluate the therapy efficiency of Qu-M in detail, in which enhanced anti-colon cancer effect was proved in vivo: Qu-M were more efficacious in repressing the growth of colon tumor than free quercetin. In addition, better effects of Qu-M on inducing cell apoptosis, inhibiting tumor angiogenesis, and restraining cell proliferation were observed by immunofluorescence analysis. Our study indicated that Qu-M were a novel nanoagent of quercetin with an enhanced antitumor

  13. 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

  14. 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

  15. Quercetin Impacts Expression of Metabolism- and Obesity-Associated Genes in SGBS Adipocytes.

    PubMed

    Leiherer, Andreas; Stoemmer, Kathrin; Muendlein, Axel; Saely, Christoph H; Kinz, Elena; Brandtner, Eva M; Fraunberger, Peter; Drexel, Heinz

    2016-01-01

    Obesity is characterized by the rapid expansion of visceral adipose tissue, resulting in a hypoxic environment in adipose tissue which leads to a profound change of gene expression in adipocytes. As a consequence, there is a dysregulation of metabolism and adipokine secretion in adipose tissue leading to the development of systemic inflammation and finally resulting in the onset of metabolic diseases. The flavonoid quercetin as well as other secondary plant metabolites also referred to as phytochemicals have anti-oxidant, anti-inflammatory, and anti-diabetic effects known to be protective in view of obesity-related-diseases. Nevertheless, its underlying molecular mechanism is still obscure and thus the focus of this study was to explore the influence of quercetin on human SGBS (Simpson Golabi Behmel Syndrome) adipocytes' gene expression. We revealed for the first time that quercetin significantly changed expression of adipokine (Angptl4, adipsin, irisin and PAI-1) and glycolysis-involved (ENO2, PFKP and PFKFB4) genes, and that this effect not only antagonized but in part even overcompensated the effect mediated by hypoxia in adipocytes. Thus, these results are explained by the recently proposed hypothesis that the protective effect of quercetin is not solely due to its free radical-scavenging activity but also to a direct effect on mitochondrial processes, and they demonstrate that quercetin might have the potential to counteract the development of obesity-associated complications. PMID:27187453

  16. 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

  17. Quercetin induces bladder cancer cells apoptosis by activation of AMPK signaling pathway

    PubMed Central

    Su, Qiongli; Peng, Mei; Zhang, Yuqing; Xu, Wanjun; Darko, Kwame Oteng; Tao, Ting; Huang, Yanjun; Tao, Xiaojun; Yang, Xiaoping

    2016-01-01

    Quercetin, a natural existing polyphenol compound, has shown anticancer capacity for liver, breast, nasopharyngeal and prostate carcinoma but has not been clinically approved yet. This might be due to lack of clear mechanistic picture. Bladder cancer is one of the most common cancers of the urinary tract in the world. In China, bladder cancer has the highest rate of incidence out of all malignancies of the urinary system. The anticancer application of quercetin on bladder cancer has not been investigated either. This study was aimed to examine the mechanisms of quercetin on inhibition of bladder cancer. First, two human and one murine bladder cancer cell lines were tested in vitro for inhibitory sensitivity by MTT and cologenic assays. Second, AMPK pathway including 4E-BP1 and S6K were examined by western blot. Quercetin induces apoptosis and inhibits migration. We are the first to show that quercetin displays potent inhibition on bladder cancer cells via activation of AMPK pathway. PMID:27186419

  18. 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

  19. 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

  20. Different mechanisms of actions of genistein, quercetin on spontaneous contractions of rabbit duodenum.

    PubMed

    Santos-Fagundes, Diego; Grasa, Laura; Gonzalo, Sergio; Valero, Marta Sofía; Castro, Marta; Arruebo, María Pilar; Plaza, Miguel Ángel; Divina-Murillo, María

    2015-07-01

    Flavonoids are known to relax precontracted intestinal smooth muscle and delay intestinal transit or intestinal peristalsis. The aim of this study was to determine the effects of genistein and quercetin on spontaneous contractions of rabbit duodenum in vitro in an organ bath. Genistein and quercetin (0.1-10µM) reduced the amplitude of spontaneous contractions in the longitudinal and circular smooth muscle of rabbit duodenum, but they did not modify the frequency. Bay K8644 (L-type Ca2+ channel activator), apamin, charybdotoxin, and tetraetylammonium (K+ channel blockers) reverted the inhibition of amplitude of spontaneous contractions induced by genistein in longitudinal and circular smooth muscle. H-89 (protein kinase A inhibitor) antagonized the reduction of the amplitude of spontaneous contractions induced by quercetin in longitudinal and circular smooth muscle of duodenum, while 2,5-dideoxiadenosine (adenylyl cyclase inhibitor) reverted only the reduction of the amplitude in circular smooth muscle. In conclusion, genistein and quercetin reduce the spontaneous contractions in the duodenum by different mechanisms of actions. The effect of genistein would be mediated by Ca2+ and K+ channels, while the effect of quercetin would be mediated by cAMP and protein kinase A. PMID:26140633

  1. 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

  2. Ochratoxin-induced toxicity, oxidative stress and apoptosis ameliorated by quercetin--modulation by Nrf2.

    PubMed

    Ramyaa, Periasamy; Padma, Viswanadha Vijaya

    2013-12-01

    Ochratoxin (OTA) is one of the most abundant food contaminating mycotoxins and is commonly present in the food chain. Many of the effects associated with OTA, appear to be mediated through oxidative stress. Although the toxicity of OTA is fairly well characterized, antidotes for alleviating the toxicity are sparsely reported. Dietary antioxidants have gained much importance in the recent years for their antioxidative and therapeutic properties. In the present study the therapeutic strategy was directed towards use of quercetin, a dietary antioxidant to combat OTA-induced toxicity in Vero cell line. Our results demonstrate that quercetin pre-treatment suppressed OTA-induced cytotoxicity and oxidative stress. It modulated OTA-induced alteration on the antioxidant defence through activation of Nrf2 pathway. Morphological studies by scanning electron microscopy (SEM) and cell cycle analysis indicated that quercetin prevented OTA-induced apoptosis. It also inhibited the activation of caspase cascade that leads to DNA fragmentation. Quercetin also exhibited antigenotoxic potential by attenuating OTA-induced DNA damage and micronucleus (MN) formation. The results of the study demonstrate for the first time that quercetin pre-treatment prevents OTA-induced oxidative stress and apoptosis in Vero cell line. PMID:23994659

  3. 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

  4. Quercetin Impacts Expression of Metabolism- and Obesity-Associated Genes in SGBS Adipocytes

    PubMed Central

    Leiherer, Andreas; Stoemmer, Kathrin; Muendlein, Axel; Saely, Christoph H.; Kinz, Elena; Brandtner, Eva M.; Fraunberger, Peter; Drexel, Heinz

    2016-01-01

    Obesity is characterized by the rapid expansion of visceral adipose tissue, resulting in a hypoxic environment in adipose tissue which leads to a profound change of gene expression in adipocytes. As a consequence, there is a dysregulation of metabolism and adipokine secretion in adipose tissue leading to the development of systemic inflammation and finally resulting in the onset of metabolic diseases. The flavonoid quercetin as well as other secondary plant metabolites also referred to as phytochemicals have anti-oxidant, anti-inflammatory, and anti-diabetic effects known to be protective in view of obesity-related-diseases. Nevertheless, its underlying molecular mechanism is still obscure and thus the focus of this study was to explore the influence of quercetin on human SGBS (Simpson Golabi Behmel Syndrome) adipocytes’ gene expression. We revealed for the first time that quercetin significantly changed expression of adipokine (Angptl4, adipsin, irisin and PAI-1) and glycolysis-involved (ENO2, PFKP and PFKFB4) genes, and that this effect not only antagonized but in part even overcompensated the effect mediated by hypoxia in adipocytes. Thus, these results are explained by the recently proposed hypothesis that the protective effect of quercetin is not solely due to its free radical-scavenging activity but also to a direct effect on mitochondrial processes, and they demonstrate that quercetin might have the potential to counteract the development of obesity-associated complications. PMID:27187453

  5. Novel quercetin-3-O-glucoside eicosapentaenoic acid ester ameliorates inflammation and hyperlipidemia.

    PubMed

    Sekhon-Loodu, Satvir; Ziaullah, Ziaullah; Rupasinghe, H P Vasantha; Wang, Yanwen; Kulka, Marianna; Shahidi, Fereidoon

    2015-08-01

    Quercetin, a major flavonol, present abundantly in apples and onions, is widely studied for ameliorating metabolic syndrome abnormalities. However, quercetin is mainly present in plant food in the form of quercetin glycosides and has been reported for poor gastrointestinal absorption. The present study was designed with the purpose of imparting a lipophilic property to quercetin-3-O-glucoside (QG) by its acylation with eicosapentaenoic acid (EPA) and to study the influence of eicosapentaenoic acid ester of quercetin-3-O-glucoside (QE) on hyperlipidemia and inflammation in vivo and in vitro. QE was more effective in reducing the production of tumor necrosis factor-alpha (TNF-α), prostaglandin 2 (PGE2), cyclo-oxygenase (COX)-2 levels and nuclear expression of nuclear factor-kappa B (NF-кB) compared to the parent compounds (QG and EPA) and commercial drugs, after lipopolysaccharides (LPS) induced inflammation in THP-1 derived macrophages. Serum high-density lipoprotein (HDL)-cholesterol was significantly higher and hepatic total cholesterol concentration was lower in the rats fed high-fat diet supplemented with QE, compared to the high-fat diet with inflammation (HFL). The serum concentrations of C-reactive protein (CRP), interleukin (IL)-6, and interferon-gamma (IFN-γ) were significantly lower in QE treatment group than HFL group. EPA conjugated flavonol, QE, had significant anti-inflammatory and hypolipidemic properties and may be effective for the treatment of obesity-related disorders. PMID:26165697

  6. 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

  7. Assessment of anti-cytogenotoxic effects of quercetin in animals treated with topotecan.

    PubMed

    Bakheet, Saleh A

    2011-01-01

    The present investigation was directed to study the possible chemoprotective activity of orally administered quercetin against topotecan-induced cyto- and genotoxicity towards mouse somatic cells in vivo. DNA strand breaks, micronuclei formation, and mitotic activity were undertaken in the current study as markers of cyto- and genotoxicity. Oxidative stress markers such as intracellular reactive oxygen species generation, lipid peroxidation, and reduced and oxidized glutathione were assessed in bone marrow as a possible mechanism underlying this amelioration. Quercetin was neither cytotoxic nor genotoxic in mice at doses tested. Pretreatment of mice with quercetin significantly reduced topotecan-induced genotoxicity and cytotoxicity in bone marrow cells, and these effects were dose dependent. Moreover, prior administration of quercetin ahead of topotecan challenge ameliorated oxidative stress markers. In conclusion, quercetin has a protective role in the abatement of topotecan-induced cyto- and genotoxicity in the bone marrow cells of mice that resides, at least in part, on its antioxidant effects. Based on the data presented, strategies can be developed to decrease the topotecan-induced bone marrow suppression and secondary malignancy in cancer patients and medical personnel exposing to topotecan. PMID:21904648

  8. 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

  9. Redox reactions obtained by gamma irradiation of quercetin methanol solution are similar to in vivo metabolism.

    PubMed

    Marfak, A; Trouillas, P; Allais, D P; Calliste, C A; Duroux, J L

    2003-02-01

    The flavonol quercetin is one of the most well-known antioxidant flavonoids. Its antioxidant potential has been studied extensively during the last 10 years, but little is known about the metabolites formed in vivo that lead to the formation of depside and small molecules such as benzoic acids. In this study, gamma irradiation of a quercetin methanol solution was used as a model of certain oxidative reactions that occur in vivo. Qercetin at concentrations ranging from 5 x 10(-5) M to 5 x 10(-3) M, was irradiated with gamma rays at doses of 2-14 kGy. Quercetin degradation was evaluated by HPLC analysis. The major radiolytic metabolite was identified as a depside by NMR and LC-MS. Formation of 3,4-dihydroxybenzoic acid was also observed. The presence of CH3O. formed during methanol radiolysis is invoked to explain depside formation. Transformation of the 8-methoxy substituted depside (Q1) to the 8-hydroxyl substituted depside (Q2) is discussed. The antioxidant properties of quercetin metabolites are evaluated according to their capacity to decrease the EPR DPPH signal and to inhibit superoxide radical formed by the enzymatic reaction (xanthine + xanthine oxidase). For both assays, the IC50 of Q2 is twice as high as that of quercetin. PMID:12537527

  10. 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

  11. 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

  12. Pharmacophore model of the quercetin binding site of the SIRT6 protein.

    PubMed

    Ravichandran, S; Singh, N; Donnelly, D; Migliore, M; Johnson, P; Fishwick, C; Luke, B T; Martin, B; Maudsley, S; Fugmann, S D; Moaddel, R

    2014-04-01

    SIRT6 is a histone deacetylase that has been proposed as a potential therapeutic target for metabolic disorders and the prevention of age-associated diseases. We have previously reported on the identification of quercetin and vitexin as SIRT6 inhibitors, and studied structurally related flavonoids including luteolin, kaempferol, apigenin and naringenin. It was determined that the SIRT6 protein remained active after immobilization and that a single frontal displacement could correctly predict the functional activity of the immobilized enzyme. The previous study generated a preliminary pharmacophore for the quercetin binding site on SIRT6, containing 3 hydrogen bond donors and one hydrogen bond acceptor. In this study, we have generated a refined pharmacophore with an additional twelve quercetin analogs. The resulting model had a positive linear behavior between the experimental elution time verses the fit values obtained from the model with a correlation coefficient of 0.8456. PMID:24491483

  13. Efficient regioselective acylation of quercetin using Rhizopus oryzae lipase and its potential as antioxidant.

    PubMed

    Kumar, Vinod; Jahan, Firdaus; Mahajan, Richi V; Saxena, Rajendra Kumar

    2016-10-01

    The present investigation describes the regioselective enzymatic acylation of quercetin with ferulic acid using Rhizopus oryzae lipase. Optimization of reaction parameters resulted in 93.2% yield of the ester synthesized using 750IU of lipase in cyclo-octane at a temperature of 45°C. The reaction was successfully carried out upto 25g scale. The ester synthesized was analyzed by (1)H Nuclear magnetic resonance spectroscopy. The ester synthesized (quercetin ferulate) showed higher antiradical activity as compared to ascorbic acid using the 2,2-diphenyl-1-picrylhydrazyl radical method. These results on enzyme-catalyzed acylation of quercetin might be used to prepare and scale-up other flavonoids derivatives. PMID:27372535

  14. Quercetin nanocomposite as novel anticancer therapeutic: improved efficiency and reduced toxicity.

    PubMed

    Cirillo, Giuseppe; Vittorio, Orazio; Hampel, Silke; Iemma, Francesca; Parchi, Paolo; Cecchini, Marco; Puoci, Francesco; Picci, Nevio

    2013-06-14

    A three-functional nanocomposite was prepared by radical polymerization of methacrylic acid around carbon nanotubes in the presence of Quercetin as biologically active molecule and proposed as new anticancer therapeutic. The so-obtained hybrid material was characterized by FT-IR, Raman, SEM, TEM analyses, while the functionalization degree of 2.33 mg of Quercetin per g of composite was assessed by Folin-Ciocalteu test. Antioxidant test (DPPH and ABTS) showed that the covalent coupling did not interfere with the antioxidant properties of the flavonoid, while the anticancer activity was greatly enhanced with a recorded IC50 value much lower than free Quercetin. Cell viability tests on healthy cells demonstrated no-toxicity of the conjugate. PMID:23602995

  15. Pharmacophore model of the quercetin binding site of the SIRT6 protein

    PubMed Central

    Ravichandran, S.; Singh, N.; Donnelly, D.; Migliore, M.; Johnson, P.; Fishwick, C.; Luke, Brian T.; Martin, B.; Maudsley, S.; Fugmann, S. D.; Moaddel, R.

    2014-01-01

    SIRT6 is a histone deacetylase that has been proposed as a potential therapeutic target for metabolic disorders and the prevention of age-associated diseases. We have previously reported on the identification of quercetin and vitexin as SIRT6 inhibitors, and studied structurally related flavonoids including luteolin, kaempferol, apigenin and naringenin. It was determined that the SIRT6 protein remained active after immobilization and that a single frontal displacement could correctly predict the functional activity of the immobilized enzyme. The previous study generated a preliminary pharmacophore for the quercetin binding site on SIRT6, containing 3 hydrogen bond donors and one hydrogen bond acceptor. In this study, we have generated a refined pharmacophore with an additional twelve quercetin analogs. The resulting model had a positive linear behavior between the experimental elution time verses the fit values obtained from the model with a correlation coefficient of 0.8456. PMID:24491483

  16. Relaxation behavior and nonlinear properties of thermally stable polymers based on glycidyl derivatives of quercetin

    NASA Astrophysics Data System (ADS)

    Mishurov, Dmytro; Voronkin, Andrii; Roshal, Alexander; Brovko, Oleksandr

    2016-07-01

    Cross-linked polymers on the basis of di-, tri and tetraglycidyl ethers of quercetin (3,3‧,4‧,5,7-pentahydroxyflavone) were synthesized, and then, poled in electrical field of corona discharge. Investigations of structural, thermal and optical parameters of the polymer films were carried out. It was found that the polymers obtained from di- and triglycidyl quercetin ethers had high values of macroscopic quadratic susceptibilities and substantial stability of nonlinear optical (NLO) properties after the poling. Tetraglycidyl ether of quercetin forms the polymer of lower quadratic susceptibility, which demonstrates noticeable relaxation process resulting in decrease of the NLO effect. It is supposed that the difference of the NLO properties is due to peculiarities of physical network of the polymers, namely to the ratio between numbers of hydrogen bonds formed by hydroxyl groups of chromophore fragments and by the ones of interfragmental parts of the polymeric chains.

  17. 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

  18. 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.

  19. Quercetin induces human colon cancer cells apoptosis by inhibiting the nuclear factor-kappa B Pathway

    PubMed Central

    Zhang, Xiang-An; Zhang, Shuangxi; Yin, Qing; Zhang, Jing

    2015-01-01

    Quercetin can inhibit the growth of cancer cells with the ability to act as chemopreventers. Its cancer-preventive effect has been attributed to various mechanisms, including the induction of cell-cycle arrest and/or apoptosis as well as the antioxidant functions. Nuclear factor kappa-B (NF-κB) is a signaling pathway that controls transcriptional activation of genes important for tight regulation of many cellular processes and is aberrantly expressed in many types of cancer. Inhibitors of NF-κB pathway have shown potential anti-tumor activities. However, it is not fully elucidated in colon cancer. In this study, we demonstrate that quercetin induces apoptosis in human colon cancer CACO-2 and SW-620 cells through inhibiting NF-κB pathway, as well as down-regulation of B-cell lymphoma 2 and up-regulation of Bax, thus providing basis for clinical application of quercetin in colon cancer cases. PMID:25829782

  20. 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

  1. 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

  2. Quercetin abrogates IL-6/STAT3 signaling and inhibits glioblastoma cell line growth and migration

    SciTech Connect

    Michaud-Levesque, Jonathan; Bousquet-Gagnon, Nathalie; Beliveau, Richard

    2012-05-01

    Evidence has suggested that STAT3 functions as an oncogene in gliomagenesis. As a consequence, changes in the inflammatory microenvironment are thought to promote tumor development. Regardless of its origin, cancer-related inflammation has many tumor-promoting effects, such as the promotion of cell cycle progression, cell proliferation, cell migration and cell survival. Given that IL-6, a major cancer-related inflammatory cytokine, regulates STAT3 activation and is upregulated in glioblastoma, we sought to investigate the inhibitory effects of the chemopreventive flavonoid quercetin on glioblastoma cell proliferation and migration triggered by IL-6, and to determine the underlying mechanisms of action. In this study, we show that quercetin is a potent inhibitor of the IL-6-induced STAT3 signaling pathway in T98G and U87 glioblastoma cells. Exposure to quercetin resulted in the reduction of GP130, JAK1 and STAT3 activation by IL-6, as well as a marked decrease of the proliferative and migratory properties of glioblastoma cells induced by IL-6. Interestingly, quercetin also modulated the expression of two target genes regulated by STAT3, i.e. cyclin D1 and matrix metalloproteinase-2 (MMP-2). Moreover, quercetin reduced the recruitment of STAT3 at the cyclin D1 promoter and inhibited Rb phosphorylation in the presence of IL-6. Overall, these results provide new insight into the role of quercetin as a blocker of the STAT3 activation pathway stimulated by IL-6, with a potential role in the prevention and treatment of glioblastoma.

  3. Quercetin inhibits a large panel of kinases implicated in cancer cell biology.

    PubMed

    Boly, Rainatou; Gras, Thierry; Lamkami, Touria; Guissou, Pierre; Serteyn, Didier; Kiss, Robert; Dubois, Jacques

    2011-03-01

    Flavonoids are polyphenolic secondary metabolites from plants that possess a common phenylbenzopyrone structure (C6-C3-C6). Depending upon variations in their heterocyclic C-ring, flavonoids are categorised into one of the following groups: flavones, flavonols, flavanones, flavanols, anthocyanidins, isoflavones or chalcones. Flavonols include, among others, the molecules quercetin, myricetin and kaempferol. The anticancer activity of flavonols was first attributed to their electron-donating ability, which comes from the presence of phenolic hydroxyl groups. However, an emerging view is that flavonoids, including quercetin, may also exert modulatory actions in cells by acting through the protein kinase and lipid kinase signalling pathways. Data from the current study showed that 2 μM quercetin, a low concentration that represents less than 10% of its IC50 growth-inhibitory concentration as calculated from the average of eight distinct cancer cell lines, decreased the activity of 16 kinases by more than 80%, including ABL1, Aurora-A, -B, -C, CLK1, FLT3, JAK3, MET, NEK4, NEK9, PAK3, PIM1, RET, FGF-R2, PDGF-Rα and -Rß. Many of these kinases are involved in the control of mitotic processes. Quantitative video microscopy analyses revealed that quercetin displayed strong anti-mitotic activity, leading to cell death. In conclusion, quercetin partly exerts its anticancer activity through the inhibition of the activity of a large set of kinases. Quercetin could be an interesting chemical scaffold from which to generate novel derivatives possessing various types of anti-kinase activities. PMID:21206969

  4. 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

  5. Antioxidant action and cytotoxicity on HeLa and NIH-3T3 cells of new quercetin derivatives

    PubMed Central

    Veverka, Miroslav; Šturdík, Ernest; Jantová, Soňa

    2013-01-01

    Quercetin is a natural polyphenol with proven health beneficial activities. In this study 15 new quercetin derivatives were prepared with the aim to enhance their bioavailability. Modification of their physicochemical properties could herewith improve the action in cells. The prepared compounds were tested for their antioxidant and cytotoxic activity. The ability to scavenge free radicals as well as ferric reducing antioxidant power of the new derivatives was not better than that of unmodified quercetin. But for acetylated esters a better cytotoxic activity was found on human cervical cancer cells HeLa than for the initial molecule. The best effect revealed chloronaphtoquinone quercetin (IC50=13.2 µM). For this compound comparable cytotoxic action on non-cancer murine fibroblast cells was detected (IC50=16.5 µM). The obtained results indicate that appropriate lipophilization of the quercetin molecule could improve its cytotoxic action in cells, probably due to its enhanced bioavailability. PMID:24678260

  6. Effect of quercetin against lindane induced alterations in the serum and hepatic tissue lipids in wistar rats

    PubMed Central

    Padma, Viswanadha Vijaya; Lalitha, Gurusamy; Shirony, Nicholson Puthanveedu; Baskaran, Rathinasamy

    2012-01-01

    Objective To assess the effect of quercetin (flavonoid) against lindane induced alterations in lipid profile of wistar rats. Methods Rats were administered orally with lindane (100 mg/kg body weight) and quercetin (10 mg/kg body weight) for 30 days. After the end of treatment period lipid profile was estimated in serum and tissue. Results Elevated levels of serum cholesterol, triglycerides, low density lipoprotein (LDL), very Low Density Lipoprotein (VLDL) and tissue triglycerides, cholesterol with concomitant decrease in serum HDL and tissue phospholipids were decreased in lindane treated rats were found to be significantly decreased in the quercetin and lindane co-treated rats. Conclusions Our study suggests that quercetin has hypolipidemic effect and offers protection against lindane induced toxicity in liver by restoring the altered levels of lipids. The quercetin cotreatment along with lindane for 30 days reversed these biochemical alterations in lipids induced by lindane. PMID:23569870

  7. Response of keloid fibroblasts to Vitamin D3 and quercetin treatment - in vitro study.

    PubMed

    Mathangi Ramakrishnan, K; Babu, M; Lakshmi Madhavi, M S

    2015-09-30

    Keloid scars continue to pose a challenge to clinicians as the treatment armamentarium lacks a formidable agent to tackle them. We have undertaken an in vitro study based on the mechanism of action of Vitamin D3 and quercetin on isolated keloid fibroblasts. Dose-dependent action on the reduction of cellular proliferation, collagen synthesis and induction of apoptosis by Vitamin D3 and quercetin are analyzed and probable mechanism of action is elaborated. This study thus opens up newer avenues in tackling keloid scars effectively. PMID:27279805

  8. Urine recovery experiments with quercetin and other mutagens using the Ames test

    SciTech Connect

    Busch, D.B.; Hatcher, J.F.; Bryan, G.T.

    1986-01-01

    Recovery from urine of the mutagenic activity of 2-anthramine, cyclophosphamide, 7,12-dimethylbenz(a)anthracene, 6-chloro-9-((3-(2-chloroethylamino)-propyl)amino)-2-methoxyacridine dihydrochloride (ICR-191), mitomycin-C, nitrofurantoin, and quercetin was studied with several of the Ames tester strains using acetone-extracted XAD-2 columns with yields ranging from 27% to 79%. Dose responses of the pure chemicals were also studied, and results showed TA 97 to be far more susceptible to quercetin mutagenesis than TA 1537. Reducing pour plate agar volume enhanced mutagenesis.

  9. Quercetin Supplementation Attenuates the Progression of Cancer Cachexia in ApcMin/+ Mice123

    PubMed Central

    Velázquez, Kandy T.; Enos, Reilly T.; Narsale, Aditi A.; Puppa, Melissa J.; Davis, J. Mark; Murphy, E. Angela; Carson, James A.

    2014-01-01

    Although there are currently no approved treatments for cancer cachexia, there is an intensified interest in developing therapies because of the high mortality index associated with muscle wasting diseases. Successful treatment of the cachectic patient focuses on improving or maintaining body weight and musculoskeletal function. Nutraceutical compounds, including the natural phytochemical quercetin, are being examined as potential treatments because of their anti-inflammatory, antioxidant, and anticarcinogenic properties. The purpose of this study was to determine the effect of quercetin supplementation on the progression of cachexia in the adenomatous polyposis coli (Apc)Min/+ mouse model of colorectal cancer. At 15 wk of age, C57BL/6 and male ApcMin/+ mice were supplemented with 25 mg/kg of quercetin or vehicle solution mix of Tang juice and water (V) daily for 3 wk. Body weight, strength, neuromuscular performance, and fatigue were assessed before and after quercetin or V interventions. Indicators of metabolic dysfunction and inflammatory signaling were also assessed. During the treatment period, the relative decrease in body weight in the ApcMin/+ mice gavaged with V (ApcMin/+V; −14% ± 2.3) was higher than in control mice gavaged with V (+0.6% ± 1.0), control mice gavaged with quercetin (−2% ± 1.0), and ApcMin/+ mice gavaged with quercetin (ApcMin/+Q; −9% ± 1.3). At 18 wk of age, the loss of grip strength and muscle mass shown in ApcMin/+V mice was significantly attenuated (P < 0.05) in ApcMin/+Q mice. Furthermore, ApcMin/+V mice had an induction of plasma interleukin-6 and muscle signal transducer and activator of transcription 3 phosphorylation, which were significantly (P < 0.05) mitigated in ApcMin/+Q mice, despite having a similar tumor burden. Quercetin treatment did not improve treadmill run-time-to-fatigue, hyperglycemia, or hyperlipidemia in cachectic ApcMin/+ mice. Overall, quercetin supplementation positively affected several aspects of

  10. Response of keloid fibroblasts to Vitamin D3 and quercetin treatment - in vitro study

    PubMed Central

    Mathangi Ramakrishnan, K.; Babu, M.; Lakshmi Madhavi, M.S.

    2015-01-01

    Summary Keloid scars continue to pose a challenge to clinicians as the treatment armamentarium lacks a formidable agent to tackle them. We have undertaken an in vitro study based on the mechanism of action of Vitamin D3 and quercetin on isolated keloid fibroblasts. Dose-dependent action on the reduction of cellular proliferation, collagen synthesis and induction of apoptosis by Vitamin D3 and quercetin are analyzed and probable mechanism of action is elaborated. This study thus opens up newer avenues in tackling keloid scars effectively. PMID:27279805

  11. 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

  12. 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.

  13. Synthesis, characterization and investigation of antioxidant activity of cobalt quercetin complex

    NASA Astrophysics Data System (ADS)

    Birjees Bukhari, S.; Memon, Shahabuddin; Mahroof Tahir, M.; Bhanger, M. I.

    2008-12-01

    This article describes a novel synthesis of cobalt and quercetin·2H 2O complex in methanol, characterized by using elemental analysis, UV-visible, 1H NMR, TGA, DSC and IR spectrometric techniques. The formation of complex is deduced from the UV-visible spectra which shows that the successive formation of cobalt-quercetin complex occurs in a ratio of 2:1 (metal/ligand) stoichiometrically. The antioxidant activity of the complex was evaluated by using 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging method. In this work, we have shown that the metal complexed flavonoids are much more effective free radical scavengers than the free flavonoids.

  14. 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

  15. 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.

  16. 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

  17. Ameliorative effect of quercetin against arsenic-induced sperm DNA damage and daily sperm production in adult male rats.

    PubMed

    Jahan, Sarwat; Rehman, Saima; Ullah, Hizb; Munawar, Asma; Ain, Qurat Ul; Iqbal, Tariq

    2016-07-01

    In this study, the protective effect of quercetin was evaluated against arsenic induced reproductive ailments in male rats. For this purpose, male rats (n = 5/group) weighing 180-250 g were used. First group served as control, second group received arsenic (50 ppm) in drinking water. Third group was treated with quercetin (50 mg/kg) alone, while fourth group received arsenic + quercetin. All treatments were carried out for 49 days. After treatment, animals were killed by decapitation; testis and epididymis were dissected out. Right epididymis was minced immediately for comet assay, while left epididymis was processed for histology. Similarly, right testis was homogenized for estimation of daily sperm production (DSP) and detection of metal concentration. The results of our research revealed that arsenic treatment did not cause any significant change in body weight and testicular volume. Quercetin treatment significantly prevented tissue deposition of arsenic within the testis. Arsenic treatment caused a significant reduction in DSP, however, in the arsenic + quercetin-treated group and quercetin alone-treated group, DSP was significantly high as compared to the arsenic-treated group. Histological study of epididymis showed empty lumen in arsenic-treated group while in arsenic + quercetin-treated group and quercetin alone-treated group, lumen were filled with sperm and were comparable to control. Sperm DNA damage, induced by arsenic, was significantly reversed toward control levels by supplementation of quercetin. These results suggest that quercetin not only prevents deposition of arsenic in tissues, but can also protect the sperm DNA damage. PMID:26524343

  18. Optimization of process parameters of extraction of amentoflavone, quercetin and ginkgetin from Taxus chinensis using supercritical CO2 plus co-solvent.

    PubMed

    Ruan, Xiao; Yan, Liu-Ye; Li, Xian-Xian; Liu, Ben; Zhang, Huan; Wang, Qiang

    2014-01-01

    The effects of extraction time, temperature, pressure and different concentration of ethanol and their interactions on the yields of amentoflavone, quercetin and ginkgetin extracted from Taxus chinensis by supercritical CO2 were investigated by using a central composite design (CCD). An CCD experimental design with four factors and five levels was used to optimize the extraction parameters. Ultra performance liquid chromatography (UPLC) was used to analyze the content of the tree components in the extracts. Experimental results show that the main effects of factors and their interactions are significant on the yields (p < 0.05). The optimal extraction conditions were established for the three compounds: yield of 4.47 mg/g for amentoflavone at 48 °C, 25 MPa, 2.02 h and 78.5% ethanol, 3.73 mg/g for quercetin at 46 °C, 24 MPa, 2.3 h, 82% ethanol and 3.47 mg/g for ginkgetin at 48 °C, 20 MPa, 2.38 h, 82% ethanol, respectively. PMID:25365294

  19. Hyperglycemia and anthocyanin inhibit quercetin metabolism in HepG2 cells

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A high glucose (Glu) milieu promotes generation of reactive oxygen species, which may not only cause cellular damage, but also modulate phase II enzymes that are responsible for the metabolism of flavonoids. Thus, we examined the effect of a high Glu milieu on quercetin (Q) metabolism in HepG2 cells...

  20. 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

  1. Rutin, quercetin, and free amino acid analysis in buckwheat (Fagopyrum) seeds from different locations.

    PubMed

    Bai, C Z; Feng, M L; Hao, X L; Zhong, Q M; Tong, L G; Wang, Z H

    2015-01-01

    In this study, five common buckwheats and nine tartary buckwheats grown at different locations were analyzed for the contents of rutin, quercetin, and amino acids by high-performance liquid chromatography and spectrophotometry. The rutin content was higher than quercetin in buckwheat seeds. Rutin content was in the range from 0.05 (0.05 g per 100 g dry seeds) to 1.35% of buckwheat seeds. Quercetin content varied from 0.01 to 0.17% and in some common buckwheats it was even difficult to detect. Comparatively, tartary buckwheat seeds contained more rutin and quercetin than common buckwheat seeds. Meanwhile, the bran has higher rutin content than the farina in tartary buckwheat seeds, with a respective content of 0.45 to 1.19% and 0.14 to 0.67%. It was found that amino acid contents were around 1.79 to 12.65% (farina) and 5.74 to 7.89% (bran) in common buckwheats, and 1.73 to 5.63% (farina) and 2.64 to 16.78% (bran) in tartary buckwheat seeds. The highest total rutin content was found to be 1.35% in tartary buckwheat seeds from Sichuan, China. The highest total amounts of amino acid were detected to be 20.13% in tartary buckwheat seeds from Changzhi, Shanxi Province (China). Our results suggested that food products made of whole-buckwheat flour are healthier than those made of fine white flour. PMID:26782554

  2. 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...

  3. Quercetin declines plasma exposure of metoprolol tartrate in the rat model

    PubMed Central

    Challa, Siva R.; Challa, Venkatesh R.; Ragam, Satheesh K.

    2014-01-01

    The study was undertaken to evaluate the effect of quercetin on the pharmacokinetics of Metoprolol tartrate. A single dose in vivo pharmacokinetic study was carried out in rat models. In this study, rats were treated with quercetin (10 mg/kg) and metoprolol tartrate (20 mg/kg) orally and blood samples were collected 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 8, 12 h post treatment. Plasma concentration of metoprolol tartrate was estimated using reverse phase-high-performance liquid chromatography method. Area under the plasma concentration-time curve (AUC0-12) of metoprolol has significantly (P < 0.001) decreased by 9.8 times in the metoprolol and quercetin combination group (9434.65 ± 3525.02) when compared with AUC0-12 metoprolol of metoprolol-alone treated group (962.17 ± 242.81). AUC0-∞ of metoprolol has significantly (P < 0.001) decreased by 14.9 times in the combination group (16670.79 ± 12129.06) in comparison to AUC0-∞ of metoprolol of metoprolol-alone treated group (1113.68 ± 441.83). the results obtained herein indicate that quercetin remarkably declines the plasma exposure of metoprolol when concomitantly administered by oral route. PMID:25364697

  4. Quercetin inhibits the migration and proliferation of astrocytes in wound healing.

    PubMed

    Yuan, Zhaohu; Yao, Fang; Hu, Ziyou; Sun, Shumei; Wu, Bingyi

    2015-05-01

    A previous study showed that quercetin inhibits astrogliosis in a scratch-wound model, but did not identify the underlying mechanisms. Here, we show that quercetin exerts no effect on apoptosis or the viability of astrocytes, but significantly inhibits their proliferation, arresting them in the G1 phase and decreasing the percentage of cells in the S and G2 phase. In addition, we found that quercetin significantly decreased the phosphorylation of ERK1/2 and FAK, a downstream ERK signaling protein. Inhibition of this pathway with U0126, an inhibitor of MAP kinase, retarded wound closure, whereas sustained p-ERK1/2 activation, induced by vanadate, restored astrocyte migration. Our findings thus indicate that quercetin inhibits healing in the scratch-wound model of primary astrocytes in two ways: blockade of the G1 to S phase cell cycle transition and inhibition of the ERK/FAK signaling pathway, which may contribute toward decreasing astroglial scar formation in vivo. PMID:25793633

  5. 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

  6. Myricetin and quercetin attenuate ischemic injury in glial cultures by different mechanisms

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We have demonstrated that polyphenols from cinnamon and green tea reduce cell swelling and mitochondrial dysfunction in C6 glial cultures following ischemic injury. We tested the protective effects of the flavonoid polyphenols, myricetin and quercetin, on key features of ischemic injury. C6 cultures...

  7. Preparation and characterization of lipid based nanosystems for topical delivery of quercetin.

    PubMed

    Bose, Sonali; Michniak-Kohn, Bozena

    2013-02-14

    The main objective of this study was to evaluate the potential of lipid nanosystems for topical delivery of the naturally occurring flavonoid quercetin. These lipid based nanosystems were manufactured using a solvent free probe ultrasonication process. Formulation factors such as the nature of the lipid (solid/combination of solid and liquid) in solid lipid nanoparticle (SLN) and nanostructured lipid carrier (NLC) systems and drug loading were evaluated to produce an optimum formulation with adequate physical stability for up to 14 weeks at 2-8°C. The mean particle size of the optimized formulation was around 282 nm, with a zeta potential value of -36.57 ± 2.67 mV, indicating the formation of a stable system. Release studies showed a biphasic release profile, characterized by an initial burst release followed by a more controlled release pattern from both SLN and NLC systems. The NLC system showed the highest improvement in topical delivery of quercetin manifested by the amount of quercetin retained in full thickness human skin, compared to a control formulation with similar composition and particle size in the micrometer range. This study demonstrated the feasibility of nanostructured lipid carrier systems for improved topical delivery of quercetin. PMID:23246734

  8. Improvement in safety and cycle life of lithium-ion batteries by employing quercetin as an electrolyte additive

    NASA Astrophysics Data System (ADS)

    Lee, Meng-Lun; Li, Yu-Han; Yeh, Jien-Wei; Shih, Han C.

    2012-09-01

    Quercetin, an organic antioxidant, has been employed as an additive in lithium-ion cells to enhance the electrochemical performance to enhance the cycle life and the overcharging characteristics of LiPF6/EC + EMC + DMC (1 M) when used as an electrolyte. A LiCoO2/graphite full cell with 0.05% quercetin showed a significant improvement in safety associated with overcharging tolerance and thermal stability, without causing damage in C-rate capability, and even a small improvement in cycle life performance. The quercetin-containing lithium battery showed an improvement in its electrochemical properties with 92% capacity retention after 350 cycles from 2.8 to 4.3 V, at a rate of 1 C; compared to 85% capacity retention for a cell without quercetin operated under the same conditions. The electrochemical impedance spectroscopy (EIS) results for the LiCoO2 cathode show that the addition of 0.05% quercetin provides a significant suppression in the impedance of the cell after 60 cycles. The improvement might result from the formation of a passivation microstructure (from quercetin oxidation) on the electrode's surface. The quercetin-containing batteries provided long term cycling and a high safety performance, making them a viable power source for applications involving electric devices with significant safety requirements.

  9. 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.

  10. Effectiveness of Periodic Treatment of Quercetin against Influenza A Virus H1N1 through Modulation of Protein Expression.

    PubMed

    Vaidya, Bipin; Cho, Se-Young; Oh, Kyung-Seo; Kim, Song Hak; Kim, Yeong O; Jeong, Eun-Hye; Nguyen, Thoa Thi; Kim, Sung Hyun; Kim, In Seon; Kwon, Joseph; Kim, Duwoon

    2016-06-01

    Kimchi, a traditional fermented food regularly consumed in Korea, contains various types of antimicrobial compounds. Among the tested compounds present in common spices used in Kimchi, quercetin showed the highest selectivity index against influenza A virus (IAV) H1N1. In this study, the effect of pretreatment and periodic treatment with quercetin against IAV in Madin-Darby canine kidney cells was observed. Compared to pretreatment, periodic treatment resulted in significantly higher cell viability but lower relative expression of the IAV PA gene and total apoptosis and cell death. To explain the mechanisms underlying the antiviral effects of quercetin treatment, a comparative proteomic analysis was performed in four samples (mock, quercetin-treated, IAV-infected, and quercetin-treated IAV-infected). Among the 220 proteins, 56 proteins were classified nonhierarchically into three clusters and were differentially modulated by quercetin treatment in IAV-infected cells. Post-translational modifications were identified in 68 proteins. In conclusion, periodic treatment with quercetin is effective in reducing IAV infection, and differentially regulates the expression of key proteins, including heat shock proteins, fibronectin 1, and prohibitin to reduce IAV replication. PMID:27157719

  11. 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

  12. Quercetin Inhibits Fibroblast Activation and Kidney Fibrosis Involving the Suppression of Mammalian Target of Rapamycin and β-catenin Signaling

    PubMed Central

    Ren, Jiafa; Li, Jianzhong; Liu, Xin; Feng, Ye; Gui, Yuan; Yang, Junwei; He, Weichun; Dai, Chunsun

    2016-01-01

    Quercetin, a flavonoid found in a wide variety of plants and presented in human diet, displays promising potential in preventing kidney fibroblast activation. However, whether quercetin can ameliorate kidney fibrosis in mice with obstructive nephropathy and the underlying mechanisms remain to be further elucidated. In this study, we found that administration of quercetin could largely ameliorate kidney interstitial fibrosis and macrophage accumulation in the kidneys with obstructive nephropathy. MTORC1, mTORC2, β-catenin as well as Smad signaling were activated in the obstructive kidneys, whereas quercetin could markedly reduce their abundance except Smad3 phosphorylation. In cultured NRK-49F cells, quercetin could inhibit α-SMA and fibronectin (FN) expression induced by TGFβ1 treatment. MTORC1, mTORC2, β-catenin and Smad signaling pathways were stimulated by TGFβ1 at a time dependent manner. Similar to those findings in the obstructive kidneys, mTORC1, mTORC2 and β-catenin, but not Smad signaling pathways were remarkably blocked by quercetin treatment. Together, these results suggest that quercetin inhibits fibroblast activation and kidney fibrosis involving a combined inhibition of mTOR and β-catenin signaling transduction, which may act as a therapeutic candidate for patients with chronic kidney diseases. PMID:27052477

  13. 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

  14. Quercetin sensitizes pancreatic cancer cells to TRAIL-induced apoptosis through JNK-mediated cFLIP turnover.

    PubMed

    Kim, Ji Hye; Kim, Min Joo; Choi, Kyung-Chul; Son, Jaekyoung

    2016-09-01

    Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent that can selectively kill cancer cells. Nonetheless, many cancers are resistant to TRAIL, and the molecular mechanisms of TRAIL resistance in cancer, particularly pancreatic cancer, are still unclear. In this study, we tested the hypothesis that quercetin, a flavonoid, induces apoptosis in TRAIL-resistant pancreatic cancer cells. Although quercetin alone had no significant cytotoxic effect, when combined with TRAIL, it promoted TRAIL-induced apoptosis that required mitochondrial outer membrane permeabilization. A BH3-only protein BID knockdown dramatically attenuated TRAIL/quercetin-induced apoptosis. The expression levels of cellular FLICE-like inhibitory protein (cFLIP) decreased in a dose-dependent manner in the presence of quercetin, and overexpression of cFLIP was able to robustly rescue pancreatic cancer cells from TRAIL/quercetin-induced apoptosis. Additionally, quercetin activated c-Jun N-terminal kinase (JNK) in a dose-dependent manner, which in turn induced the proteasomal degradation of cFLIP, and JNK activation also sensitized pancreatic cancer cells to TRAIL-induced apoptosis. Thus, our results suggest that quercetin induces TRAIL-induced apoptosis via JNK activation-mediated cFLIP turnover. PMID:27477310

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  1. Metabolic faecal fingerprinting of trans-resveratrol and quercetin following a high-fat sucrose dietary model using liquid chromatography coupled to high-resolution mass spectrometry.

    PubMed

    Etxeberria, Usune; Arias, Noemi; Boqué, Noemí; Romo-Hualde, Ana; Macarulla, M Teresa; Portillo, María P; Milagro, Fermín I; Martínez, J Alfredo

    2015-08-01

    Faecal non-targeted metabolomics deciphers metabolic end-products resulting from the interactions among food, host genetics, and gut microbiota. Faeces from Wistar rats fed a high-fat sucrose (HFS) diet supplemented with trans-resveratrol and quercetin (separately or combined) were analysed by liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS). Metabolomics in faeces are categorised into four clusters based on the type of treatment. Tentative identification of significantly differing metabolites highlighted the presence of carbohydrate derivatives or conjugates (3-phenylpropyl glucosinolate and dTDP-D-mycaminose) in the quercetin group. The trans-resveratrol group was differentiated by compounds related to nucleotides (uridine monophosphate and 2,4-dioxotetrahydropyrimidine D-ribonucleotide). Marked associations between bacterial species (Clostridium genus) and the amount of some metabolites were identified. Moreover, trans-resveratrol and resveratrol-derived microbial metabolites (dihydroresveratrol and lunularin) were also identified. Accordingly, this study confirms the usefulness of omics-based techniques to discriminate individuals depending on the physiological effect of food constituents and represents an interesting tool to assess the impact of future personalized therapies. PMID:26156396

  2. N-Butyl-4-butyl­imino-2-methyl­pentan-2-aminium (E)-quercetinate

    PubMed Central

    Grosu, Ioana-Georgeta; Borodi, Gheorghe; Pop, Mihaela Maria

    2012-01-01

    The title salt, C14H31N2 +·C15H9O7 −, was obtained in the reaction of quercetin with n-butyl­amine in a mixture of acetone and hexane. The crystal structure determination shows that the quercetin donates one of its phenol H atoms to the N-butyl-4-butyl­imino-2-methyl­pentan-2-amine mol­ecule. The crystal structure of the salt is stabilized by intramolecular (N—H⋯N for the cation and O—H⋯O for the anion) and intermolecular hydrogen bonding (N—H⋯O between cation–anion pairs and O—H⋯O between anions). Quercetin molecules form dimers connected into a two-dimensional network. The dihedral angle between the quercetin ring systems is 19.61 (8)°. PMID:22904895

  3. 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

  4. 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

  5. Protective effects of quercetin on cadmium fluoride induced oxidative stress at different intervals of time in mouse liver.

    PubMed

    Zargar, Seema; Siddiqi, Nikhat Jamal; Al Daihan, Sooad Khalaf; Wani, Tanveer A

    2015-01-01

    Quercetin, a member of the flavonoid family is a major antioxidant acquired in humans by food consumption, while Cadmium fluoride (CdF2) is one of the naturally occurring chemicals having adverse effects. The protective effect of quercetin on time dependent oxidative damage induced in mice liver by CdF2 was studied in the following groups of mice consisting of six mice each: (i) control group; (ii) mice treated with single i.p injection of 2 mg/kg bw CdF2 for 24 h; (iii) mice treated with single i.p injection of 2 mg/kg bw CdF2 for 48 h; (iv) mice treated with single i.p injection of quercetin (100 mg/kg bw); (v) mice treated with i.p injection of 100 mg/kg bw of quercetin followed by i.p injection of CdF2 (2 mg/kg bw) for 24 h; and (vi) mice treated with i.p injection of 100mg/kg bw of quercetin followed by CdF2 (2 mg/kg bw) for 48 h. Administration of quercetin two hours before CdF2 significantly reduced the biochemical alterations in reduced glutathione, ascorbic acid, lipid peroxidation, super oxide dismutase, catalase and total protein (p<0.05). Histopathology also showed the protective effect of quercetin. The livers treated with CdF2 were atrophic, markedly nodular, inflamed and necrotic. However, this effect was reduced to a minimum in the mice pre-treated for two hours with quercetin. PMID:25856559

  6. 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

  7. A combination of methylprednisolone and quercetin is effective for the treatment of cardiac contusion following blunt chest trauma in rats

    PubMed Central

    Demir, F.; Güzel, A.; Katı, C.; Karadeniz, C.; Akdemir, U.; Okuyucu, A.; Gacar, A.; Özdemir, S.; Güvenç, T.

    2014-01-01

    Cardiac contusion is a potentially fatal complication of blunt chest trauma. The effects of a combination of quercetin and methylprednisolone against trauma-induced cardiac contusion were studied. Thirty-five female Sprague-Dawley rats were divided into five groups (n=7) as follows: sham, cardiac contusion with no therapy, treated with methylprednisolone (30 mg/kg on the first day, and 3 mg/kg on the following days), treated with quercetin (50 mg·kg−1·day−1), and treated with a combination of methylprednisolone and quercetin. Serum troponin I (Tn-I) and tumor necrosis factor-alpha (TNF-α) levels and cardiac histopathological findings were evaluated. Tn-I and TNF-α levels were elevated after contusion (P=0.001 and P=0.001). Seven days later, Tn-I and TNF-α levels decreased in the rats treated with methylprednisolone, quercetin, and the combination of methylprednisolone and quercetin compared to the rats without therapy, but a statistical significance was found only with the combination therapy (P=0.001 and P=0.011, respectively). Histopathological degeneration and necrosis scores were statistically lower in the methylprednisolone and quercetin combination group compared to the group treated only with methylprednisolone (P=0.017 and P=0.007, respectively). However, only degeneration scores were lower in the combination therapy group compared to the group treated only with quercetin (P=0.017). Inducible nitric oxide synthase positivity scores were decreased in all treatment groups compared to the untreated groups (P=0.097, P=0.026, and P=0.004, respectively). We conclude that a combination of quercetin and methylprednisolone can be used for the specific treatment of cardiac contusion. PMID:25098616

  8. 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

  9. 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

  10. 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

  11. Improvement of memory recall by quercetin in rodent contextual fear conditioning and human early-stage Alzheimer's disease patients.

    PubMed

    Nakagawa, Toshiyuki; Itoh, Masanori; Ohta, Kazunori; Hayashi, Yuichi; Hayakawa, Miki; Yamada, Yasushi; Akanabe, Hiroshi; Chikaishi, Tokio; Nakagawa, Kiyomi; Itoh, Yoshinori; Muro, Takato; Yanagida, Daisuke; Nakabayashi, Ryo; Mori, Tetsuya; Saito, Kazuki; Ohzawa, Kaori; Suzuki, Chihiro; Li, Shimo; Ueda, Masashi; Wang, Miao-Xing; Nishida, Emika; Islam, Saiful; Tana; Kobori, Masuko; Inuzuka, Takashi

    2016-06-15

    Patients with Alzheimer's disease (AD) experience a wide array of cognitive deficits, which typically include the impairment of explicit memory. In previous studies, the authors reported that a flavonoid, quercetin, reduces the expression of ATF4 and delays memory deterioration in an early-stage AD mouse model. In the present study, the effects of long-term quercetin intake on memory recall were assessed using contextual fear conditioning in aged wild-type mice. In addition, the present study examined whether memory recall was affected by the intake of quercetin-rich onion (a new cultivar of hybrid onion 'Quergold') powder in early-stage AD patients. In-vivo analysis indicated that memory recall was enhanced in aged mice fed a quercetin-containing diet. Memory recall in early-stage AD patients, determined using the Revised Hasegawa Dementia Scale, was significantly improved by the intake of quercetin-rich onion (Quergold) powder for 4 weeks compared with the intake of control onion ('Mashiro' white onion) powder. These results indicate that quercetin might influence memory recall. PMID:27145228

  12. 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

  13. Beneficial effects of quercetin-iron complexes on serum and tissue lipids and redox status in obese rats.

    PubMed

    Imessaoudene, Asmahan; Merzouk, Hafida; Berroukeche, Farid; Mokhtari, Nassima; Bensenane, Bachir; Cherrak, Sabri; Merzouk, Sid Ahmed; Elhabiri, Mourad

    2016-03-01

    Obesity is characterized by iron deficiency, carbohydrate and fat alterations as well as oxidative stress. Iron status monitoring is recommended because of the conventional oral iron preparations that frequently exacerbate the already present oxidative stress. Iron complexation by natural antioxidants can be exploited. We herein investigated the metabolic effects of quercetin (25 mg/kg/day), iron (2.5 mg Fe/kg/day) or quercetin-iron complexes (molar ratio 5:1; 25 mg/2.5 mg/kg/day) in animal models of obesity. Our results emphasized that obese rats displayed metabolic alterations that were worsened by iron supplementation. In contrast, quercetin used alone or as iron complex clearly prevented adipose fat accumulation and alleviated the hyperglycemia, hyperlipidemia, liver steatosis and oxidative stress. In addition, it induced a modulation of lipase activities in obese rats. Interestingly, quercetin-iron complexes showed enhanced beneficial effects such as a corrected iron deficiency in obese rats when compared to quercetin alone. In conclusion, antianemic, hypoglycemic, hypolipidemic and antioxidative effects of the quercetin-iron complexes shed a light on their beneficial use against obesity-related metabolic alterations. PMID:26895671

  14. The pleiotropic flavonoid quercetin: from its metabolism to the inhibition of protein kinases in chronic lymphocytic leukemia.

    PubMed

    Russo, Gian Luigi; Russo, Maria; Spagnuolo, Carmela

    2014-10-01

    Quercetin is a flavonoid, of the subclass flavonols, possessing potential anticancer properties. It has often been defined as a functionally pleiotropic molecule because it can simultaneously target multiple pathways bypassing or ameliorating the onset of drug resistance in malignant cells. In this context, we reviewed the sometimes paradoxical antioxidant properties of quercetin and the functional role of its glucuronide and/or sulfate conjugates to discuss the low bioavailability of the molecule measured in vivo. We recently demonstrated that quercetin is able to sensitize several leukemia cell lines as well as B cells isolated from patients affected by chronic lymphocytic leukemia (CLL) to death ligand agonists (anti-CD95 and rTRAIL). The flavonol also potentiates the effect of canonical and innovative chemotherapeutic drugs (fludarabine and ABT-737) against CLL. The apoptosis-enhancing activity of quercetin in cell lines and B-CLL cells depends upon the modulated expression and activity of Mcl-1, an anti-apoptotic protein belonging to the Bcl-2 family. Herein, we suggest that the pleotropic activity of quercetin in CLL is obtained by the direct inhibition of key protein kinases, which positively regulate Mcl-1 activity and by indirect downregulation of Mcl-1 mRNA and protein levels acting on its mRNA stability and proteasome-mediated degradation. Finally, we highlighted the pros and cons of quercetin supplementation in cancer therapy and in prevention. PMID:25096193

  15. Neurite Outgrowth and Neuroprotective Effects of Quercetin from Caesalpinia mimosoides Lamk. on Cultured P19-Derived Neurons.

    PubMed

    Tangsaengvit, Napat; Kitphati, Worawan; Tadtong, Sarin; Bunyapraphatsara, Nuntavan; Nukoolkarn, Veena

    2013-01-01

    Quercetin has been isolated for the first time from ethyl acetate extract of Caesalpinia mimosoides Lamk. C. mimosoides Lamk. (Fabaceae) or Cha rueat (Thai name) is an indigenous plant found in mixed deciduous forest in northern and north-eastern parts of Thailand. Thai rural people consume its young shoots and leaves as a fresh vegetable, as well as it is used for medicinal purposes.The antioxidant capacity in terms of radical scavenging activity of quercetin was determined as IC50 of 3.18 ± 0.07 µg/mL, which was higher than that of Trolox and ascorbic acid (12.54 ± 0.89 and 10.52 ± 0.48 µg/mL, resp.). The suppressive effect of quercetin on both purified and cellular acetylcholinesterase (AChE) enzymes was investigated as IC50 56.84 ± 2.64 and 36.60 ± 2.78 µg/mL, respectively. In order to further investigate the protective ability of quercetin on neuronal cells, P19-derived neurons were used as a neuronal model in this study. As a result, quercetin at a very low dose of 1 nM enhanced survival and induced neurite outgrowth of P19-derived neurons. Furthermore, this flavonoid also possessed significant protection against oxidative stress induced by serum deprivation. Altogether, these findings suggest that quercetin is a multifunctional compound and promising valuable drugs candidate for the treatment of neurodegenerative disease. PMID:23840266

  16. Protective effects of quercetin and taraxasterol against H2O2-induced human umbilical vein endothelial cell injury in vitro

    PubMed Central

    YANG, DONGWEI; LIU, XINYE; LIU, MIN; CHI, HAO; LIU, JIRONG; HAN, HUAMIN

    2015-01-01

    Due to the association between inflammation and endothelial dysfunction in atherosclerosis, the blockage of the inflammatory process that occurs on the endothelial cells may be a useful way of preventing atherosclerosis. In the present study, human umbilical vein endothelial cells (HUVECs) were used to investigate the protective effects of quercetin and taraxasterol against H2O2-induced oxidative damage and inflammation. HUVECs were pretreated with quercetin or taraxasterol at concentrations ranging between 0 and 210 µM for 12 h, prior to being administered different concentrations of H2O2 for 4 h. Cell viability and levels of apoptosis were assessed through cell counting kit-8 (CCK-8) and terminal deoxynucleotidyl transferase dUTP nick end labeling assays, respectively, to determine the injury to the HUVECs. The viability loss in the H2O2-induced HUVECs was markedly restored in a concentration-dependent manner by pretreatment with quercetin or taraxasterol. This effect was accompanied by significantly decreased expression of vascular cell adhesion molecule 1 (VCAM-1) and cluster of differentiation (CD)80 for taraxasterol and that of CD80 for quercetin. In conclusion, the present study showed the protective effects of quercetin and taraxasterol against cell injury and inflammation in HUVECs and indicated that the effects were mediated via the downregulation of VCAM-1 and CD80 expression. This study has therefore served as a preliminary investigation on the anti-atherosclerotic and cardiovascular protective effects of quercetin and taraxasterol as dietary supplements. PMID:26622474

  17. Selection of filamentous fungi of the Beauveria genus able to metabolize quercetin like mammalian cells

    PubMed Central

    de M. B. Costa, Eula Maria; Pimenta, Fabiana Cristina; Luz, Wolf Christian; de Oliveira, Valéria

    2008-01-01

    Microbial biotransformations constitute an important alternative as models for drug metabolism study in mammalians and have been used for the industrial synthesis of chemicals with pharmaceutical purposes. Several microorganisms with unique biotransformation ability have been found by intensive screening and put in commercial applications. Ten isolates of Beauveria sp genus filamentous fungi, isolated from soil in the central Brazil, and Beauveria bassiana ATCC 7159 were evaluated for their capability of quercetin biotransformation. Biotransformation processes were carried out for 24 up to 96 hours and monitored by mass spectrometry analyses of the culture broth. All strains were able to metabolize quercetin, forming mammalian metabolites. The results were different from those presented by other microorganisms previously utilized, attrackting attention because of the great diversity of reactions. Methylated, sulphated, monoglucuronidated, and glucuronidated conjugated metabolites were simultaneously detected. PMID:24031237

  18. Supraphysiological Levels of Quercetin Glycosides are Required to Alter Mineralization in Saos2 Cells

    PubMed Central

    Nash, Leslie A.; Peters, Sandra J.; Sullivan, Philip J.; Ward, Wendy E.

    2016-01-01

    Flavonoid intake is positively correlated to bone mineral density (BMD) in women. Flavonoids such as quercetin exhibit strong anti-oxidant and anti-inflammatory activity that may be beneficial for bone health. Quercetin, previously shown to positively influence osteoblasts, is metabolized into glycosides including rutin and hyperoside. We compared the effects of these glycosides on mineralization in human osteoblast (Saos2) cells. Administration of rutin (≥25 µM) and hyperoside (≥5 µM) resulted in higher mineral content, determined using the alizarin red assay. This was accompanied by higher alkaline phosphatase activity with no cell toxicity. The expression of osteopontin, sclerostin, TNFα and IL6, known stimuli for decreasing osteoblast activity, were reduced with the addition of rutin or hyperoside. In summary, rutin and hyperoside require supraphysiological levels, when administered individually, to positively influence osteoblast activity. This information may be useful in developing nutraceuticals to support bone health. PMID:27136576

  19. Data for induction of cytotoxic response by natural and novel quercetin glycosides.

    PubMed

    Haskins, Alexis H; Su, Cathy; Engen, Anya; Salinas, Victoria A; Maeda, Junko; Uesaka, Mitsuru; Aizawa, Yasushi; Kato, Takamitsu A

    2016-03-01

    The flavonoids quercetin, and its natural glycosides isoquercetin and rutin, are phytochemicals commonly consumed in plant-derived foods and used as a food beverage additive. Semi-synthetic maltooligosyl isoquercetin, monoglucosyl rutin and maltooligosyl rutin were developed by synthetic glycosylation to improve their water solubility for food and other applications. Using a system of Chinese hamster ovary (CHO) cells, this study examined the differences in cytotoxic responses induced by short and continuous exposure of natural and synthetic flavonoids. By assessing cell viability after short term exposure and clonogenicity with continuous exposure under various flavonoids, quercetin aglycone is confirmed to be the most cytotoxic flavonoids, and heavily glucosylated maltooligosyl rutin was the least cytotoxic. The other heavily glucosylated maltooligosyl isoquercetin showed intermediate cytotoxicity and similar toxicity as isoquercetin. PMID:26862569

  20. Supraphysiological Levels of Quercetin Glycosides are Required to Alter Mineralization in Saos2 Cells.

    PubMed

    Nash, Leslie A; Peters, Sandra J; Sullivan, Philip J; Ward, Wendy E

    2016-01-01

    Flavonoid intake is positively correlated to bone mineral density (BMD) in women. Flavonoids such as quercetin exhibit strong anti-oxidant and anti-inflammatory activity that may be beneficial for bone health. Quercetin, previously shown to positively influence osteoblasts, is metabolized into glycosides including rutin and hyperoside. We compared the effects of these glycosides on mineralization in human osteoblast (Saos2) cells. Administration of rutin (≥25 µM) and hyperoside (≥5 µM) resulted in higher mineral content, determined using the alizarin red assay. This was accompanied by higher alkaline phosphatase activity with no cell toxicity. The expression of osteopontin, sclerostin, TNFα and IL6, known stimuli for decreasing osteoblast activity, were reduced with the addition of rutin or hyperoside. In summary, rutin and hyperoside require supraphysiological levels, when administered individually, to positively influence osteoblast activity. This information may be useful in developing nutraceuticals to support bone health. PMID:27136576

  1. Nitrosyl hydride (HNO) replaces dioxygen in nitroxygenase activity of manganese quercetin dioxygenase

    PubMed Central

    Kumar, Murugaeson R.; Zapata, Adrian; Ramirez, Alejandro J.; Bowen, Sara K.; Francisco, Wilson A.; Farmer, Patrick J.

    2011-01-01

    Quercetin dioxygenase (QDO) catalyzes the oxidation of the flavonol quercetin with dioxygen, cleaving the central heterocyclic ring and releasing CO. The QDO from Bacillus subtilis is unusual in that it has been shown to be active with several divalent metal cofactors such as Fe, Mn, and Co. Previous comparison of the catalytic activities suggest that Mn(II) is the preferred cofactor for this enzyme. We herein report the unprecedented substitution of nitrosyl hydride (HNO) for dioxygen in the activity of Mn-QDO, resulting in the incorporation of both N and O atoms into the product. Turnover is demonstrated by consumption of quercetin and other related substrates under anaerobic conditions in the presence of HNO-releasing compounds and the enzyme. As with dioxygenase activity, a nonenzymatic base-catalyzed reaction of quercetin with HNO is observed above pH 7, but no enhancement of this basal reactivity is found upon addition of divalent metal salts. Unique and regioselective N-containing products (14N/15N) have been characterized by MS analysis for both the enzymatic and nonenzymatic reactions. Of the several metallo-QDO enzymes examined for nitroxygenase activity under anaerobic condition, only the Mn(II) is active; the Fe(II) and Co(II) substituted enzymes show little or no activity. This result represents an enzymatic catalysis which we denote nitroxygenase activity; the unique reactivity of the Mn-QDO suggests a metal-mediated electron transfer mechanism rather than metal activation of the substrate’s inherent base-catalyzed reactivity. PMID:22084064

  2. 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

  3. A dietary pattern rich in lignans, quercetin and resveratrol decreases the risk of oesophageal cancer.

    PubMed

    Lin, Yulan; Yngve, Agneta; Lagergren, Jesper; Lu, Yunxia

    2014-12-28

    Dietary lignans, quercetin and resveratrol have oestrogenic properties, and animal studies suggest that they synergistically decrease cancer risk. A protective effect of lignans on the development of oesophageal cancer in humans has recently been demonstrated, and the present study aimed to test whether these three phytochemicals synergistically decrease the risk of oesophageal cancer. Data from a Swedish nationwide population-based case-control study that recruited 181 cases of oesophageal adenocarcinoma (OAC), 158 cases of oesophageal squamous-cell carcinoma (OSCC), 255 cases of gastro-oesophageal junctional adenocarcinoma (JAC) and 806 controls were analysed. Exposure data were collected through face-to-face interviews and questionnaires. The intake of lignans, quercetin and resveratrol was assessed using a sixty-three-item FFQ. Reduced-rank regression was used to assess a dietary pattern, and a simplified dietary pattern score was categorised into quintiles on the basis of the distribution among the control subjects. Unconditional multivariable logistic regression provided OR with 95% CI, adjusted for all the potential risk factors. A dietary pattern rich in lignans, quercetin and resveratrol was mainly characterised by a high intake of tea, wine, lettuce, mixed vegetables, tomatoes, and whole-grain bread and a low intake of milk. There were dose-dependent associations between simplified dietary pattern scores and all types of oesophageal cancer (all P for trend < 0.05). On comparing the highest quintiles with the lowest, the adjusted OR were found to be 0.24 (95% CI 0.12, 0.49) for OAC, 0.31 (95% CI 0.15, 0.65) for OSCC, and 0.49 (95% CI 0.28, 0.84) for JAC. The results of the present study indicate that a dietary pattern characterised by the intake of lignans, quercetin and resveratrol may play a protective role in the development of oesophageal cancer in the Swedish population. PMID:25345471

  4. Exploring the antioxidant property of bioflavonoid quercetin in preventing DNA glycation: A calorimetric and spectroscopic study

    SciTech Connect

    Sengupta, Bidisa . E-mail: bidisa@fy.chalmers.se; Uematsu, Takashi; Jacobsson, Per; Swenson, Jan

    2006-01-06

    Reducing sugars for example glucose, fructose, etc., and their phosphate derivatives non-enzymatically glycate biological macromolecules (e.g., proteins, DNA and lipids) and is related to the production of free radicals. Here we present a novel study, using differential scanning calorimetry (DSC) along with UV/Vis absorption and photon correlation spectroscopy (PCS), on normal and glycated human placenta DNA and have explored the antioxidant property of the naturally occurring polyhydroxy flavone quercetin (3,3',4',5,7-pentahydroxyflavone) in preventing the glycation. The decrease in the absorption intensity of DNA in presence of sugars clearly indicates the existence of sugar molecules between the two bases of a base pair in the duplex DNA molecule. Variations were perceptible in the PCS relaxation profiles of normal and glycated DNA. The melting temperature of placenta DNA was decreased when glycated suggesting a decrease in the structural stability of the double-stranded glycated DNA. Our DSC and PCS data showed, for the first time, that the dramatic changes in the structural properties of glycated DNA can be prevented to a significant extent by adding quercetin. This study provides valuable insights regarding the structure, function, and dynamics of normal and glycated DNA molecules, underlying the manifestation of free radical mediated diseases, and their prevention using therapeutically active naturally occurring flavonoid quercetin.

  5. Complexation of quercetin with three kinds of cyclodextrins: An antioxidant study

    NASA Astrophysics Data System (ADS)

    Jullian, Carolina; Moyano, Lorena; Yañez, Claudia; Olea-Azar, Claudio

    2007-05-01

    The slightly water-soluble flavonoid quercetin (QUE) and its inclusion with either β-cyclodextrin (βCD), hydroxypropyl-β-cyclodextrin (HP-βCD) or sulfobutyl ether-β-cyclodextrin (SBE-βCD) were investigated. The stoichiometric ratios and stability constants describing the extent of formation of the complexes have been determined by phase-solubility measurements; in all cases type-A L diagrams have been obtained (soluble 1:1 complexes). The results showed that the inclusion ability of βCD and its derivatives was the order: SBE-βCD > HP-βCD > βCD. Kinetic studies of DPPH rad with QUE and CDs complexes were done. The results obtained indicated that the QUE-SBE-βCD complex was the most reactive form. The scavenging capability of QUE and CDs complexes with DPPH rad and galvinoxyl was studied using ESR spectroscopy. All complexes showed a higher scavenging capability with both radicals, compare quercetin in water. Beside, these results indicated that the complexes formed maintained the quercetin antioxidant activity.

  6. 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

  7. Camelina sativa defatted seed meal contains both alkyl sulfinyl glucosinolates and quercetin that synergize bioactivity.

    PubMed

    Das, Nilanjan; Berhow, Mark A; Angelino, Donato; Jeffery, Elizabeth H

    2014-08-20

    Camelina sativa L. Crantz is under development as a novel oilseed crop, yet bioefficacy of camelina phytochemicals is unknown. Defatted camelina seed meal contains two major aliphatic glucosinolates (GSLs), glucoarabin (9-(methylsulfinyl)nonylglucosinolate; GSL 9) and glucocamelinin (10-(methylsulfinyl)decylglucosinolate; GSL 10), with traces of a third, 11(methylsulfinyl)undecylglucosinolate and several flavonoids, mostly quercetin glycosides. In Hepa1c1c7 cells, hydrolyzed GSLs (hGSLs) 9 and 10 upregulated the phase II detoxification enzyme quinone reductase (NQO1), with no effect on cytochrome P450 (CYP) 1A1 activity. Isobologram graphs revealed synergy of NQO1 induction for a combination of hGSL 9 and quercetin. These findings suggest that defatted camelina seed meal should be evaluated for anticancer activity, similar to broccoli and other Brassicaceae family members. Interestingly, synergy of NQO1 induction was also seen for physiologically relevant doses of sulforaphane (SF) and quercetin, two key bioactives present in broccoli. This suggests that SF within broccoli may be more potent than purified SF. PMID:25050614

  8. Human exposure modelling of quercetin in onions (Allium cepa L.) following thermal processing.

    PubMed

    Harris, S; Brunton, N; Tiwari, U; Cummins, E

    2015-11-15

    Post-harvest treatment can influence levels of secondary metabolites in fruits and vegetables. Onions contain high levels of quercetin but are commonly heat-treated before consumption. Hence, the objective of this study was to examine the effect of cooking treatments on the flavonoid (3,4'-Qdg and 4'-Qmg) concentrations in onion and to determine, by simulation modelling, probable human exposure. Onion samples (n=3) were cooked using three processes (fry, bake and steam) for three time intervals (5, 10 and 15 min). Frying (<10 min) was the ideal cooking method which retained concentrations of 3,4'-Qdg and 4'-Qmg at >50%. Thermal processing (>10 min) was shown to decrease quercetin content in all samples. The simulation model predicted human absorption and exposure. Steaming (15 min) resulted in the lowest quercetin exposure, with mean values of 4000 and 400 μg/day for 3,4'-Qdg and 4'-Qmg, respectively. Untreated onions had mean exposures of 14,000 and 3000 μg/day for 3,4'-Qdg and 4'-Qmg, respectively. PMID:25977008

  9. Apigenin and quercetin promote. Delta. pH-dependent accumulation of IAA in membrane vesicles

    SciTech Connect

    Woolard, D.D.; Clark, K.A. )

    1990-05-01

    Flavonoids may act as regulators of polar auxin transport. In the presence of a pH gradient (pH 8{sub in}/6{sub out}) the flavonoids quercetin and apigenin, as well as the synthetic herbicide napthylphthalamic acid (NPA), promote the accumulation of IAA in membrane vesicles from dark-grown zucchini hypocotyls. Simultaneous accumulation of {sup 3}H-IAA (10 nM) and {sup 14}C-butyric acid (5 {mu}M; included as a pH probe) was determined by a filtration assay after incubating the vesicles with 3 nM to 100 {mu}M quercetin, apigenin, NPA or unlabeled IAA. Maximal stimulation (% of Control) was observed with 3 {mu}M NPA (130%), 1 {mu}M quercetin (120%), or 3 {mu}M apigenin (115%); {Delta}pH was not affected by these concentrations. As reported by others, IAA uptake was saturable: 1 {mu}M unlabeled IAA eliminated {Delta}pH-dependent uptake of {sup 3}H-IAA without altering {Delta}pH. However, at 30 to 100 {mu}M, every compound tested collapsed the imposed pH gradient and therefore abolished specific {sup 3}H-IAA uptake.

  10. Characterization of putative receptors specific for quercetin on bovine aortic smooth-muscle cells

    SciTech Connect

    Yu, S.C.; Becker, C.G.

    1986-03-01

    The authors have reported that tobacco glycoprotein (TGP), rutin-bovine serum albumin conjugates (R-BSA), quercetin, and chlorogenic acid are mitogenic for bovine aortic smooth-muscle cells (SMC). To investigate whether there are binding sites or receptors for these polyphenol-containing molecules on SMC, the authors have synthesized /sup 125/I-labeled rutin-bovine serum albumin ((/sup 125/I)R-BSA) of high specific activity (20 Ci/mmol). SMC were isolated from a bovine thoracic aorta and maintained in Eagle's minimum essential medium with 10% calf serum in culture. These SMC at early subpassages were suspended (3-5 x 10/sup 7/ cells/ml) in phosphate-buffered saline and incubated with (/sup 125/I)R-BSA (10 pmol) in the presence or absence of 200-fold unlabeled R-BSA, TGP, BSA, rutin, quercetin or related polyphenols, and catecholamines. Binding of (/sup 125/I)R-BSA to SMC was found to be reproducible and the radioligand was displaced by R-BSA, and also by TGP, rutin, quercetin, and chlorogenic acid, but not by BSA, ellagic acid, naringin, hesperetin, dopamine, epinephrine, or isoproterenol. The binding was saturable, reversible, and pH-dependent. These results demonstrate the presence of specific binding sites for quercetinon arterial SMC.

  11. Inclusion complexes of quercetin with three β-cyclodextrins derivatives at physiological pH: Spectroscopic study and antioxidant activity

    NASA Astrophysics Data System (ADS)

    Liu, Min; Dong, Lina; Chen, Aiju; Zheng, Yan; Sun, Dezhi; Wang, Xu; Wang, Bingquan

    2013-11-01

    Properties of the inclusion complexes of quercetin (QUE) with sulfobutyl ether-β-cyclodextrin (SBE-β-CD), hydroxypropyl-β-cyclodextrin (HP-β-CD), and methylated-β-cyclodextrin (M-β-CD) in tris-HCl buffer solutions of pH 7.40 were investigated. The stoichiometry and thermodynamic parameters for the complexation process (stability constants K, Gibbs free energy change ΔG, enthalpy change ΔH and entropy change ΔS) were determined using phase-solubility and fluorescence spectra analysis. The thermodynamic studies indicated that the inclusion reactions between QUE and the three β-CDs are enthalpy-driven processes. Proton nuclear magnetic resonance spectroscopy indicated that B-ring, C-ring, and part of A-ring of QUE interact with the cavity of β-CDs. The antioxidant activity of QUE and its inclusion complexes were determined by the scavenging of stable radical DPPH*. The results showed that the complexed QUE/CDs were more effective than free QUE, with the QUE/SBE-β-CD complex as the best form.

  12. Multifaceted preventive effects of single agent quercetin on a human prostate adenocarcinoma cell line (PC-3): implications for nutritional transcriptomics and multi-target therapy.

    PubMed

    Noori-Daloii, Mohammad R; Momeny, Majid; Yousefi, Mehdi; Shirazi, Forough Golsaz; Yaseri, Mehdi; Motamed, Nasrin; Kazemialiakbar, Nazanin; Hashemi, Saeed

    2011-12-01

    The aim of the present study is to evaluate the effects of quercetin, a dietary flavonoid, on human prostate adenocarcinoma PC-3 cells. Lactate dehydrogenase (LDH) release, microculture tetrazolium test (MTT assay) and real-time PCR array were employed to evaluate the effects of quercetin on cell cytotoxicity, cell proliferation and expression of various genes in PC-3 cell line. Quercetin inhibited cell proliferation and modulated the expression of genes involved in DNA repair, matrix degradation and tumor invasion, angiogenesis, apoptosis, cell cycle, metabolism and glycolysis. No cytotoxicity of quercetin on PC-3 cells was observed. Taken together, as shown by the issues of the current study, the manifold inhibitory effects of quercetin on PC-3 cells may introduce quercetin as an efficacious anticancer agent in order to be used in the future nutritional transcriptomic investigations and multi-target therapy to overcome the therapeutic impediments against prostate cancer. PMID:20596804

  13. 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

  14. Flavonoid (myricetin, quercetin, kaempferol, luteolin, and apigenin) content of edible tropical plants.

    PubMed

    Miean, K H; Mohamed, S

    2001-06-01

    Studies were conducted on the flavonoids (myricetin, quercetin, kaempferol, luteolin, and apigenin) contents of 62 edible tropical plants. The highest total flavonoids content was in onion leaves (1497.5 mg/kg quercetin, 391.0 mg/kg luteolin, and 832.0 mg/kg kaempferol), followed by Semambu leaves (2041.0 mg/kg), bird chili (1663.0 mg/kg), black tea (1491.0 mg/kg), papaya shoots (1264.0 mg/kg), and guava (1128.5 mg/kg). The major flavonoid in these plant extracts is quercetin, followed by myricetin and kaempferol. Luteolin could be detected only in broccoli (74.5 mg/kg dry weight), green chili (33.0 mg/kg), bird chili (1035.0 mg/kg), onion leaves (391.0 mg/kg), belimbi fruit (202.0 mg/kg), belimbi leaves (464.5 mg/kg), French bean (11.0 mg/kg), carrot (37.5 mg/kg), white radish (9.0 mg/kg), local celery (80.5 mg/kg), limau purut leaves (30.5 mg/kg), and dried asam gelugur (107.5 mg/kg). Apigenin was found only in Chinese cabbage (187.0 mg/kg), bell pepper (272.0 mg/kg), garlic (217.0 mg/kg), belimbi fruit (458.0 mg/kg), French peas (176.0 mg/kg), snake gourd (42.4 mg/kg), guava (579.0 mg/kg), wolfberry leaves (547.0 mg/kg), local celery (338.5 mg/kg), daun turi (39.5 mg/kg), and kadok (34.5 mg/kg). In vegetables, quercetin glycosides predominate, but glycosides of kaempferol, luteolin, and apigenin are also present. Fruits contain almost exclusively quercetin glycosides, whereas kaempferol and myricetin glycosides are found only in trace quantities. PMID:11410016

  15. Quercetin reversed lipopolysaccharide-induced inhibition of osteoblast differentiation through the mitogen‑activated protein kinase pathway in MC3T3-E1 cells.

    PubMed

    Wang, Xin-Chun; Zhao, Nzhi-Jun; Guo, Chun; Chen, Jing-Tao; Song, Jin-Ling; Gao, Li

    2014-12-01

    Quercetin, a flavonoid found in onions and other vegetables, has potential inhibitory effects on bone resorption in vivo and in vitro. In our previous study it was identified that quercetin triggered the apoptosis of lipopolysaccharide (LPS)‑induced osteoclasts and inhibited bone resorption. Currently, little information is available detailing the effect of quercetin on osteoblast differentiation and bone formation in bacteria‑induced inflammatory diseases. The present study aimed to investigate the effect of quercetin on osteoblast differentiation in MC3T3‑E1 osteoblasts stimulated with LPS. LPS significantly downregulated the mRNA expression of osteoblast‑related genes in the MC3T3‑E1 cells. By contrast, quercetin significantly restored the LPS‑suppressed mRNA expression of osteoblast‑related genes in a dose‑dependent manner. Quercetin also restored the protein expression of Osterix in MC3T3‑E1 cells suppressed by LPS. Furthermore, quercetin selectively triggered the activation of the mitogen‑activated protein kinase (MAPK) pathway by enhancing the expression of extracellular signal-regulated kinase and reducing the expression of c‑Jun N‑terminal kinase. These data suggest that quercetin reversed the inhibition of osteoblast differentiation induced by LPS through MAPK signaling. These findings suggest that quercetin may be of potential use as a therapeutic agent to restore osteoblast function in bacteria‑induced bone diseases. PMID:25323558

  16. Quercetin Feeding in Newborn Dairy Calves Cannot Compensate Colostrum Deprivation: Study on Metabolic, Antioxidative and Inflammatory Traits.

    PubMed

    Gruse, Jeannine; Kanitz, Ellen; Weitzel, Joachim M; Tuchscherer, Armin; Stefaniak, Tadeusz; Jawor, Paulina; Wolffram, Siegfried; Hammon, Harald M

    2016-01-01

    Immaturity of the neonatal immune system is causative for high morbidity in calves and colostrum intake is crucial for acquiring passive immunity. Pathogenesis is promoted by reactive oxygen species accumulating at birth if counter-regulation is inadequate. The flavonol quercetin exerts antioxidative and anti-inflammatory effects that may enhance neonatal health. The aim of this work was to study effects of quercetin feeding on metabolic, antioxidative and inflammatory parameters in neonatal calves to investigate whether quercetin could compensate for insufficient colostrum supply. Twenty-eight newborn calves were assigned to two dietary groups fed colostrum or milk-based formula on day 1 and 2 and milk replacer thereafter. From day 2 onwards, 7 calves per diet group were additionally fed quercetin aglycone (50 mg/(kg body weight × day)). Blood samples were taken repeatedly to measure plasma concentrations of flavonols, glucose, lactate, total protein, albumin, urea, non-esterified fatty acids, triglycerides, cholesterol, insulin, glucagon, cortisol, immunoglobulins, fibrinogen, haptoglobin and serum amyloid A. Trolox equivalent antioxidative capacity, ferric reducing ability of plasma, thiobarbituric acid reactive species and F2-isoprostanes were analyzed to evaluate plasma antioxidative status. Expression of tumor necrosis factor, interleukin-1α, interleukin-1β, serum amyloid A, haptoglobin, fibrinogen, C-reactive protein, catalase, glutathione peroxidase and superoxide dismutase mRNA were measured in liver tissue on day 8. Plasma flavonol concentrations were detectable only after quercetin-feeding without differences between colostrum and formula feeding. Plasma glucose, lactate, total protein, immunoglobulins, triglycerides, cholesterol, trolox equivalent antioxidative capacity and thiobarbituric acid reactive species were higher after colostrum feeding. Body temperature, fecal fluidity and plasma concentrations of cortisol and haptoglobin were higher in

  17. Quercetin reduces cyclin D1 activity and induces G1 phase arrest in HepG2 cells

    PubMed Central

    ZHOU, JIN; LI, LU; FANG, LI; XIE, HUA; YAO, WENXIU; ZHOU, XIANG; XIONG, ZHUJUAN; WANG, LI; LI, ZHIXI; LUO, FENG

    2016-01-01

    Quercetin is able to inhibit proliferation of malignant tumor cells; however, the exact mechanism involved in this biological process remains unclear. The current study utilized a quantitative proteomic analysis to explore the antitumor mechanisms of quercetin. The leucine of HepG2 cells treated with quercetin was labeled as d3 by stable isotope labeling by amino acids in cell culture (SILAC). The isotope peaks of control HepG2 cells were compared with the d3-labeled HepG2 cells by mass spectrometry (MS) to identify significantly altered proteins. Reverse transcription-polymerase chain reaction (RT-PCR) and western blot analyses were subsequently employed to verify the results of the MS analysis. A flow cytometry assay was designed to observe the influence of various quercetin treatment concentrations on the cell cycle distribution of HepG2 cells. The results indicated that quercetin is able to substantially inhibit proliferation of HepG2 cells and induce an obvious morphological alteration of cells. According to the MS results, the 70 credibly-changed proteins that were identified may play important roles in multiple cellular processes, including protein synthesis, signaling, cytoskeletal processes and metabolism. Among these functional proteins, the expression of cyclin D1 (CCND1) was found to be significantly decreased. RT-PCR and western blot analyses verified the SILAC-MS results of decreased CCND1 expression. In summary, flow cytometry revealed that quercetin is able to induce G1 phase arrest in HepG2 cells. Based on the aforementioned observations, it is suggested that quercetin exerts antitumor activity in HepG2 cells through multiple pathways, including interfering with CCND1 gene expression to disrupt the cell cycle and proliferation of HepG2 cells. In the future, we aim to explore this effect in vivo. PMID:27347174

  18. Single-dose oral quercetin improves redox status but does not affect heat shock response in mice.

    PubMed

    Chen, Yifan; Islam, Aminul; Abraham, Preetha; Deuster, Patricia

    2014-07-01

    Inflammation and oxidative stress are considered as likely contributors to heat injury. However, their roles in regulating the heat shock response in vivo remain unclear. We tested the hypothesis that acute quercetin treatment would improve redox status and reduce heat shock responses in mice. Mice underwent two heat tests before and after single oral administration of either quercetin (15 mg/kg) or vehicle. We measured physiologic and biochemical responses in mice during and 18 to 22 hours after heat tests, respectively. There were no significant differences in core temperature, heart rate, or blood pressure between quercetin and vehicle groups during heat exposure. Mice with relatively severe hyperthermia during the pretreatment heat test showed a significant trend toward a lower peak core temperature during the heat test after quercetin treatment. Compared with mice not exposed to heat, quercetin-treated mice had significantly lower interleukin 6 (P < .01) and higher superoxide dismutase levels (P < .01), whereas vehicle-treated mice had significantly lower total glutathione and higher 8-isoprostane levels in the circulation after heat exposure. Heat exposure significantly elevated heat shock proteins (HSPs) 72 and 90 and heat shock factor 1 levels in mouse liver, heart, and skeletal muscles, but no significant differences in tissue HSPs and heat shock factor 1 were found between quercetin- and vehicle-treated mice. These results suggest that a single moderate dose of quercetin is sufficient to alter redox status but not heat stress response in mice. Acute adaptations of peripheral tissues to heat stress may not be mediated by systemic inflammatory and redox state in vivo. PMID:25150121

  19. Quercetin Feeding in Newborn Dairy Calves Cannot Compensate Colostrum Deprivation: Study on Metabolic, Antioxidative and Inflammatory Traits

    PubMed Central

    Gruse, Jeannine; Kanitz, Ellen; Weitzel, Joachim M.; Tuchscherer, Armin; Stefaniak, Tadeusz; Jawor, Paulina; Wolffram, Siegfried; Hammon, Harald M.

    2016-01-01

    Immaturity of the neonatal immune system is causative for high morbidity in calves and colostrum intake is crucial for acquiring passive immunity. Pathogenesis is promoted by reactive oxygen species accumulating at birth if counter-regulation is inadequate. The flavonol quercetin exerts antioxidative and anti-inflammatory effects that may enhance neonatal health. The aim of this work was to study effects of quercetin feeding on metabolic, antioxidative and inflammatory parameters in neonatal calves to investigate whether quercetin could compensate for insufficient colostrum supply. Twenty-eight newborn calves were assigned to two dietary groups fed colostrum or milk-based formula on day 1 and 2 and milk replacer thereafter. From day 2 onwards, 7 calves per diet group were additionally fed quercetin aglycone (50 mg/(kg body weight × day)). Blood samples were taken repeatedly to measure plasma concentrations of flavonols, glucose, lactate, total protein, albumin, urea, non-esterified fatty acids, triglycerides, cholesterol, insulin, glucagon, cortisol, immunoglobulins, fibrinogen, haptoglobin and serum amyloid A. Trolox equivalent antioxidative capacity, ferric reducing ability of plasma, thiobarbituric acid reactive species and F2-isoprostanes were analyzed to evaluate plasma antioxidative status. Expression of tumor necrosis factor, interleukin-1α, interleukin-1β, serum amyloid A, haptoglobin, fibrinogen, C-reactive protein, catalase, glutathione peroxidase and superoxide dismutase mRNA were measured in liver tissue on day 8. Plasma flavonol concentrations were detectable only after quercetin-feeding without differences between colostrum and formula feeding. Plasma glucose, lactate, total protein, immunoglobulins, triglycerides, cholesterol, trolox equivalent antioxidative capacity and thiobarbituric acid reactive species were higher after colostrum feeding. Body temperature, fecal fluidity and plasma concentrations of cortisol and haptoglobin were higher in

  20. Quercetin prevents ethanol-induced iron overload by regulating hepcidin through the BMP6/SMAD4 signaling pathway.

    PubMed

    Tang, Yuhan; Li, Yanyan; Yu, Haiyan; Gao, Chao; Liu, Liang; Chen, Shaodan; Xing, Mingyou; Liu, Liegang; Yao, Ping

    2014-06-01

    Emerging evidence has demonstrated that chronic ethanol exposure induces iron overload, enhancing ethanol-mediated liver damage. The purpose of this study was to explore the effects of the naturally occurring compound quercetin on ethanol-induced iron overload and liver damage, focusing on the signaling pathway of the iron regulatory hormone hepcidin. Adult male C57BL/6J mice were pair-fed with isocaloric-Lieber De Carli diets containing ethanol (accounting for 30% of total calories) and/or carbonyl iron (0.2%) and treated with quecertin (100 mg/kg body weight) for 15 weeks. Mouse primary hepatocytes were incubated with ethanol (100 mM) and quercetin (100 μM) for 24 h. Mice exposed to either ethanol or iron presented significant fatty infiltration and iron deposition in the liver; these symptoms were exacerbated in mice cotreated with ethanol and iron. Quercetin attenuated the abnormity induced by ethanol and/or iron. Ethanol suppressed BMP6 and intranuclear SMAD4 as well as decreased hepcidin expression. These effects were partially alleviated by quercetin supplementation in mice and hepatocytes. Importantly, ethanol caused suppression of SMAD4 binding to the HAMP promoter and of hepcidin messenger RNA expression. These effects were exacerbated by anti-BMP6 antibody and partially alleviated by quercetin or human recombinant BMP6 in cultured hepatocytes. In contrast, co-treatment with iron and ethanol, especially exposure of iron alone, activated BMP6/SMAD4 pathway and up-regulated hepcidin expression, which was also normalized by quercetin in vivo. Quercetin prevented ethanol-induced hepatic iron overload different from what carbonyl iron diet elicited in the mechanism, by regulating hepcidin expression via the BMP6/SMAD4 signaling pathway. PMID:24746831

  1. 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

  2. Improved stability and skin permeability of sodium hyaluronate-chitosan multilayered liposomes by Layer-by-Layer electrostatic deposition for quercetin delivery.

    PubMed

    Jeon, Soha; Yoo, Cha Young; Park, Soo Nam

    2015-05-01

    Layer-by-Layer (LbL) technology, based on the electrostatic interaction of polyelectrolytes, is used to improve the stability of drug delivery systems. In the present study, we developed multilayered liposomes with up to 10 alternating layers based on LbL deposition of hyaluronate-chitosan for transdermal delivery. Dihexadecyl phosphate was used to provide liposomes with a negative charge; the liposomes were subsequently coated with cationic chitosan (CH) followed by anionic sodium hyaluronate (HA). The resulting particles had a cumulative size of 528.28±29.22nm and an alternative change in zeta potential. Differential scanning calorimetry (DSC) and transmission electron microscopy (TEM) revealed that the multilayered liposomes formed a spherical polyelectrolyte complex (PEC) after deposition. Observations in size distribution after 1 week found that the particles coated with even layers of polyelectrolytes, hyaluronate and chitosan (HA-CH), were more stable than the odd layers. Membrane stability in the presence of the surfactant Triton X-100 increased with an increase in bilayers as compared to uncoated liposomes. An increase in the number of bilayers deposited on the liposomal surface resulted in a sustained release of quercetin, with release kinetics that fit the Korsmeyer-Peppas model. In an in vitro skin permeation study, negatively charged (HA-CH)-L and positively charged CH-L were observed to have similar skin permeability, which were superior to uncoated liposomes. These results indicate that multilayered liposomes properly coated with polyelectrolytes of HA and CH by electrostatic interaction improve stability and can also function as potential drug delivery system for the transdermal delivery of the hydrophobic antioxidant quercetin. PMID:25819360

  3. The Effect of Quercetin on the Osteogenesic Differentiation and Angiogenic Factor Expression of Bone Marrow-Derived Mesenchymal Stem Cells

    PubMed Central

    Zhou, Yuning; Wu, Yuqiong; Jiang, Xinquan; Zhang, Xiuli; Xia, Lunguo; Lin, Kaili; Xu, Yuanjin

    2015-01-01

    Bone marrow-derived mesenchymal stem cells (BMSCs) are widely used in regenerative medicine in light of their ability to differentiate along the chondrogenic and osteogenic lineages. As a type of traditional Chinese medicine, quercetin has been preliminarily reported to promote osteogenic differentiation in osteoblasts. In the present study, the effects of quercetin on the proliferation, viability, cellular morphology, osteogenic differentiation and angiogenic factor secretion of rat BMSCs (rBMSCs) were examined by MTT assay, fluorescence activated cell sorter (FACS) analysis, real-time quantitative PCR (RT-PCR) analysis, alkaline phosphatase (ALP) activity and calcium deposition assays, and Enzyme-linked immunosorbent assay (ELISA). Moreover, whether mitogen-activated protein kinase (MAPK) signaling pathways were involved in these processes was also explored. The results showed that quercetin significantly enhanced the cell proliferation, osteogenic differentiation and angiogenic factor secretion of rBMSCs in a dose-dependent manner, with a concentration of 2 μM achieving the greatest stimulatory effect. Moreover, the activation of the extracellular signal-regulated protein kinases (ERK) and p38 pathways was observed in quercetin-treated rBMSCs. Furthermore, these induction effects could be repressed by either the ERK inhibitor PD98059 or the p38 inhibitor SB202190, respectively. These data indicated that quercetin could promote the proliferation, osteogenic differentiation and angiogenic factor secretion of rBMSCs in vitro, partially through the ERK and p38 signaling pathways. PMID:26053266

  4. 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

  5. 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

  6. The Effect of Quercetin on the Osteogenesic Differentiation and Angiogenic Factor Expression of Bone Marrow-Derived Mesenchymal Stem Cells.

    PubMed

    Zhou, Yuning; Wu, Yuqiong; Jiang, Xinquan; Zhang, Xiuli; Xia, Lunguo; Lin, Kaili; Xu, Yuanjin

    2015-01-01

    Bone marrow-derived mesenchymal stem cells (BMSCs) are widely used in regenerative medicine in light of their ability to differentiate along the chondrogenic and osteogenic lineages. As a type of traditional Chinese medicine, quercetin has been preliminarily reported to promote osteogenic differentiation in osteoblasts. In the present study, the effects of quercetin on the proliferation, viability, cellular morphology, osteogenic differentiation and angiogenic factor secretion of rat BMSCs (rBMSCs) were examined by MTT assay, fluorescence activated cell sorter (FACS) analysis, real-time quantitative PCR (RT-PCR) analysis, alkaline phosphatase (ALP) activity and calcium deposition assays, and Enzyme-linked immunosorbent assay (ELISA). Moreover, whether mitogen-activated protein kinase (MAPK) signaling pathways were involved in these processes was also explored. The results showed that quercetin significantly enhanced the cell proliferation, osteogenic differentiation and angiogenic factor secretion of rBMSCs in a dose-dependent manner, with a concentration of 2 μM achieving the greatest stimulatory effect. Moreover, the activation of the extracellular signal-regulated protein kinases (ERK) and p38 pathways was observed in quercetin-treated rBMSCs. Furthermore, these induction effects could be repressed by either the ERK inhibitor PD98059 or the p38 inhibitor SB202190, respectively. These data indicated that quercetin could promote the proliferation, osteogenic differentiation and angiogenic factor secretion of rBMSCs in vitro, partially through the ERK and p38 signaling pathways. PMID:26053266

  7. Effects of quercetin on predator stress-related hematological and behavioral alterations in pregnant rats and their offspring.

    PubMed

    Toumi, Mohamed L; Merzoug, Sameha; Tahraoui, Abdelkrim

    2016-06-01

    This study aims at investigating the effect of a psychogenic stress during gestation on the behaviour and haematological indices in dams as well as on the neonatal haematological status and periadolescent behaviour in their offspring. Moreover, the ability of quercetin, a natural flavonoid, to prevent the stress-induced changes was estimated. Pregnant Wistar rats were pretreated with quercetin before the exposure to a predator stress on gestational day 19. Post-stress maternal anxiety-like behaviour was assessed with a concomitant haematological analysis. In the offspring, haematological analysis and behavioural testing were performed during the postnatal stage. Our results revealed that predator stress causes an anxiety-like behaviour in dams along with a decrease in erythrocytes, a microcytosis, and a thrombocytosis. Prenatally stressed neonates manifested microcytosis and thrombocytosis with a significant polycythemia. Signs of motor hyperactivity, anxiety-like behaviour, and memory dysfunction were detected at periadolescence. Quercetin pretreatment alleviated the stress-induced behavioural and haematological impairments in dams but failed to attenuate the haematological changes in neonates. A sex-dependent effect of quercetin on behaviour was found at periadolescence. Our findings suggest that, besides a beneficial effect on haematological and behavioural anomalies in traumatized dams, quercetin may lastingly modulate the behaviour of their progeny. PMID:27240984

  8. 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

  9. Quercetin Inhibits Peripheral and Spinal Cord Nociceptive Mechanisms to Reduce Intense Acute Swimming-Induced Muscle Pain in Mice.

    PubMed

    Borghi, Sergio M; Pinho-Ribeiro, Felipe A; Fattori, Victor; Bussmann, Allan J C; Vignoli, Josiane A; Camilios-Neto, Doumit; Casagrande, Rubia; Verri, Waldiceu A

    2016-01-01

    The present study aimed to evaluate the effects of the flavonoid quercetin (3,3´,4´,5,7-pentahydroxyflavone) in a mice model of intense acute swimming-induced muscle pain, which resembles delayed onset muscle soreness. Quercetin intraperitoneal (i.p.) treatment dose-dependently reduced muscle mechanical hyperalgesia. Quercetin inhibited myeloperoxidase (MPO) and N-acetyl-β-D- glucosaminidase (NAG) activities, cytokine production, oxidative stress, cyclooxygenase-2 (COX-2) and gp91phox mRNA expression and muscle injury (creatinine kinase [CK] blood levels and myoblast determination protein [MyoD] mRNA expression) as well as inhibited NFκB activation and induced Nrf2 and HO-1 mRNA expression in the soleus muscle. Beyond inhibiting those peripheral effects, quercetin also inhibited spinal cord cytokine production, oxidative stress and glial cells activation (glial fibrillary acidic protein [GFAP] and ionized calcium-binding adapter molecule 1 [Iba-1] mRNA expression). Concluding, the present data demonstrate that quercetin is a potential molecule for the treatment of muscle pain conditions related to unaccustomed exercise. PMID:27583449

  10. HPLC Method for Simultaneous Quantitative Detection of Quercetin and Curcuminoids in Traditional Chinese Medicines

    PubMed Central

    Ang, Lee Fung; Yam, Mun Fei; Fung, Yvonne Tan Tze; Kiang, Peh Kok; Darwin, Yusrida

    2014-01-01

    Objectives: Quercetin and curcuminoids are important bioactive compounds found in many herbs. Previously reported high performance liquid chromatography ultraviolet (HPLC-UV) methods for the detection of quercetin and curcuminoids have several disadvantages, including unsatisfactory separation times and lack of validation according the standard guidelines of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. Methods: A rapid, specific, reversed phase, HPLC-UV method with an isocratic elution of acetonitrile and 2% v/v acetic acid (40% : 60% v/v) (pH 2.6) at a flow rate of 1.3 mL/minutes, a column temperature of 35°C, and ultraviolet (UV) detection at 370 nm was developed. The method was validated and applied to the quantification of different types of market available Chinese medicine extracts, pills and tablets. Results: The method allowed simultaneous determination of quercetin, bisdemethoxycurcumin, demethoxycurcumin and curcumin in the concentration ranges of 0.00488 ─ 200 μg/mL, 0.625 ─ 320 μg/mL, 0.07813 ─ 320 μg/mL and 0.03906 ─ 320 μg/mL, respectively. The limits of detection and quantification, respectively, were 0.00488 and 0.03906 μg/mL for quercetin, 0.62500 and 2.50000 μg/mL for bisdemethoxycurcumin, 0.07813 and 0.31250 μg/mL for demethoxycurcumin, and 0.03906 and 0.07813 μg/mL for curcumin. The percent relative intra day standard deviation (% RSD) values were 0.432 ─ 0.806 μg/mL, 0.576 ─ 0.723 μg/mL, 0.635 ─ 0.752 μg/mL and 0.655 ─ 0.732 μg/mL for quercetin, bisdemethoxycurcumin, demethoxycurcumin and curcumin, respectively, and those for intra day precision were 0.323 ─ 0.968 μg/mL, 0.805 ─ 0.854 μg/mL, 0.078 ─ 0.844 μg/mL and 0.275 ─ 0.829 μg/mL, respectively. The intra day accuracies were 99.589% ─ 100.821%, 98.588% ─ 101.084%, 9.289% ─ 100.88%, and 98.292% ─ 101.022% for quercetin, bisdemethoxycurcumin, demethoxycurcumin and

  11. Quercetin stabilizes apolipoprotein E and reduces brain Aβ levels in amyloid model mice.

    PubMed

    Zhang, Xilin; Hu, Jin; Zhong, Li; Wang, Na; Yang, Longyu; Liu, Chia-Chen; Li, Huifang; Wang, Xin; Zhou, Ying; Zhang, Yunwu; Xu, Huaxi; Bu, Guojun; Zhuang, Jiangxing

    2016-09-01

    Apolipoprotein E (apoE) is a major cholesterol carrier that regulates lipid homeostasis by mediating lipid transport from one tissue or cell type to another. In the central neural system (CNS), apoE is mainly produced by astrocytes, and transports cholesterol to neurons via apoE receptors, which are members of the low-density lipoprotein receptor family. The APOEε4 gene is a strong genetic risk factor for late-onset sporadic Alzheimer's disease (AD), likely through its strong effect on the accumulation of amyloid-β (Aβ) peptide. ApoE protein levels in cerebrospinal fluid (CSF) and plasma are reduced in APOEε4 carriers and in patients with AD. Furthermore, altered cholesterol levels are also associated with the risk of AD. Aβ accumulation, oligomerization and deposition in the brain are central to the pathogenesis of AD. Mounting evidence demonstrates that apoE and apoE receptors play important roles in these processes. Astrocyte-derived apoE is pivotal for cerebral cholesterol metabolism and clearance of Aβ. Thus, we hypothesized that increased apoE in the brain may be an effective therapeutic strategy for AD. We report here that quercetin can significantly increase apoE levels by inhibiting apoE degradation in immortalized astrocytes. Importantly, we show that oral administration of quercetin significantly increased brain apoE and reduced insoluble Aβ levels in the cortex of 5xFAD amyloid model mice. Our results demonstrate that quercetin increases apoE levels through a novel mechanism and can be explored as a novel class of drug for AD therapy. PMID:27114256

  12. Separation of (+)-catechin and quercetin on mesoporous MCM-41 composites: Dynamics of the sorption of flavonoids

    NASA Astrophysics Data System (ADS)

    Karpov, S. I.; Korabel'nikova, E. O.

    2015-06-01

    An analysis of conditions for chromatographic separation of quercetin and (+)-catechin based on experimental data and using the equations of an asymptotic model of sorption dynamics for substances characterized by convex isotherms of sorption is presented. The effects of the equilibrium (distribution coefficient) and kinetic (diffusion coefficient) factors on the dynamics of the sorption of flavonoids by ordered mesoporous material of the MCM-41 type and its composites with grafted organosilane groups is considered. The effects of kinetic and equilibrium parameters on the broadening of adsorption fronts is demonstrated with allowance for the inner and outer diffusion limitations of the sorption process.

  13. 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

  14. Quercetin exhibits a specific fluorescence in cellular milieu: a valuable tool for the study of its intracellular distribution.

    PubMed

    Nifli, Artemissia-Phoebe; Theodoropoulos, Panayiotis A; Munier, Sylvie; Castagnino, Chantal; Roussakis, Emmanuel; Katerinopoulos, Haralambos E; Vercauteren, Joseph; Castanas, Elias

    2007-04-18

    The elaboration of novel techniques for flavonoid intracellular tracing would elucidate the compounds' absorption and bioavailability and assist molecular and pharmacological approaches, as they are promising candidates for drug development. This study exploited the properties of quercetin (3,3',4',5,7-pentahydroxyflavone), found in high concentrations in the majority of edible plants. Through the use of UV-vis spectroscopy, confocal microscopy, and HPLC-ESI-MS, native quercetin, at physiologically relevant concentrations, was found to exhibit a specific fluorescence (488 nmex/500-540 nmem) upon internalization. This fluorescence shift is due to a non-covalent binding to intracellular targets (probably proteins) and compatible with the settings applied in confocal microscopy. This property provides a valuable, selective alternative technique for quercetin tracing in cellular systems, permitting the quantitative evaluation of its transit at pharmacologically relevant concentrations and the validation of a number of already described molecular functions. PMID:17385883

  15. Fabrication of Hollow Porous Silica Using a Combined Emulsion Sol-Gel Process and Amphiphilic Triblock Copolymer for Loading of Quercetin.

    PubMed

    Lee, Sang Gil; Kim, Young Ho; Bae, Jun Tae; Lee, Chung Hee; Pyo, Hyeong Bae; Kang, Kuk Hyoun; Lee, Dong Kyu

    2015-10-01

    Flavonoids have recently attracted significant interest as potential reducing agents, hydrogen-donating antioxidants, and singlet oxygen-quenchers. Quercetin, in particular, induces the expression of a gene, known to be associated with cell protection, in dose- and time-dependent manners. Therefore, quercetin may be used as an effective cosmeceutical material useful in the protection of dermal skin. In this study, hollow porous silica spheres used to load quercetin were prepared by using a combined emulsion sol-gel process and triblock copolymer as a template. Fabrication of hollow porous silica spheres was performed under various conditions such as the molar ratios of H2O/TEOS (Rw) and weight ratios of poloxamer 184/poloxamer 407. Loading of quercetin in hollow porous silica spheres was devised to improve the stability of quercetin and to consider the possibility as a raw cosmetic material. The surface of inclusion complexes of quercetin in hollow porous silicas was modified to enhance the stability of quercetin. The physicochemical properties of the samples were investigated using scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA)-differential thermal analysis (DTA) and Brunauer-Emmett-Teller (BET) surface area and porosity analysis. Determination of quercetin concentration was carried out by high-performance liquid chromatography (HPLC) analysis. PMID:26726443

  16. [Effect of quercetin on some indicators of the proteinase-proteinase inhibitor system in rats upon administration of cobalt chloride to them].

    PubMed

    Kaliman, P A; Samokhin, A A; Samokhina, L M

    2001-01-01

    The results of quercetin effect on some changes of proteinase--proteinase inhibitor system parameters in rats under cobalt chloride injection are shown. It was established that preliminary quercetin administration prevened neutral proteinase activation and alpha-2-macroglobulin activity decreasing after 2 h of cobalt chloride influence. PMID:12199071

  17. Quantitative Analysis of Vasodilatory Action of Quercetin on Intramural Coronary Resistance Arteries of the Rat In Vitro

    PubMed Central

    Monori-Kiss, Anna; Monos, Emil; Nádasy, György L.

    2014-01-01

    Background Dietary quercetin improves cardiovascular health, relaxes some vascular smooth muscle and has been demonstrated to serve as a substrate for the cyclooxygenase enzyme. Aims 1. To test quantitatively a potential direct vasodilatory effect on intramural coronary resistance artery segments, in different concentrations. 2. To scale vasorelaxation at different intraluminal pressure loads on such vessels of different size. 3. To test the potential role of prostanoids in vasodilatation induced by quercetin. Methods Coronary arterioles (70–240 µm) were prepared from 24 rats and pressurized in PSS, using a pressure microangiometer. Results The spontaneous tone that developed at 50 mmHg was relaxed by quercetin in the 10−9 moles/lit concentration (p<0.05), while 10−5 moles/lit caused full relaxation. Significant relaxation was observed at all pressure levels (10–100 mmHg) at 10−7 moles/lit concentration of quercetin. The cyclooxygenase blocker indomethacin (10−5moles/lit) induced no relaxation but contraction when physiological concentrations of quercetin were present in the tissue bath (p<0.02 with Anova), this contraction being more prominent in smaller vessels and in the higher pressure range (p<0.05, Pearson correlation). A further 2–8% contraction could be elicited by the NO blocker L-NAME (10−4 moles/lit). Conclusion These results demonstrate that circulating levels of quercetin (10−7 moles/lit) exhibit a substantial coronary vasodilatory effect. The extent of it is commeasurable with that of several other physiological mechanisms of coronary blood flow control. At least part of this relaxation is the result of an altered balance toward the production of endogenous vasodilatory prostanoids in the coronary arteriole wall. PMID:25144688

  18. 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

  19. 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

  20. 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

  1. Oral Delivery of a High Quercetin Payload Nanosized Emulsion: In Vitro and In Vivo Activity Against B16-F10 Melanoma.

    PubMed

    Dora, Cristiana Lima; Silva, Luis Felipe Costa; Mazzarino, Leticia; Siqueira, Jarbas Mota; Fernandes, Daniel; Pacheco, Leticia Kramer; Maioral, Mariana Franzoni; Santos-Silva, Maria Claudia; Baischl, Ana Luiza Muccillo; Assreuy, Jamil; Lemos-Senna, Elenara

    2016-02-01

    Quercetin is a natural compound that has several biological activities including anticancer activity. However, the use of this drug has been limited mostly because of its poor water solubility and low bioavailability. Therefore, the development of quercetin-loaded nanocarrier systems may be considered a promising advance to exploit its therapeutic properties in clinical setting including cancer treatment. This study evaluates the effect of orally administered nanosized emulsion containing quercetin (QU-NE) on the cytotoxicity activity against B16-F10 cells in vitro, and on subcutaneous melanoma in mice inoculated with B16-F1O cells. In vivo experiments, also evaluate the co-administration of quercetin with cisplatin in order to predict synergic effects and the renal and hepatic toxicity. The nanocarriers were prepared through the hot solvent diffusion associated with the phase inversion temperature methods. In vitro study showed reduction of cell viability in a concentration-depend manner for free quercetin and QU-NE. In vivo study, quercetin either as a free drug or colloidal dispersion was administrated at a dose of 5 mg kg(-1) twice a week for 17 days via oral route. Cisplatin was administrated at dose of 1 mg kg(-1) once a week intraperitoneally. Free quercetin and QU-NE reduced tumor growth, however, the reduction observed for QU-NE (P < 0.001 vs. control) was significantly higher than free quercetin (P < 0.05 vs. control). The association of both drugs did not show synergic effect. Besides, no renal or hepatic toxicities were observed after administration of free quercetin and QU-NE. These results suggest that an improvement in the oral bioavailability of quercetin occurred when this compound was dissolved in the oily phase of a nanosized emulsion, indicating that it might have a potential application in the treatment of melanoma. PMID:27433577

  2. The changes of antioxidant defense system caused by quercetin administration do not lead to DNA damage and apoptosis in the spleen and bone marrow cells of rats.

    PubMed

    Papiez, M A; Cierniak, A; Krzysciak, W; Bzowska, M; Taha, H M; Jozkowicz, A; Piskula, M

    2008-09-01

    Quercetin may have the opposite effect, namely anti- as well as pro-oxidant. The aim of this study was to assess the results of quercetin anti- and/or pro-oxidant activity in the bone marrow and spleen cells of rats. The experimental rats were treated daily, with quercetin in a dose of 8 or 80mg/kg b.w. by gavage for 40 days. The intracellular redox state in cells were assessed by measuring the ferric ion reducing antioxidant power (FRAP) level and malonodialdehyde concentration. HO-1 mRNA expression was examined with real-time PCR. The extent of DNA damage was determined by the alkaline-labile comet assay. A potential pro-apoptotic quercetin action was determined using the FITC-Annexin V kit. The quercetin and isorhamnetin concentrations in serum were analyzed by HPLC-ECD. MDA concentration and FRAP values, were significantly decreased in the spleen and bone marrow cells of rats treated with quercetin, in a dose of 80mg/kg b.w. in comparison with the control rats; no significant changes were observed after quercetin was administered in a dose ten times as low. Treatment with quercetin dose-dependently upregulated the expression of HO-1 mRNA in the bone marrow cells. Quercetin administration to the rats did not induce either DNA damage or apoptosis in the examined cells. The results of our study prove that changes in the antioxidant state, caused by quercetin, do not lead to DNA damage or exert any pro-apoptotic activity in vivo. PMID:18602965

  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

    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

  4. 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.

  5. Synergistic Effect of the Flavonoid Catechin, Quercetin, or Epigallocatechin Gallate with Fluconazole Induces Apoptosis in Candida tropicalis Resistant to Fluconazole

    PubMed Central

    da Silva, Cecília Rocha; de Andrade Neto, João Batista; de Sousa Campos, Rosana; Figueiredo, Narjara Silvestre; Sampaio, Letícia Serpa; Magalhães, Hemerson Iury Ferreira; Cavalcanti, Bruno Coêlho; Gaspar, Danielle Macêdo; de Andrade, Geanne Matos; Lima, Iri Sandro Pampolha; de Barros Viana, Glauce Socorro; de Moraes, Manoel Odorico; Lobo, Marina Duarte Pinto; Grangeiro, Thalles Barbosa

    2014-01-01

    Flavonoids are a class of phenolic compounds commonly found in fruits, vegetables, grains, flowers, tea, and wine. They differ in their chemical structures and characteristics. Such compounds show various biological functions and have antioxidant, antimicrobial, anti-inflammatory, and antiapoptotic properties. The aim of this study was to evaluate the in vitro interactions of flavonoids with fluconazole against Candida tropicalis strains resistant to fluconazole, investigating the mechanism of synergism. Three combinations formed by the flavonoids (+)-catechin hydrated, hydrated quercetin, and (−)-epigallocatechin gallate at a fixed concentration with fluconazole were tested. Flavonoids alone had no antifungal activity within the concentration range tested, but when they were used as a cotreatment with fluconazole, there was significant synergistic activity. From this result, we set out to evaluate the possible mechanisms of cell death involved in this synergism. Isolated flavonoids did not induce morphological changes or changes in membrane integrity in the strains tested, but when they were used as a cotreatment with fluconazole, these changes were quite significant. When evaluating mitochondrial damage and the production of reactive oxygen species (ROS) only in the cotreatment, changes were observed. Flavonoids combined with fluconazole were shown to cause a significant increase in the rate of damage and the frequency of DNA damage in the tested strains. The cotreatment also induced an increase in the externalization of phosphatidylserine, an important marker of early apoptosis. It is concluded that flavonoids, when combined with fluconazole, show activity against strains of C. tropicalis resistant to fluconazole, promoting apoptosis by exposure of phosphatidylserine in the plasma membrane and morphological changes, mitochondrial depolarization, intracellular accumulation of ROS, condensation, and DNA fragmentation. PMID:24366745

  6. Computational Study of Catalytic Reaction of Quercetin 2,4-Dioxygenase.

    PubMed

    Saito, Toru; Kawakami, Takashi; Yamanaka, Shusuke; Okumura, Mitsutaka

    2015-06-11

    We present a quantum mechanics/molecular mechanics (QM/MM) and QM-only study on the oxidative ring-cleaving reaction of quercetin catalyzed by quercetin 2,4-dioxygenase (2,4-QD). 2,4-QD has a mononuclear type 2 copper center and incorporates two oxygen atoms at C2 and C4 positions of the substrate. It has not been clear whether dioxygen reacts with a copper ion or a substrate radical as the first step. We have found that dioxygen is more likely to bind to a Cu(2+) ion, involving the dissociation of the substrate from the copper ion. Then a Cu(2+)-alkylperoxo complex can be generated. Comparison of geometry and stability between QM-only and QM/MM results strongly indicates that steric effects of the protein environment contribute to maintain the orientation of the substrate dissociated from the copper center. The present QM/MM results also highlight that a prior rearrangement of the Cu(2+)-alkylperoxo complex and a subsequent hydrogen bond switching assisted by the movement of Glu73 can facilitate formation of an endoperoxide intermediate selectively. PMID:25990020

  7. Synthesis and testing of novel isomeric mitochondriotropic derivatives of resveratrol and quercetin.

    PubMed

    Biasutto, Lucia; Mattarei, Andrea; Paradisi, Cristina

    2015-01-01

    We report here the synthetic procedures to obtain mitochondria-targeted resveratrol and quercetin derivatives. These two compounds were selected among plant polyphenols because both are well studied and have many health-promoting actions. The synthetic strategies reported here are however expected to be adaptable to other polyphenols with similar reactivity at the phenolic hydroxyls.Mitochondrial targeting can be achieved by incorporating in the molecule an "electrophoretic" membrane-permeant, triphenylphosphonium cation. We have generally chosen to link it via a butyl spacer forming an ether bond with one of the phenolic oxygens. The first step toward the synthesis of all mitochondriotropic derivatives described in this work is the production of a regiospecific -(4-O-chlorobutyl) derivative. Triphenylphosphonium (P(+)Ph3I(-)) is then introduced through two consecutive nucleophilic substitution steps: -Cl→-I→-P(+)Ph3I(-). Pure mono-substituted chlorobutyl regioisomers are obtained by purification from the reaction mixture in the case of resveratrol, while specific protection strategies are required for quercetin to favor alkylation of one specific hydroxyl.Physicochemical properties of the derivatives (i.e., water solubility, affinity for cell membranes) can be furthermore modulated by functionalization of the remaining hydroxyls; we report here synthetic protocols to obtain acetylated and methylated analogs.We also briefly describe how to assess mitochondrial accumulation of the derivatives; the proposed techniques are the use of a TPP(+)-selective electrode (with isolated rat liver mitochondria) and fluorescence microscopy (with cultured cells). PMID:25634275

  8. Quercetin as a finer substitute to aminoguanidine in the inhibition of glycation products.

    PubMed

    Ashraf, Jalaluddin M; Shahab, Uzma; Tabrez, Shams; Lee, Eun Ju; Choi, Inho; Ahmad, Saheem

    2015-01-01

    Non-enzymatic glycation is the addition of a free carbonyl group of a reducing sugar to the free amino groups of proteins, which results in the formation of early and advanced glycation end-products (AGEs). Glycation reaction is profoundly associated with diabetes and its secondary complications, such as nephropathy and neuropathy. Glyoxal is a carbonyl species that reacts rapidly with the free amino groups of proteins to form AGEs. While the formation of AGEs with various glycating agents has previously been demonstrated, no extensive studies have been conducted to assess the role of quercetin in all three stages of glycation (early, intermediate and late). In this study, we report the glycation of HSA (human serum albumin) and its characterization by several spectroscopic techniques. Furthermore, inhibition of products at all stages of glycation was studied by various assays. Spectroscopic analysis suggests structural perturbations in the HSA macromolecule as a result of modification, which might be due to the generation of free radicals and the formation of AGEs. Inhibition in the formation of glycation has established that quercetin is a better and a more potent antiglycating agent than aminoguanidine at all stages of glycation. PMID:25799884

  9. Ab initio molecular dynamics of the reaction of quercetin with superoxide radical

    NASA Astrophysics Data System (ADS)

    Lespade, Laure

    2016-08-01

    Superoxide plays an important role in biology but in unregulated concentrations it is implicated in a lot of diseases such as cancer or atherosclerosis. Antioxidants like flavonoids are abundant in plant and are good scavengers of superoxide radical. The modeling of superoxide scavenging by flavonoids from the diet still remains a challenge. In this study, ab initio molecular dynamics of the reaction of the flavonoid quercetin toward superoxide radical has been carried out using Car-Parrinello density functional theory. The study has proven different reactant solvation by modifying the number of water molecules surrounding superoxide. The reaction consists in the gift of a hydrogen atom of one of the hydroxyl groups of quercetin to the radical. When it occurs, it is relatively fast, lower than 100 fs. Calculations show that it depends largely on the environment of the hydroxyl group giving its hydrogen atom, the geometry of the first water layer and the presence of a certain number of water molecules in the second layer, indicating a great influence of the solvent on the reactivity.

  10. Quercetin and epigallocatechin-3-gallate effect on the anisotropy of model membranes with cholesterol.

    PubMed

    Ionescu, Diana; Margină, Denisa; Ilie, Mihaela; Iftime, Adrian; Ganea, Constanţa

    2013-11-01

    Cell membrane fluidity, which can be altered by oxidative stress, plays an important role in the cell physiology. Flavonoids are among the most studied food substances that prevent and/or reduce oxidative stress, but their action mechanisms are far from being understood. We performed a study on the effect of quercetin and epigallocatechin-3-gallate on 2-Dimyristoyl-sn-glycero-3-phosphocholine small unilamellar vesicles (SUVs) with different amounts of cholesterol, using Laurdan as a fluorescent probe, to put into evidence the perturbations of the phospholipid membrane fluidity and local lipid order in an attempt to decipher the action mechanism of the flavonoids at the cell membrane level. Results indicate that polyphenols modulate the transition from the gel phase to the liquid crystalline phase of SUVs in all studied membranes. SUVs with cholesterol have by themselves higher phase transition temperature and the presence of polyphenols stabilizes further the membrane. Quercetin has a dose-dependent effect on the fluidity and local order of the lipid membranes, whilst epigallocatechin-3-gallate action is not dose-dependent, the differences being attributable to the hydrophobic/hydrophilic character of the substances. The findings are discussed within the frame of earlier reports on the effect of polyphenols on artificial membranes. PMID:23523830

  11. Nanoparticle Based Delivery of Quercetin for the Treatment of Carbon Tetrachloride Mediated Liver Cirrhosis in Rats.

    PubMed

    Verma, Shashi Kant; Rastogil, Shweta; Arora, Indu; Javed, Kalim; Akhtar, Mohd; Samim, Mohd

    2016-02-01

    Liver fibrosis is the common response to chronic liver injury and ultimately leads to cirrhosis. There is a pressing need in the pharmaceutical industry to develop efficient well-targeted drug delivery systems, which are lacking to date. This study was designed to investigate the efficacy of a nanoquercetin NQ; i.e., quercetin encapsulated in PAG (p-aminophenyl-1-thio-β-D-galactopryranoside)-coated NIPAAM (N-isopropyl acrylamide) nanopolymer in liver compared with naked quercetin (Q) using a carbon tetrachloride (CCl₄)-mediated liver cirrhosis model. NQ was more effective at restoring liver membrane integrity as indicated by significantly reduced serum markers, including Alanine Transaminase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) and Lactate Dehydrogenase (LDH), compared with naked Q. The findings of reduced collagen and histopathology also show that the NQ effects were much better than those of naked Q. Biochemical parameters, including antioxidant defense enzymes, also provide supporting evidence. Furthermore, the decrease in NF-κB and NOS-2 expression in the NQ-treated groups was also much stronger than in the naked Q-treated group. Thus, the data clearly suggest that NQ not only provides significant hepatoprotection compared with naked Q, but it also substantially lowered the required concentration (1,000 to 10,000-fold lower) by increasing the bioavailability. PMID:27305761

  12. Supplemental genistein, quercetin, and resveratrol intake in active duty army soldiers.

    PubMed

    Sepowitz, John J; Fauser, Kristina R; Meyer, Stephanie A; Jackson, Steven J

    2015-05-01

    Previous reports indicate that the majority of U.S. Army soldiers consume dietary supplements (DSs) > 1 time/wk. However, these studies did not evaluate phytonutrient supplementation. A growing literature suggests inclusion of phytonutrients in DSs may pose a risk for toxicity, which could impact the performance of soldier duties, as well as long-term health and wellness. This study was conducted to assess and understand soldiers' motivations to consume phytonutrient-containing DSs, specifically genistein, quercetin, and resveratrol. The study was a cross-sectional, descriptive mixed-methods design using a survey and semistructured interviews. There were 436 soldiers stationed at Joint Base Lewis-McChord, Washington who completed the survey, from which 36 soldiers completed an interview. Overall, 34% of soldiers reported taking a single or multicomponent phytonutrient DS > 1 time/wk, from which 41 soldiers took >1 supplement/wk. Soldiers' reasons for use included unsure (54%), weight loss (12%), and other, unspecified (24%). The majority of interviewees did not consume DSs based on inclusion of genistein, quercetin, or resveratrol. The majority of soldiers, in our study, appear unable to rationalize their phytonutrient DS choices. Findings from this study illuminate the need for future research to further explore DS practices within military populations and encourage informed use of DSs. PMID:25939109

  13. 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

  14. Efficacy of quercetin against chemically induced murine oral squamous cell carcinoma

    PubMed Central

    DROGUETT, DANIEL; CASTILLO, CHRISTIAN; LEIVA, ELBA; THEODULOZ, CRISTINA; SCHMEDA-HIRSCHMANN, GUILLERMO; KEMMERLING, ULRIKE

    2015-01-01

    Oral squamous cell carcinoma (OSCC) is the most common form of head and neck cancer, and oxidative damage is associated with the development of OSCCs. Antioxidants have therefore been proposed for use as chemoprotective agents against different types of cancer. In the present study, the effect of the antioxidant quercetin, administered at doses of 10 and 100 mg/kg/day, was investigated in an experimental murine model of 4-nitroquinoline 1-oxide (4-NQO)-induced carcinogenesis. The survival of the treated animals, the plasmatic levels of reduced glutathione and the type and severity of lesions (according the International Histological Classification of Tumors and Bryne's Multifactorial Grading System for the Invasive Tumor Front) were assessed. Additionally, the organization of the extracellular matrix was analyzed by carbohydrate and collagen histochemistry, and immunohistochemistry was used to assess the expression of the tumor markers proliferating cell nuclear antigen and mutated p53. The results indicate that, despite the promising effect of quercetin in other studies, this drug is ineffective as a chemoprotective agent against 4-NQO-induced OSCC in mice at the assayed doses. PMID:26622865

  15. The flavonols quercetin, rutin and morin in DNA solution: UV-vis dichroic (and mid-infrared) analysis explain the possible association between the biopolymer and a nucleophilic vegetable-dye.

    PubMed

    Solimani, R

    1997-08-29

    Previous studies showed evidence that quercetin can bind DNA by intercalation [R. Solimani et al., J. Agric. Food Chem. 43 (1995) 876-882] and a comparison with the flavanol dihydroquercetin indicated that the interaction is correlated to the planarity and hydrophobicity of the benzopyranic-4-one plane [R. Solimani, Int. J. Biol. Macromol. 18 (1996) 287-295]. In this study flow linear dichroism (LD) spectra of the hydrophobic quercetin were compared with hydrophilic aglycoside morin and 3-glycoside rutin in the same conditions: [DNA] = 3.1 x 10(-2) mol/l phosphate, [dye] = (1.0-4.0) x 10(-4) mol/l. Morin and rutin in an aqueous environment showed the same behaviour as quercetin in buffer-ethanol (70:30, v/v) solution, with their common benzopyranic-4-one part within the biopolymer. The LD(R) values (LD normalised to the relative isotropic absorption) indicated a greater affinity of the quercetin for the DNA. Comparison of the LD(R) of morin and rutin showed a ratio LD(R)morin/LD(R)rutin approximately 1.1-1.2 very close to unity and this suggests the localisation of the 3-rutinoside of rutin outside the intercalation site. Dichroic measurements recorded in extreme conditions of concentration partly clarified the sequences of interaction between quercetin and DNA in solution which shows the prototypical behaviour of the flavonolic group. This consists of an initial weak external association, where an electrostatic component is excluded, and which can evolve to intercalation changing the DNA concentration, whereas the quantity of the flavonol influences relatively the association. The carbonylic region of the benzopyranic-4-one chromophore is probably localised outside the intercalation site. This was suggested by indirect infrared (attenuated total reflection ATR) data of the quercetin-ethanol solution: the presence of free and chelated carbonyl determines a greater density of negative charges in this region of the chromophore, with the consequent lower probability

  16. A quercetin-modified biosensor for amperometric determination of uric acid in the presence of ascorbic acid.

    PubMed

    He, Jian-Bo; Jin, Guan-Ping; Chen, Qun-Zhi; Wang, Yan

    2007-03-01

    The present work reports a quercetin-modified wax-impregnated graphite electrode (Qu/WGE) prepared through an electrochemical oxidation procedure in quercetin-containing phosphate buffer solution (PBS), for the purpose of detecting uric acid (UA) in the presence of ascorbic acid (AA). During modification quercetin was oxidized to the corresponding quinonic structure, and in the blank buffer solution the electrodeposited film exhibits a voltammetric response anticipated for the surface-immobilized quercetin. Retarding effect of the film towards the reaction of anionic species was found; therefore the pH of sample solutions was selected to ensure the analyte in molecular form. At suitable pHs the Qu/WGE shows excellent electrocatalytic effect towards the oxidation of both AA and UA, and separates the voltammetric signal of UA from AA by about 280 mV, allowing simultaneous detection of these two species. A linear relation between the peak current and concentration was obtained for UA in the range of 1-50 microM in the presence of 0.5 mM AA, with a detection limit 1.0 microM (S/N=3). This sensor was stable, reproducible and outstanding for long-term use. PMID:17386683

  17. Effects of Quercetin on CYP450 and Cytokines in Aroclor 1254 Injured Endometrial Cells of the Pregnant Rats

    PubMed Central

    Xu, Lina; Sun, Liyun; Lu, Liqin; Qin, Jianhua

    2014-01-01

    Polychlorinated biphenyls (PCBs) are widespread persistent residual environmental pollutants, which affect seriously the growth and reproductive alterations in humans and animals. Aroclor 1254 is a commercial mixture of PCBs. Quercetin is a flavonoid, which acts on estrogen receptors and causes the development of estrogen-related diseases. In this paper, the primary cultured endometrial cells in the pregnant rats were isolated and Aroclor 1254 was used to induce the injured endometrial cells model. The cells were treated with gradient quercetin, the viability of the endometrial cells, the expressions of CYP450, the contents of TNF-α, IL-6, estradiol (E2), and progesterone (P4) were measured. It showed that the viability of the cultured endometrial cells, the expression of CYP1A1 and CYP2B1, and the contents of TNF-α, E2, and IL-6 in the injured endometrial cells increased with the treatment of quercetin. It shows that quercetin has protective effect on the injured endometrial cells in the pregnant rats, this provide a basis on herbal medicine protection for animal reproductive diseases caused by environmental endocrine disruptors. PMID:24711995

  18. Quercetin modulates NF-kappa B and AP-1/JNK pathways to induce cell death in human hepatoma cells.

    PubMed

    Granado-Serrano, Ana Belén; Martín, María Angeles; Bravo, Laura; Goya, Luis; Ramos, Sonia

    2010-01-01

    Quercetin, a dietary flavonoid, has been shown to possess anticarcinogenic properties, but the precise molecular mechanisms of action are not thoroughly elucidated. The aim of this study was to investigate the regulatory effect of quercetin (50 microM) on two main transcription factors (NF-kappa B and AP-1) related to survival/proliferation pathways in a human hepatoma cell line (HepG2) over time. Quercetin induced a significant time-dependent inactivation of the NF-kappa B pathway consistent with a downregulation of the NF-kappa B binding activity (from 15 min onward). These features were in concert with a time-dependent activation (starting at 15 min and maintained up to 18 h) of the AP-1/JNK pathway, which played an important role in the control of the cell death induced by the flavonoid and contributed to the regulation of survival/proliferation (AKT, ERK) and death (caspase-3, p38, unbalance of Bcl-2 proapoptotic and antiapoptotic proteins) signals. These data suggest that NF-kappa B and AP-1 play a main role in the tight regulation of survival/proliferation pathways exerted by quercetin and that the sustained JNK/AP-1 activation and inhibition of NF-kappa B provoked by the flavonoid induced HepG2 death. PMID:20358477

  19. Concomitant Intake of Quercetin with a Grain-Based Diet Acutely Lowers Postprandial Plasma Glucose and Lipid Concentrations in Pigs

    PubMed Central

    Wein, Silvia; Wolffram, Siegfried

    2014-01-01

    Treatment goals of diabetes mellitus type 2 (DMT2) include glycemic control and reduction of nonglycemic risk factors, for example, dyslipidemia. Quercetin, a plant-derived polyphenol, often discussed for possible antidiabetic effects, was investigated for acute postprandial glucose- and lipid-lowering effects in healthy growing pigs. Male pigs (n = 16, body weight = BW 25–30 kg) were fed flavonoid-poor grain-based meals without (GBM) or with quercetin (GBMQ). In a first experiment, postprandial plasma concentrations of glucose, nonesterified fatty acids (NEFA), and triacylglycerols were analyzed in 8 pigs receiving 500 g of either GBM or GBMQ (10 mg/kg BW) in a cross-over design. Blood samples were collected before, and up to 5 h every 30 min, as well as 6 and 8 h after the feeding. In the second experiment, 2 h after ingestions of 1000 g of either GBM or GBMQ (50 mg/kg BW) animals were sacrificed; gastric content was collected and analyzed for dry matter content. Quercetin ingestion reduced postprandial glucose, NEFA, and TG concentration, but two hours after ingestion of the meal no effect on gastric emptying was observed. Our results point to inhibitory effects of quercetin on nutrient absorption, which appear not to be attributable to delayed gastric emptying. PMID:24847478

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

    PubMed

    Li, Hongbo; Xue, Yan; Wang, Wei

    2014-04-15

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

  1. Route of administration determines the anxiolytic activity of the flavonols kaempferol, quercetin and myricetin--are they prodrugs?

    PubMed

    Vissiennon, Cica; Nieber, Karen; Kelber, Olaf; Butterweck, Veronika

    2012-07-01

    Several in vivo and in vitro studies have confirmed that flavonols are metabolized by the intestinal microflora to their corresponding hydroxyphenylacetic acids. In this article, a comparison of the anxiolytic activity of the flavonols kaempferol, quercetin and myricetin in the elevated plus maze after oral (po) and intraperitoneal (ip) administration to mice in a dose range of 0.1 to 2.0 mg/kg is presented. In addition, their corresponding metabolites p-hydroxyphenylacetic acid (p-HPAA) and 3,4-dihydroxyphenylacetic acid (DOPAC) were tested after intraperitoneal administration. Anxiolytic activity was detected for kaempferol and quercetin only after oral administration. No anxiolytic effects were observed when kaempferol and quercetin were given via the intraperitoneal administration route. The corresponding hydroxyphenylacetic metabolites p-HPAA and DOPAC showed anxiolytic effects after intraperitoneal application. In order to further test the hypothesis that flavonoids are possible prodrugs which require activation by intestinal bacteria, gut sterilization was performed using pretreatment with the antibiotic enrofloxacin (7.5 mg/day, po, for 4 days). After antibiotic treatment, the anxiolytic effect of kaempferol and quercetin disappeared, whereas it was still present for the positive control diazepam. Our results support the hypothesis that flavonoids act as prodrugs which are transformed into their active hydroxyphenylacetic acid metabolites by intestinal microflora. PMID:21840194

  2. Antibiofouling potential of quercetin compound from marine-derived actinobacterium, Streptomyces fradiae PE7 and its characterization.

    PubMed

    Gopikrishnan, Venugopal; Radhakrishnan, Manikkam; Shanmugasundaram, Thangavel; Pazhanimurugan, Raasaiyah; Balagurunathan, Ramasamy

    2016-07-01

    An attempt has been made to isolate, purify and characterize antifouling compound from Streptomyces fradiae PE7 isolated from Vellar estuarine sediment, Parangipettai, South India. The microbial identification was done at species level based on its phenotypic, cell wall and molecular characteristics. Strain PE7 produced high quantity of antifouling compounds in agar surface fermentation when compared to submerged fermentation. In fermentation optimization, wide range of sugars, amino acids, minerals, pH, temperature and NaCl concentration was found to influence the antifouling compound production from the strain PE7. Antifouling compound PE7-C was purified from the crude extract by preparative TLC, and its activity against biofouling bacteria was confirmed by bioautography. Based on the physico-chemical characteristics, the chemical structure of the antifouling compound PE7-C was identified as quercetin (C15H10O7), a flavonoid class of compound with the molecular weight 302.23 g/mol. The purified quercetin was active against 18 biofouling bacteria with MIC range between 1.6 and 25 μg/ml, algal spore germination and mollusc foot adherence found at 100 μg/ml and 306 ± 19.6 μg ml(-1) respectively. The present study, for the first time, reported quercetin from marine-derived Streptomyces sp. PE7 with antifouling activity. This also leads to the repurposing of quercetin for the development of antifouling agent. PMID:27032633

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

    PubMed Central

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

    2016-01-01

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

  4. 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

  5. Quercetin lowers plasma uric acid in pre-hyperuricaemic males: a randomised, double-blinded, placebo-controlled, cross-over trial.

    PubMed

    Shi, Yuanlu; Williamson, Gary

    2016-03-14

    Elevated plasma uric acid concentration is a risk factor for gout, insulin resistance and type 2 diabetes. Quercetin, a flavonoid found in high levels in onions, tea and apples, inhibits xanthine oxidoreductase in vitro, the final step in intracellular uric acid production, indicating that quercetin might be able to lower blood uric acid in humans. We determined the effects of 4 weeks of oral supplementation of quercetin on plasma uric acid, blood pressure and fasting glucose. This randomised, double-blinded, placebo-controlled, cross-over trial recruited twenty-two healthy males (19-60 years) with baseline plasma uric acid concentration in the higher, but still considered healthy, range (339 (SD 51) µmol/l). The intervention included one tablet containing 500 mg quercetin daily for 4 weeks, compared with placebo, with a 4-week washout period between treatments. The primary outcome was change in concentrations of plasma uric acid after 2 and 4 weeks; secondary outcome measures were changes in fasting plasma glucose, 24-h urinary excretion of uric acid and resting blood pressure. After quercetin treatment, plasma uric acid concentrations were significantly lowered by -26·5 µmol/l (95% CI, -7·6, -45·5; P=0·008), without affecting fasting glucose, urinary excretion of uric acid or blood pressure. Daily supplementation of 500 mg quercetin, containing the bioavailable amount of quercetin as present in approximately 100 g red onions, for 4 weeks, significantly reduces elevated plasma uric acid concentrations in healthy males. PMID:26785820

  6. Competitive interactions and controlled release of a natural antioxidant from halloysite nanotubes.

    PubMed

    Hári, József; Gyürki, Ádám; Sárközi, Márk; Földes, Enikő; Pukánszky, Béla

    2016-01-15

    Halloysite nanotubes used as potential carrier material for a controlled release stabilizer in polyethylene were thoroughly characterized with several techniques including the measurement of specific surface area, pore volume and surface energy. The high surface energy of the halloysite results in the strong bonding of the additive to the surface. Dissolution experiments carried out with eight different solvents for the determination of the effect of solvent characteristics on the amount of irreversibly bonded quercetin proved that adsorption and dissolution depend on competitive interactions prevailing in the system. Solvents with low polarity dissolve only surplus quercetin adsorbed in multilayers. Polyethylene is a very apolar polymer forming weak interactions with every substance; quercetin dissolves into it from the halloysite surface only above a critical surface coverage. Stabilization experiments confirmed that strong adhesion prevents dissolution and results in limited stabilization efficiency. At larger adsorbed amounts better stability and extended effect were measured indicating dissolution and controlled release. PMID:26454181

  7. Cadmium exposure during lactation causes learning and memory-impairment in F1 generation mice: amelioration by quercetin.

    PubMed

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

    2016-07-01

    Cadmium (Cd) is a known pollutant present in the environment at low levels and is reported to affect reproduction in many ways. The present study was undertaken to explore the effect of Cd in F1 generation mice on cognitive parameters, and to further investigate whether quercetin could modulate these effects. In this study, female lactating mice were exposed to cadmium for seven days just after delivery. The new born pups in their adulthood were tested for learning and memory parameters by passive avoidance task and Morris water maze (MWM) test. It was observed that pups exposed to Cd showed significant impairment of memory in step down latency test, which was reversed by quercetin (100 mg/kg). In MWM test for spatial memory, animals exposed to Cd exhibited increased escape latency, which was reversed by quercetin (50 mg/kg) significantly. Quercetin alone (50 and 100 mg/kg) also demonstrated improved spatial memory, and showed improved retention memory in the passive avoidance paradigm at dose 50 mg/kg. On testing oxidative stress parameters, we observed significantly increased malondialdehyde (MDA) levels in brain tissue of Cd-treated mice. Moreover, co-treatment with quercetin (50 mg/kg) and Cd significantly reduced these MDA levels. The other doses (25 and 100 mg/kg) also showed reduction in MDA levels as compared to the group exposed to Cd alone, though the difference was not statistically significant. Hence, this study highlights the possibility of cognitive impairment in adulthood if there is Cd exposure during lactation and oxidative stress could possibly attribute to this effect. PMID:26446883

  8. Reversion of Asthmatic Complications and Mast Cell Signalling Pathways in BALB/c Mice Model Using Quercetin Nanocrystals.

    PubMed

    Gupta, Kriti; Kumar, Sandeep; Gupta, Rinkesh Kumar; Sharma, Akanksha; Verma, Alok K; Stalin, K; Chaudhari, Bhushan P; Das, Mukul; Singh, Surinder P; Dwivedi, Premendra D

    2016-04-01

    The tranquillizing effects of quercetin on allergic asthma are promising, but its poor water solubility and bioavailability is still a bottleneck. In this study, an ovalbumin (OVA) sensitized BALB/c mice asthma model was used to investigate the potential of quercetin nanocrystals (nQ) on relieving asthma aggravation. The water soluble nQ was prepared by the homogenization using the high energy sonication method. X-ray diffraction data showed the formation of nQ (10-30 nm) which was in agreement with transmission electron microscopy. The nQ was found to be more stable and soluble in PBS, and sera of BALB/c mice compared to bulk quercetin. Dose dependent experiments with nQ on OVA sensitized asthma mice exhibited significant anti-asthmatic potential of nQ at much lower dose (1 mg/kg body weight) compared to bulk quercetin. The treatment of nQ remarkably resulted in reduced OVA specific immunoglobulin E (sIgE) production, anaphylaxis signs and type 1 skin test. The nQ also significantly modulated the expression of Th2 cytokines like IL-4 and IL-5, which are responsible for IgE class switching and suppressed the degranulation/secretion of different chemical mediators (PGD2, mMCPT-1 Cys-L and TSLP) from activated mast cells. The levels of FcεR1, Syk, c-Yes, PI-3, p-PI-3, PLC-γ2, and p-PLC-γ2 were found to be reduced in the OVA sensitized BALB/c mice treated with nQ compared to those treated with OVA only. The results indicate that nQ alleviate pulmonary inflammation and airway hyporesponsiveness in allergic asthma at much lower dose compared to bulk quercetin and may be considered as a potential drug for the treatment of asthmatic patients. PMID:27301198

  9. [Determination of rutin, quercetin and kaempferol in Althaea rosea (L) Gavan for Uyghur medicine by high performance liquid chromatography].

    PubMed

    Muhetaer, Tu'erhong; Resalat, Yimin; Chu, Ganghui; Yin, Xuebo; Munira, Abudukeremu

    2015-12-01

    Uyghur medicine is one important part of the national medicine system. Uyghur medicine modernization, namely the study of effective components with modern technologies, is the only way for the scientification, standardization, and industrialization of Uyghur medicine. Here we developed a selective extraction method for rutin, quercetin and kaempferol in Althaea rosea (L) Gavan. The three active species were determined by high performance liquid chromatography (HPLC) with HC-C18 column (250 mm x 4.6 mm, 5 μm) and the mobile phase of CH3OH-0.4% H3PO4 (50 :50, v/v). Rutin, quercetin and kaempferol were baseline separated with each other and the interference species with flow rate of 1.0 mL/min and column temperature of 30 degrees C. Under the optimal conditions, linear correlation were obtained in the mass concentration range of 12.5-150 μg/mL (r = 0.999 8) for rutin, 12.5-125 μg/mL (r = 0.999 9) for quercetin, and 12.5-125 μg/mL (r = 0.998 8) for kaempferol. The recoveries (n = 5) of rutin, quercetin and kaempferol were 100.25% ( RSD = 1.1%), 97.60% ( RSD = 0.47%) and 97.75% (RSD = 0.71%), respectively. The method can be used to determine the contents of rutin, quercetin and kaempferol in Althaea rosea (L) Gavan and provide the guidance for the analysis of the flavonoids in other Uyghur medicines. PMID:27097460

  10. The Dietary Bioflavonoid, Quercetin, Selectively Induces Apoptosis of Prostate Cancer Cells by Down-Regulating the Expression of Heat Shock Protein 90

    PubMed Central

    Aalinkeel, Ravikumar; Bindukumar, B.; Reynolds, Jessica L.; Sykes, Donald E.; Mahajan, Supriya D.; Chadha, Kailash C.; Schwartz, Stanley A.

    2010-01-01

    BACKGROUND Human and animal studies have suggested that diet-derived flavonoids, in particular quercetin may play a beneficial role by preventing or inhibiting oncogenesis, but the underlying mechanism remains unclear. The aim of this study is to evaluate the effect(s) of quercetin on normal and malignant prostate cells and to identify the target(s) of quercetin’s action. METHODOLOGY We addressed this question using cells in culture and investigated whether quercetin affects key biological processes responsible for tumor cell properties such as cell proliferation and apoptosis and also studied the effect of quercetin on the proteome of prostate cancer cells using difference gel electrophoresis (DIGE) to assess changes in the expression of relevant proteins. RESULTS Our findings demonstrate that quercetin treatment of prostate cancer cells results in decreased cell proliferation and viability. Furthermore, we demonstrate that quercetin promotes cancer cell apoptosis by down-regulating the levels of heat shock protein (Hsp) 90. Depletion of Hsp90 by quercetin results in decreased cell viability, levels of surrogate markers of Hsp90 inhibition (intracellular and secreted), induced apoptosis and activation of caspases in cancer cells but not in normal prostate epithelial cells. Knockdown of Hsp90 by short interfering RNA also resulted in induction apoptosis similar to quercetin in cancer cells as indicated by annexin V staining. CONCLUSION Our results demonstrate that quercetin down-regulates the expression of Hsp90 which, in turn, induces inhibition of growth and cell death in prostate cancer cells while exerting no quantifiable effect on normal prostate epithelial cells. PMID:18726985

  11. 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

  12. Toxicology and Carcinogenesis Studies of Quercetin (CAS No. 117-39-5) in F344 Rats (Feed Studies).

    PubMed

    1992-09-01

    Quercetin is a member of a group of naturally occurring compounds, the flavonoids, which have a common flavone nucleus composed of two benzene rings linked through a heterocyclicpyrone ring. Quercetin is found in various plants, food products, and dyes of natural origin. The estimated average daily intake of quercetin by an individual in the United States is 25 mg. The Food and Drug Administration nominated quercetin for toxicity and carcinogenicity studies in the rat because it is a chemical that is widely distributed in foods. Quercetin was administered to rats by dosed feed since human exposure is by dietary consumption. Information in the literature showed that quercetin administered in the diet to rats at levels up to approximately 4% caused a minor body weight effect, whereas higher dose levels produced greater than 10% reduction in body weight gains relative to controls. Based on this information, the NTP 2-year studies were conducted by administering 0, 1,000, 10,000, or 40,000 ppm quercetin (>95% pure) in feed to groups of 50 male and female rats for 104 weeks. Ten additional animals per dose group were evaluated at 6 and 15 months. Body Weight, Survival, and Clinical Findings in the 2-Year Studies: Body weights of exposed male and female rats given 1,000 and 10,000 ppm were within 5% of controls throughout the studies. Reduced body weight gain in male and female rats receiving 40,000 ppm was observed by week 15 and the final mean body weights were 87% of controls at week 104. Survival and feed consumption were similar among exposed and control groups throughout the studies. The average amounts of quercetin consumed per day by the 1,000, 10,000 and 40,000 ppm dose groups after week 52 were 40, 400, and 1,900 mg/kg of body weight. Nonneoplastic and Neoplastic Effects in the 2-Year Studies: In male rats, the principal toxic effects associated with the dietary administration of quercetin for 2 years were observed in the kidney. There were dose

  13. The UV-vis absorption spectrum of the flavonol quercetin in methanolic solution: A theoretical investigation

    NASA Astrophysics Data System (ADS)

    Andrade-Filho, T.; Ribeiro, T. C. S.; Del Nero, J.

    2009-07-01

    The UV-vis absorption spectrum of the solvated quercetin molecule in methanol was investigated theoretically by means of an elegant type of QM/MM scheme better known as sequential Monte Carlo/quantum mechanics (S-MC/QM) methodology. A set of 125 uncorrelated Monte Carlo molecular liquid structures were properly selected through the autocorrelation function of the energy in order to be used in the quantum mechanical calculations. These molecular liquid structures were obtained by means of the radial and minimum distance distribution functions. A detailed account of the pattern of hydrogen bond structures obtained in this study is also available. The computed results obtained here were directly compared with the available experimental data in order to validate our theoretical model and through this comparison a very good conformity between theoretical and available experimental results was found.

  14. Formulation, characterization, and evaluation of ligand-conjugated biodegradable quercetin nanoparticles for active targeting.

    PubMed

    Gupta, Anshita; Kaur, Chanchal Deep; Saraf, Shailendra; Saraf, Swarnlata

    2016-05-01

    The aim of this study was to design a targeted drug delivery system carrying a natural anticancer drug Quercetin (Qu), specifically for skin cancer. A central composite design was applied separately for each ligand, and the quadratic model was used for the process. The surface morphology was confirmed by transmission electron microscopy (TEM) and Fourier transform infrared spectroscopy (FTIR), and in vitro release studies were also performed. The MTT assay was performed against two different cell lines, to measure their anticancer potentials and their targeting ability. The study thus reveals that MA-Qu-PLGA and FA-Qu-PLGA nanoparticles (NPs) can be used as effective drug delivery systems for skin cancer treatment encompassing natural drugs. PMID:25813566

  15. Characterization and Antioxidant Activity of Quercetin/Methyl-β-Cyclodextrin Complexes.

    PubMed

    Güleç, Kadri; Demirel, Müzeyyen

    2016-01-01

    Quercetin (Qu), a polyphenolic flavonoid, is one of the most effective plant originated antioxidants. Despite the potential use of Qu in clinical trials, low water solubility, stability problems and the scarcity of cellular bioavailability limit its applications. The purpose of this study was to enhance aqueous solubility, dissolution rate and antioxidant activity of Qu by complexation with Methyl-β- cyclodextrin (M-β-CD). Analyses results showed that the aqueous solubility, dissolution rate and antioxidant activity of the complex were increased 254-fold, ~3-fold and 10% respectively compared to the pure Qu. Complexes were prepared by freeze-drying and evaporation method. The characteristics of the complexes were evaluated by DSC, XRD, (1)H-NMR, FT-IR, SEM, encapsulation efficacy, in-vitro dissolution rate analyses. Antioxidant activity studies on complexes carried out with DPPH tests. Analyses results showed that the formation of the complexes resulted in enhanced solubility with increased its antioxidant activity of Qu. PMID:26521654

  16. Quercetin: a potential natural drug for adjuvant treatment of rheumatoid arthritis.

    PubMed

    Ji, Jian-Jun; Lin, Yuan; Huang, Shan-Shan; Zhang, Hou-Li; Diao, Yun-Peng; Li, Kun

    2013-01-01

    Rheumatoid arthritis (RA) is the rheumatism mainly manifested as disabling joint disease and mainly involves hands, wrists, feet and other small joints. Recurrent arthritis attacks, synovial cell hypertrophy and hyperplasia and bone and cartilage damages eventually lead to joint dysfunction and other complications, and there is no cure. Quercetin (QU) is a kind of natural flavonoids, with lipid-lowering, anti-inflammatory and other pharmacological activities, and minor toxic side effects. Thus, we assume that QU may be an adjuvant natural drug for treatment of RA. The possible mechanism is through regulation of NF-κB, to inhibit the transcription of joint synovitis factors, hinder the generation of inflammatory factors, and inhibit the inflammatory reaction; through inhibiting the activities of VEGF, bFGF, MMP-2 and other cytokines, to inhibit angiogenesis in multiple links and inhibit synovial pannus formation. QU may be an adjuvant natural drug for treatment of RA. PMID:24146468

  17. Preparation and evaluation of folate-modified lipid nanocapsules for quercetin delivery.

    PubMed

    Ding, Buyun; Chen, Ping; Kong, Yan; Zhai, Yingjie; Pang, Xin; Dou, Jinfeng; Zhai, Guangxi

    2014-01-01

    Folate-modified lipid nanocapsule encapsulated quercetin (QT-FALNC) was prepared with phase inversion method. The formulation was optimized by simplex lattice design with encapsulation efficiency and drug loading as index. The encapsulation efficiency and drug loading of the optimal formulation were 96.01% and 2.98%, respectively. The drug concentration in QT-FALNC suspension was 4.29 mg/mL. Under transmission electron microscopy, the QT-FALNC showed spherical shape with a narrow size distribution. The particle size and zeta potential of QT-FALNC were 36.2 nm and -4.76 mV, respectively. The pharmacokinetics study in rats showed that the mean retention time (MRT0-∞) of the non-targeting lipid nanocapsules (LNC) loading quercetin (QT-LNC) and the targeting QT-FALNC was 12.981 h and 15.086 h, respectively, indicating that LNC could prolong the effect of QT in vivo. The in vitro anti-proliferative activity and cellar uptake of QT-FALNC were studied on Hela and MCF-7/MDR cells. The results showed that both QT-LNC and QT-FALNC displayed a stronger cell-killing effect than free QT. The in vivo anti-tumor study indicated that both QT-LNC and QT-FALNC showed the significant inhibition effect on tumor growth in H22 tumor-bearing mice compared with the control. It can be concluded that lipid nanocapsule is a potential carrier for improving solubility and biological activity of QT. PMID:24099639

  18. Quercetin glycosides and chlorogenic acid in highbush blueberry leaf decoction prevent cataractogenesis in vivo and in vitro: Investigation of the effect on calpains, antioxidant and metal chelating properties.

    PubMed

    Ferlemi, Anastasia-Varvara; Makri, Olga E; Mermigki, Penelope G; Lamari, Fotini N; Georgakopoulos, Constantinos D

    2016-04-01

    The present study investigates whether highbush blueberry leaf polyphenols prevent cataractogenesis and the underlying mechanisms. Chlorogenic acid, quercetin, rutin, isoquercetin and hyperoside were quantified in Vaccinium corymbosum leaf decoction (BBL) using HPLC-DAD. Wistar rats were injected subcutaneously with 20 μmol selenite (Na2SeO3)/kg body weight on postnatal (PN) day 10 (Se, n = 8-10/group) only or also intraperitoneally with 100 mg dry BBL/kg body weight on PN days 11 and 12 (SeBBL group, n = 10). Control group received only normal saline (C). Cataract evaluation revealed that BBL significantly prevented lens opacification. It, also, protected lens from selenite oxidative attack and prevented calpain activation, as well as protein loss and aggregation. In vitro studies showed that quercetin attenuated porcine lens turbidity caused by [Formula: see text] or Ca(2+) and interacted efficiently with those ions according to UV-Vis titration experiments. Finally, rutin, isoquercetin and hyperoside moderately inhibited pure human μ-calpain. Conclusively, blueberry leaf extract, a rich source of bioactive polyphenols, prevents cataractogenesis by their strong antioxidant, chelating properties and through direct/indirect inhibition of lens calpains. PMID:26808488

  19. Absorption and excretion of conjugated flavonols, including quercetin-4'-O-beta-glucoside and isorhamnetin-4'-O-beta-glucoside by human volunteers after the consumption of onions.

    PubMed

    Aziz, A A; Edwards, C A; Lean, M E; Crozier, A

    1998-09-01

    Flavonols are polyphenols found ubiquitously in plants and plant-products. Flavonols, particularly quercetin, are potent antioxidants in vitro and their intake has been associated inversely with the incidence of coronary heart disease. The aim of this study was to investigate the accumulation in plasma and excretion in urine of flavonol glucosides following ingestion of lightly fried onions. Five healthy volunteers followed a low-flavonoid diet for 3 days. On day 4, after an overnight fast, subjects were given 300 g of lightly fried yellow onions which contain conjugates of quercetin and isorhamnetin, including quercetin-3,4 '-diO-beta-glucoside, isorhamnetin-4'-O-beta-glucoside and quercetin-4'-O-beta-glucoside. Blood collection was carried out at 0 min, 0.5, 1.0, 1.5, 2, 3, 4, 5 and 24h after the supplement. In addition, subjects collected all their urine for 24h following the onion supplement. Isorhamnetin-4'-O-beta-glucoside and quercetin-4 '-O-beta-glucoside accumulated in plasma with maximum levels, defined as proportion of intake, of 10.7+/-2.6% and 0.13+/-0.03% respectively. The time of the quercetin-4'glucoside peak plasma concentration was 1.3+/-0.2 h after the ingestion of onions while a value of 1.8+/-0.7 h was obtained for isorhamnetin-4'-glucoside. Excretion in urine, as a proportion of intake, was 17.4+/-8.3% for isorhamnetin-4'-O-beta-glucoside and 0.2+/-0.1% for quercetin-4'-O-beta-glucoside. Possible reasons for the accumulation and excretion of isorhamnetin-4'-glucoside in proportionally much higher amounts than quercetin-4'-glucoside are discussed. It is concluded that flavonols are absorbed into the bloodstream as glucosides and minor structural differences affect markedly both the level of accumulation and the extent to which the conjugates are excreted. PMID:9802557

  20. 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

  1. Quantification of Quercetin and Rutin from Benincasa hispida Seeds and Carissa Congesta Roots by High-performance Thin Layer Chromatography and High-performance Liquid Chromatography

    PubMed Central

    Doshi, Gaurav Mahesh; Une, Hemant Devidas

    2016-01-01

    Objective: In Indian Ayurvedic system, Benincasa hispida (BH) and Carissa congesta (CC) are well-known plants used for major and minor ailments. BH has been regarded as Kushmanda, whereas CC has been used in immune-related disorders of the human system. Quercetin and rutin identified from the vast plethora of plant extracts have proved to possess ethnopharmacological relevance. Materials and Methods: In present studies, we have determined quercetin and rutin in terms of percentage in BH seeds and CC roots by high-performance thin layer chromatography (HPTLC) and high-performance liquid chromatography (HPLC). After extraction and phytochemical screening, the extracts were subjected to quantification for the presence of quercetin and rutin by HPTLC and HPLC. Results: HPTLC showed quercetin as 44.60, 27.13% and rutin as 32.00, 36.31% w/w, whereas HPLC revealed quercetin as 34.00, 35.00% and rutin as 21.99, 45.03% w/v in BH and CC extracts, respectively. Conclusion: The BH and CC extracts have elucidated peaks that were corresponding with standard peaks on undertaking chromatographic studies. SUMMARY Quercetin and rutin are isolated from BH seeds and CC roots by High Performance. Thin Layer Chromatography and High Performance Liquid Chromatography. HPTLC revealed presence of quercetin as 44.60, 27.13 % and rutin as 32.00, 36.31 % w/w. HPLC revealed presence of quercetin as 34.00, 35.00 % and rutin as 21.99, 45.03 % w/v. Abbreviation Used: HPTLC: High Performance Thin Layer Chromatography; HPLC: High Pressure Liquid Chromatography, UV: Ultraviolet, CC: Carissa congesta, BH: Benincasa hispida PMID:26941534

  2. Sol-gel synthesis and characterization of SiO2/PEG hybrid materials containing quercetin as implants with antioxidant properties

    NASA Astrophysics Data System (ADS)

    Catauro, Michelina; Bollino, Flavia; Gloria, Antonio

    2016-05-01

    In the present work, Silica/Polyethylene glycol (PEG) hybrid nanocomposites containing an antioxidant agent, the quercetin, were synthesized via sol-gel to be used as implants with antioxidant properties. Fourier transform infrared (FT-IR) analysis proved that a modification of both polymer and quercetin occurs due to synthesis process. Scanning electron microscope (SEM) showed that the proposed materials were hybrid nanocomposites. The bioactivity was ascertained by soaking the samples in a simulated body fluid (SBF).

  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. 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

  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. Protection by the flavonoids quercetin and luteolin against peroxide- or menadione-induced oxidative stress in MC3T3-E1 osteoblast cells.

    PubMed

    Fatokun, Amos A; Tome, Mercedes; Smith, Robert A; Darlington, L Gail; Stone, Trevor W

    2015-01-01

    Potential protective effects of the flavonoids quercetin and luteolin have been examined against the oxidative stress of MC3T3-E1 osteoblast-like cells. Although hydrogen peroxide and menadione reduced cell viability, the toxicity was prevented by desferrioxamine or catalase but not superoxide dismutase, suggesting the involvement of hydrogen peroxide in both cases. Quercetin and luteolin reduced the oxidative damage, especially that caused by hydrogen peroxide. When cultures were pre-incubated with quercetin or luteolin, protection was reduced or lost. Protection was also reduced when a 24 h pre-incubation with the flavonoids was followed by exposure to menadione alone. Pretreating cultures with luteolin impaired protection by quercetin, whereas quercetin pretreatment did not affect protection by luteolin. It is concluded that quercetin and luteolin suppress oxidative damage to MC3T3-E1 cells, especially caused by peroxide. The reduction in protection by pretreatment implies a down-regulation of part of the toxic transduction pathway. PMID:25427161

  7. Combinatorial selection of molecular conformations and supramolecular synthons in quercetin cocrystal landscapes: a route to ternary solids

    PubMed Central

    Dubey, Ritesh; Desiraju, Gautam R.

    2015-01-01

    The crystallization of 28 binary and ternary cocrystals of quercetin with dibasic coformers is analyzed in terms of a combinatorial selection from a solution of preferred molecular conformations and supramolecular synthons. The crystal structures are characterized by distinctive O—H⋯N and O—H⋯O based synthons and are classified as nonporous, porous and helical. Variability in molecular conformation and synthon structure led to an increase in the energetic and structural space around the crystallization event. This space is the crystal structure landscape of the compound and is explored by fine-tuning the experimental conditions of crystallization. In the landscape context, we develop a strategy for the isolation of ternary cocrystals with the use of auxiliary template molecules to reduce the molecular and supramolecular ‘confusion’ that is inherent in a molecule like quercetin. The absence of concomitant polymorphism in this study highlights the selectivity in conformation and synthon choice from the virtual combinatorial library in solution. PMID:26175900

  8. Skin penetration of epigallocatechin-3-gallate and quercetin from green tea and Ginkgo biloba extracts vehiculated in cosmetic formulations.

    PubMed

    dal Belo, S E; Gaspar, L R; Maia Campos, P M B G; Marty, J-P

    2009-01-01

    Green tea (Camellia sinensis) and Ginkgo biloba extracts in cosmetic formulations have been suggested to protect the skin against UV-induced damage and skin ageing. Thus, it is very important to assess the human skin penetration of their major flavonoids to verify if they penetrate and remain in the skin to exert their proposed effects. The aim of this study was to evaluate the human skin penetration of epigallocatechin-3-gallate (EGCG) and quercetin from green tea and G. biloba extracts vehiculated in cosmetic formulations. This study was conducted with fresh dermatomed human Caucasian skin from abdominal surgery mounted on static Franz diffusion cells. Skin samples were mounted between two diffusion half-cells and 10 mg/cm(2) of formulations supplemented with 6% of green tea or G. biloba extract were applied on the skin surface. The receptor fluid was removed after 6 and 24 h and analyzed by high-performance liquid chromatography for the quantification of the flavonoids. The stratum corneum was removed by tape stripping and immersed in methanol and the epidermis was mechanically separated from the dermis and triturated in methanol to extract EGCG and quercetin. The results showed that the flavonoids under study penetrated into the skin, without reaching the receptor fluid. The majority of EGCG was quantified in the stratum corneum (0.87 microg/cm(2)), which was statistically higher than the EGCG concentrations found in viable epidermis (0.54 microg/cm(2)) and in the dermis (0.38 microg/cm(2)). The majority of quercetin was quantified in the viable epidermis (0.23 microg/cm(2)), which was statistically higher than the EGCG concentration found in the stratum corneum layer (0.17 microg/cm(2)). Finally, it can be concluded that EGCG and quercetin from green tea and G. biloba extracts vehiculated in cosmetic formulations presented good skin penetration and retention, which can favor their skin effects. PMID:19786823

  9. PI-103 and Quercetin Attenuate PI3K-AKT Signaling Pathway in T- Cell Lymphoma Exposed to Hydrogen Peroxide

    PubMed Central

    Maurya, Akhilendra Kumar; Vinayak, Manjula

    2016-01-01

    Phosphatidylinositol 3 kinase—protein kinase B (PI3K-AKT) pathway has been considered as major drug target site due to its frequent activation in cancer. AKT regulates the activity of various targets to promote tumorigenesis and metastasis. Accumulation of reactive oxygen species (ROS) has been linked to oxidative stress and regulation of signaling pathways for metabolic adaptation of tumor microenvironment. Hydrogen peroxide (H2O2) in this context is used as ROS source for oxidative stress preconditioning. Antioxidants are commonly considered to be beneficial to reduce detrimental effects of ROS and are recommended as dietary supplements. Quercetin, a ubiquitous bioactive flavonoid is a dietary component which has attracted much of interest due to its potential health-promoting effects. Present study is aimed to analyze PI3K-AKT signaling pathway in H2O2 exposed Dalton’s lymphoma ascite (DLA) cells. Further, regulation of PI3K-AKT pathway by quercetin as well as PI-103, an inhibitor of PI3K was analyzed. Exposure of H2O2 (1mM H2O2 for 30min) to DLA cells caused ROS accumulation and resulted in increased phosphorylation of PI3K and downstream proteins PDK1 and AKT (Ser-473 and Thr-308), cell survival factors BAD and ERK1/2, as well as TNFR1. However, level of tumor suppressor PTEN was declined. Both PI-103 & quercetin suppressed the enhanced level of ROS and significantly down-regulated phosphorylation of AKT, PDK1, BAD and level of TNFR1 as well as increased the level of PTEN in H2O2 induced lymphoma cells. The overall result suggests that quercetin and PI3K inhibitor PI-103 attenuate PI3K-AKT pathway in a similar mechanism. PMID:27494022

  10. Comparison of membrane-protective activity of antioxidants quercetine and Gratiola Officinalis L. extract under conditions of photodynamic haemolysis

    NASA Astrophysics Data System (ADS)

    Tkachenko, N. V.; Bykova, E. V.; Pravdin, A. B.; Navolokin, N. A.; Polukonova, N. V.; Bucharskaya, A. B.; Mudrak, D. A.; Prilepskii, A. Y.

    2016-04-01

    In the present work the effectiveness of antioxidants quercetine (a pure chemical) and Gratiola officinalis extract, which is obtained by a new method of extraction from plant material, is investigated on the model of photodynamic haemolysis that is a rather convenient method to monitor the rate of cell membranes oxidative destruction. The effect of these antioxidants on the rate of photodynamic haemolysis is considered as a measure of membranoprotective efficiency.

  11. Quercetin encapsulation in modified silica nanoparticles: potential use against Cu(II)-induced oxidative stress in neurodegeneration.

    PubMed

    Nday, Christiane M; Halevas, Eleftherios; Jackson, Graham E; Salifoglou, Athanasios

    2015-04-01

    Neurodegenerative diseases entail deeply complex processes, intimately associated with progressive brain damage reflecting cellular demise. Biochemical reactivity linked to such processes in Alzheimer's disease involves, among others, metal-induced oxidative stress contributing to neuronal cell death. Prominent among redox active metals inducing oxidative stress is Cu(II). Poised to develop molecular technology counteracting oxidative stress, efforts were launched to prepare bioactive hybrid nanoparticles, capable of working as host-carriers of potent antioxidants, such as the natural flavonoid quercetin. Employing synthetic protocols consistent with the assembly of silica nanoparticles, PEGylated and CTAB-modified materials were synthesized. Subsequent concentration-dependent loading of quercetin led to well-defined molecular carriers, the antioxidant efficiency of which was determined through drug release studies using UV-visible spectroscopy. The physicochemical characterization (elemental analysis, particle size, z-potential, FT-IR, thermogravimetric analysis, scanning electron microscopy) of the empty and loaded silica nanoparticles led to the formulation of optimized material linked to the delivery of the encapsulated antioxidant to primary rat hippocampal cultures under oxidative stress. Entrapment and drug release studies showed a) the competence of hybrid nanoparticles as far as the loading capacity in quercetin (concentration dependence), b) congruence with the physicochemical features determined, and c) the release profile of the nanoparticle load under oxidative stress in neuronal cultures. The bio-activity profile of quercetin nanoparticles in a neurodegenerative environment brought on by Cu(II) a) denotes the improved specificity of antioxidant reactivity counteracting oxidative stress, and b) sets the stage for the development of molecular protection and preventive medical nanotechnology of relevance to neurodegenerative Alzheimer's disease. PMID

  12. Cr(III)/Cr(VI) speciation determination of chromium in water samples by luminescence quenching of quercetin.

    PubMed

    Hosseini, Mohammad Saeid; Belador, Foroogh

    2009-06-15

    A highly sensitive and selective method has been proposed for direct speciation determination of trace amounts of chromium in water samples using quercetin. The method is based on mixing 5 mL of diluted quercetin solution dissolved in n-amyl alcohol with 5 mL of acidic solution (pH 1) of Cr(VI), which is accomplished with luminescence quenching of the organic phase due to partially oxidation of quercetin content. Cr(VI) is determined by measuring the diminished content of quercetin with spectrofluorometric method (lambda(ex)=276 nm, lambda(em)=331 nm). After oxidation of the Cr(III) content to Cr(VI) and determination of the total chromium as Cr(VI), the Cr(III) is obtained by subtracting. All the variables were studied in order to optimize the reaction conditions. No considerable interference was observed due to the presence of co-existing anions and cations. The calibration graphs were linear in the range 1.0 x 10(-7) to 2.0 x 10(-6)M with the detection limits of 9.1 x 10(-9)M. The R.S.D. obtained for 1.0 x 10(-6)M of Cr(VI) was 1.7% (n=7). Validation of the measurements was confirmed using standard reference materials. The method was applied to determine the chromium species in natural water samples. The recoveries obtained for the spiked amount of chromium species were >98%, which denote on satisfactorily application of the method. PMID:19135303

  13. Computational screen and experimental validation of anti-influenza effects of quercetin and chlorogenic acid from traditional Chinese medicine

    PubMed Central

    Liu, Zekun; Zhao, Junpeng; Li, Weichen; Shen, Li; Huang, Shengbo; Tang, Jingjing; Duan, Jie; Fang, Fang; Huang, Yuelong; Chang, Haiyan; Chen, Ze; Zhang, Ran

    2016-01-01

    The Influenza A virus is a great threat for human health, while various subtypes of the virus made it difficult to develop drugs. With the development of state-of-art computational chemistry, computational molecular docking could serve as a virtual screen of potential leading compound. In this study, we performed molecular docking for influenza A H1N1 (A/PR/8/34) with small molecules such as quercetin and chlorogenic acid, which were derived from traditional Chinese medicine. The results showed that these small molecules have strong binding abilities with neuraminidase from H1N1 (A/PR/8/34). Further details showed that the structural features of the molecules might be helpful for further drug design and development. The experiments in vitro, in vivo have validated the anti-influenza effect of quercetin and chlorogenic acid, which indicating comparable protection effects as zanamivir. Taken together, it was proposed that chlorogenic acid and quercetin could be employed as the effective lead compounds for anti-influenza A H1N1. PMID:26754609

  14. Effect of pioglitazone, quercetin and hydroxy citric acid on extracellular matrix components in experimentally induced non-alcoholic steatohepatitis

    PubMed Central

    Mohan, Surapaneni Krishna; Veeraraghavan, Vishnu Priya; Jainu, Mallika

    2015-01-01

    Objective(s): Non-alcoholic steatohepatitis (NASH), is an important component of Non-alcoholic fatty liver disease (NAFLD) spectrum, which progresses to the end stage liver disease, if not diagnosed and treated properly. The disproportionate production of pro- and anti-inflammatory adipokines secreted from fat contributes to the pathogenesis of NASH. In this study, the comparative effect of pioglitazone, quercetin and hydroxy citric acid on extracellular matrix (ECM) component levels were studied in experimentally induced NASH. Materials and Methods: The experimental protocol consists of using 48 male Wister rats, which were divided into 8 groups. The levels of hyaluronic acid, leptin and adiponectin were monitored in experimental NASH. Results: The experimental NASH rats treated with pioglitazone showed significant decrease in the levels of hyaluronic acid and significant increase in adiponectin levels when compared to experimentally induced NASH group, but did not show any effect on the levels of leptin. Contrary to these two drugs, viz. pioglitazone and hydroxy citric acid, the group treated with quercetin showed significant decrease in the levels of hyaluronic acid and leptin and significant decrease in adiponectin levels compared with that of experimentally induced NASH NASH group, offering maximum protection against NASH. Conclusion: Considering our findings, it could be concluded that quercetin may offer maximum protection against NASH by significantly increasing the levels of adiponectin, when compared to pioglitazone and hydroxy citric acid. PMID:26557974

  15. Microchannel emulsification study on formulation and stability characterization of monodisperse oil-in-water emulsions encapsulating quercetin.

    PubMed

    Khalid, Nauman; Kobayashi, Isao; Neves, Marcos A; Uemura, Kunihiko; Nakajima, Mitsutoshi; Nabetani, Hiroshi

    2016-12-01

    The study used microchannel emulsification (MCE) to encapsulate quercetin in food grade oil-in-water (O/W) emulsions. A silicon microchannel plate (Model WMS 1-2) comprised of 10,300 discrete 10×104μm microslots was connected to a circular microhole with an inner diameter of 10μm. 1% (w/w) Tween 20 was used as optimized emulsifier in Milli-Q water, while 0.4mgml(-1) quercetin in different oils served as a dispersed phase. The MCE was carried by injecting the dispersed phase at 2mlh(-1). Successful emulsification was conducted below the critical dispersed phase flux, with a Sauter mean diameter of 29μm and relative span factor below 0.25. The O/W emulsions remained stable in terms of droplet coalescence at 4 and 25°C for 30days. The encapsulation efficiency of quercetin in the O/W emulsions was 80% at 4°C and 70% at 25°C during the evaluated storage period. PMID:27374502

  16. Computational screen and experimental validation of anti-influenza effects of quercetin and chlorogenic acid from traditional Chinese medicine.

    PubMed

    Liu, Zekun; Zhao, Junpeng; Li, Weichen; Shen, Li; Huang, Shengbo; Tang, Jingjing; Duan, Jie; Fang, Fang; Huang, Yuelong; Chang, Haiyan; Chen, Ze; Zhang, Ran

    2016-01-01

    The Influenza A virus is a great threat for human health, while various subtypes of the virus made it difficult to develop drugs. With the development of state-of-art computational chemistry, computational molecular docking could serve as a virtual screen of potential leading compound. In this study, we performed molecular docking for influenza A H1N1 (A/PR/8/34) with small molecules such as quercetin and chlorogenic acid, which were derived from traditional Chinese medicine. The results showed that these small molecules have strong binding abilities with neuraminidase from H1N1 (A/PR/8/34). Further details showed that the structural features of the molecules might be helpful for further drug design and development. The experiments in vitro, in vivo have validated the anti-influenza effect of quercetin and chlorogenic acid, which indicating comparable protection effects as zanamivir. Taken together, it was proposed that chlorogenic acid and quercetin could be employed as the effective lead compounds for anti-influenza A H1N1. PMID:26754609

  17. Quercetin-loaded freeze-dried nanomicelles: Improving absorption and anti-glioma efficiency in vitro and in vivo.

    PubMed

    Wang, Gang; Wang, Jun-Jie; Chen, Xuan-Li; Du, Li; Li, Fei

    2016-08-10

    To improve its poor aqueous solubility and stability, the potential chemopreventive agent quercetin was encapsulated in freeze-dried polymeric micelles by a thin film hydration and vacuum freeze-drying process before being used for glioma chemotherapy. The micelle characteristics, release profile, cellular uptake, intracellular drug concentration, transport across the blood-brain barrier, and antitumor efficiency in vivo were investigated. Results showed that the particle size of quercetin-loaded freeze-dried nanomicelles (QUE-FD-NMs) ranged from 20 to 80nm, with an efficiently sustained release profile. Increased intracellular uptake into Caco-2 cells with low cytotoxicity, efficient penetration of BBB, and powerful cytotoxicity on C6 glioma cells were observed. QUE-FD-NMs accumulated in tumor-bearing brain tissues and exhibited significant antitumor effects in vivo, which significantly benefited the survival of glioma-bearing mice. These findings suggest that freeze-drying micelles loaded with quercetin is a promising drug delivery method for glioma therapy. PMID:27242199

  18. Quercetin and gallic acid mediated synthesis of bimetallic (silver and selenium) nanoparticles and their antitumor and antimicrobial potential.

    PubMed

    Mittal, Amit Kumar; Kumar, Sanjay; Banerjee, Uttam Chand

    2014-10-01

    In this study a synthetic approach for the stable, mono-dispersed high yielding bimetallic (Ag-Se) nanoparticles by quercetin and gallic acid is described. The bimetallic nanoparticles were synthesized at room temperature. Different reaction parameters (concentration of quercetin, gallic acid and Ag/Se salt, pH, temperature and reaction time) were optimized to control the properties of nanoparticles. The nanoparticles were characterized by various analytical techniques and their size was determined to be 30-35 nm. Our findings suggest that both the reduction as well as stabilization of nanoparticles were achieved by the flavonoids and phenolics. This study describes the efficacy of quercetin and gallic acid mediated synthesis of bimetallic (Ag-Se) nanoparticles and their in vitro antioxidant, antimicrobial (Gram-positive and Gram-negative bacteria) and antitumor potentials. The synthesized Ag-Se nanoparticles were used as anticancer agents for Dalton lymphoma (DL) cells and in in vitro 80% of its viability was reduced at 50 μg/mL. PMID:25000181

  19. Dimerization of quercetin, Diels-Alder vs. radical-coupling approach: a joint thermodynamics, kinetics, and topological study.

    PubMed

    Fourré, Isabelle; Di Meo, Florent; Podloucká, Pavlína; Otyepka, Michal; Trouillas, Patrick

    2016-08-01

    Quercetin is a prototypical antioxidant and prominent member of flavonoids, a large group of natural polyphenols. The oxidation of quercetin may lead to its dimerization, which is a paradigm of the more general polyphenol oligomerization. There exist two opposing mechanisms to describe the dimerization process, namely radical-coupling or Diels-Alder reactions. This work presents a comprehensive rationalization of this dimerization process, acquired from density functional theory (DFT) calculations. It is found that the two-step radical-coupling pathway is thermodynamically and kinetically preferred over the Diels-Alder reaction. This is in agreement with the experimental results showing the formation of only one isomer, whereas the Diels-Alder mechanism would yield two isomers. The evolution in bonding, occurring during these two processes, is investigated using the atoms in molecules (AIM) and electron localization function (ELF) topological approaches. It is shown that some electron density is accumulated between the fragments in the transition state of the radical-coupling reaction, but not in the transition state of the Diels-Alder process. Graphical Abstract Quantum chemistry calculations of the dimerization process of quercetin show that a radical coupling approach is preferred to a Diels-Alder type reaction, in agreement with experimental results. Analysis of the bonding evolution highlights the reaction mechanism. PMID:27449669

  20. An on-line method for pressurized hot water extraction and enzymatic hydrolysis of quercetin glucosides from onions.

    PubMed

    Lindahl, Sofia; Liu, Jiayin; Khan, Samiullah; Karlsson, Eva Nordberg; Turner, Charlotta

    2013-06-27

    A novel environmentally sound continuous-flow hot water extraction and enzymatic hydrolysis method for determination of quercetin in onion raw materials was successfully constructed using a stepwise optimization approach. In the first step, enzymatic hydrolysis of quercetin-3,4'-diglucoside to quercetin was optimized using a three level central composite design considering temperature (75-95°C), pH (3-6) and volume concentration of ethanol (5-15%). The enzyme used was a thermostable β-glucosidase variant (termed TnBgl1A_N221S/P342L) covalently immobilized on either of two acrylic support-materials (Eupergit(®) C 250L or monolithic cryogel). Optimal reaction conditions were irrespective of support 84°C, 5% ethanol and pH 5.5, and at these conditions, no significant loss of enzyme activity was observed during 72 h of use. In a second step, hot water extractions from chopped yellow onions, run at the optimal temperature for hydrolysis, were optimized in a two level design with respect to pH (2.6 and 5.5), ethanol concentration (0 and 5%) and flow rate (1 and 3 mL min(-1)) Obtained results showed that the total quercetin extraction yield was 1.7 times higher using a flow rate of 3 mL min(-1) (extraction time 90 min), compared to a flow rate of 1 mL min(-1) (extraction time 240 min). Presence of 5% ethanol was favorable for the extraction yield, while a further decrease in pH was not, not even for the extraction step alone. Finally, the complete continuous flow method (84°C, 5% ethanol, pH 5.5, 3 mL min(-1)) was used to extract quercetin from yellow, red and shallot onions and resulted in higher or similar yield (e.g. 8.4±0.7 μmol g(-1) fresh weight yellow onion) compared to a conventional batch extraction method using methanol as extraction solvent. PMID:23764443

  1. Preventive effect of the flavonoid, quercetin, on hepatic cancer in rats via oxidant/antioxidant activity: molecular and histological evidences

    PubMed Central

    Seufi, AlaaEddeen M; Ibrahim, Safinz S; Elmaghraby, Tarek K; Hafez, Elsayed E

    2009-01-01

    Background The incidence of hepatocellular carcinoma is increasing in many countries. The estimated number of new cases annually is over 500,000, and the yearly incidence comprises between 2.5 and 7% of patients with liver cirrhosis. The incidence varies between different geographic areas, being higher in developing areas; males are predominantly affected, with a 2:3 male/female ratio Methods Experiments were designed to examine the effect of N-Nitrosodiethylamine (NDEA) as cancer-inducer compound and to confirm the preventive effect of the flavonoid quercetin on hepatocellular carcinoma in rats. Briefly, thirty six male albino rats of Wistar strain were divided into 3 groups: the 1st group was administered NDEA alone (NDEA-treated), the 2nd group was treated simultaneously with NDEA and quercetin (NDEA+Q) and the 3rd group was used as control (CON). Randomly amplified polymorphic DNA polymerase chain reaction (RAPD-PCR) as well as p53-specifi PCR assays were employed to determine genomic difference between treated, and control animals. Histological confirmation as well as oxidant/antioxidant status of the liver tissue was done. Results RAPD analysis of liver samples generated 8 monomorphic bands and 22 polymorphic bands in a total of 30-banded RAPD patterns. Cluster analysis and statistical analyses of RAPD data resulted in grouping control and NDEA+Q samples in the same group with 80% similarity cut-off value. NDEA-treated samples were clustered in a separate group. Specific PCR assay for polymorphism of P53 gene revealed a uniform pattern of allele separation in both control and NDEA+Q samples. Quercetin anticancer effect was exhibited in significant decrease of oxidative stress and significant decrease of antioxidant activity. Histopathological studies showed normal liver histology of the NDEA+Q samples. Meanwhile, several cancer-induced features were clearly observable in NDEA-treated samples. Conclusion This paper demonstrated that preventive effect of

  2. Olive leaf extracts protect cardiomyocytes against 4-hydroxynonenal-induced toxicity in vitro: comparison with oleuropein, hydroxytyrosol, and quercetin.

    PubMed

    Bali, Elif Burcu; Ergin, Volkan; Rackova, Lucia; Bayraktar, Oğuz; Küçükboyaci, Nurgün; Karasu, Çimen

    2014-08-01

    Olive (Olea europaea) leaf, an important traditional herbal medicine, displays cardioprotection that may be related to the cellular redox modulating effects of its polyphenolic constituents. This study was undertaken to investigate the protective effect of the ethanolic and methanolic extracts of olive leaves compared to the effects of oleuropein, hydroxytyrosol, and quercetin as a positive standard in a carbonyl compound (4-hydroxynonenal)-induced model of oxidative damage to rat cardiomyocytes (H9c2). Cell viability was detected by the MTT assay; reactive oxygen species production was assessed by the 2',7'-dichlorodihydrofluorescein diacetate method, and the mitochondrial membrane potential was determined using a JC-1 dye kit. Phospho-Hsp27 (Ser82), phospho-MAPKAPK-2 (Thr334), phospho-c-Jun (Ser73), cleaved-caspase-3 (cl-CASP3) (Asp175), and phospho-SAPK/JNK (Thr183/Tyr185) were measured by Western blotting. The ethanolic and methanolic extracts of olive leaves inhibited 4-hydroxynonenal-induced apoptosis, characterized by increased reactive oxygen species production, impaired viability (LD50: 25 µM), mitochondrial dysfunction, and activation of pro-apoptotic cl-CASP3. The ethanolic and methanolic extracts of olive leaves also inhibited 4-hydroxynonenal-induced phosphorylation of stress-activated transcription factors, and the effects of extracts on p-SAPK/JNK, p-Hsp27, and p-MAPKAPK-2 were found to be concentration-dependent and comparable with oleuropein, hydroxytyrosol, and quercetin. While the methanolic extract downregulated 4-hydroxynonenal-induced p-MAPKAPK-2 and p-c-Jun more than the ethanolic extract, it exerted a less inhibitory effect than the ethanolic extract on 4-hydroxynonenal-induced p-SAPK/JNK and p-Hsp27. cl-CASP3 and p-Hsp27 were attenuated, especially by quercetin. Experiments showed a predominant reactive oxygen species inhibitory and mitochondrial protecting ability at a concentration of 1-10 µg/mL of each extract, oleuropein

  3. Entrapping quercetin in silica/polyethylene glycol hybrid materials: Chemical characterization and biocompatibility.

    PubMed

    Catauro, Michelina; Bollino, Flavia; Nocera, Paola; Piccolella, Simona; Pacifico, Severina

    2016-11-01

    Sol-gel synthesis was exploited to entrap quercetin, a natural occurring antioxidant polyphenol, in silica-based hybrid materials, which differed in their polyethylene glycol (PEG) content (6, 12, 24 and 50wt%). The materials obtained, whose nano-composite nature was ascertained by Scanning Electron Microscopy (SEM), were chemically characterized by Fourier Transform InfraRed (FT-IR) and UV-Vis spectroscopies. The results prove that a reaction between the polymer and the drug occurred. Bioactivity tests showed their ability to induce hydroxyapatite nucleation on the sample surfaces. The direct contact method was applied to screen the cytotoxicity of the synthetized materials towards fibroblast NIH 3T3 cells, commonly used for in vitro biocompatibility studies, and three nervous system cell lines (neuroblastoma SH-SY5Y, glioma U251, and pheochromocytoma PC12 cell lines), adopted as models in oxidative stress related studies. Using the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay NIH 3T3 proliferation was assessed and the morphology was not compromised by direct exposure to the materials. Analogously, PC-12, and U-251 cell lines were not affected by new materials. SH-SY5Y appeared to be the most sensitive cell line with cytotoxic effects of 20-35%. PMID:27524014

  4. Quercetin conjugated silica particles as novel biofunctional hybrid materials for biological applications.

    PubMed

    Vergara-Castañeda, Hayde; Hernandez-Martinez, Angel R; Estevez, Miriam; Mendoza, Sandra; Luna-Barcenas, Gabriel; Pool, Héctor

    2016-03-15

    The aim of this work is to formulate biofunctional hybrid materials (HMs) with quercetin (QC) and silica particles (SiPs) by simple methods such as sol-gel and QC conjugation. Physicochemical characterization included particle size, zeta potential (ζ), FTIR and SEM imaging. Spherical particles with ca. 115 nm in diameter were produced, ζ and FTIR demonstrated that QC conjugation was successfully achieved. Electrochemical analyses performed by cyclic voltammetry (CV) suggested that potential binding sites between QC and SiPs may be at functional groups from A ring or C ring, affecting the transfer electron of resorcinol moiety. Iron chelating activity and lipid peroxidation assays showed that after conjugation to SiPs, QC decreased its metal chelating activity, but anti-radical properties is maintained. Our results demonstrated that our proposed method is simple and effective to obtain bio-functional HMs. Our findings prove to be useful in the design of protective approaches against lipid oxidation in food, pharmaceutical, and cosmetics fields. PMID:26704475

  5. Development of a quercetin-loaded nanostructured lipid carrier formulation for topical delivery.

    PubMed

    Chen-yu, Guo; Chun-fen, Yang; Qi-lu, Li; Qi, Tan; Yan-wei, Xi; Wei-na, Liu; Guang-xi, Zhai

    2012-07-01

    The main objective of this study was to evaluate the potential of quercetin-loaded nanostructured lipid carriers (QT-NLCs) as a topical delivery system. QT-NLCs were prepared by the method of emulsion evaporation-solidification at low temperature. The average entrapment efficiency and drug loading of the optimized QT-NLCs were 89.95 ± 0.16% and 3.05 ± 0.01%, respectively. Under the transmission electron microscope, the nanoparticles were spherically shaped. The average particle size was 215.2 nm, the zeta potential was -20.10 ± 1.22 mV and pH value of QT-NLCs system was 4.65. Topical delivery of QT in the form of NLCs was investigated in vitro and in vivo. The results showed that QT-NLCs could promote the permeation of QT, increase the amount of QT retention in epidermis and dermis, and enhance the effect of anti-oxidation and anti-inflammation exerted by QT. Then the mechanism of NLCs for facilitating drug penetration was further investigated through histological sections. In conclusion, NLCs could be a promising vehicle for topical delivery of QT. PMID:22486962

  6. Hypocholesterolemic Efficacy of Quercetin Rich Onion Juice in Healthy Mild Hypercholesterolemic Adults: A Pilot Study.

    PubMed

    Lu, Tsong-Ming; Chiu, Hui-Fang; Shen, You-Cheng; Chung, Chia-Chun; Venkatakrishnan, Kamesh; Wang, Chin-Kun

    2015-12-01

    Onion (Allium cepa L.) is widely employed as a food ingredient as well as traditional remedy to treat fever, burns, and scurvy. The present study focused on the modulator efficacy of the quercetin rich onion juice on lipid profile and antioxidant status in mildly hypercholesterolemic subjects. Twenty-four healthy subjects with mild hypercholesterolemia (≧ 200 mg/dL) were recruited and divided into two groups, and they consumed 100 mL of onion juice or placebo every day for 8 weeks. Fasting blood samples were collected at initial, 2nd, 6th, 8th, 10th week for estimating various biochemical assays, as well as anthropometric indices. After 8 weeks of intervention, onion juice greatly decreased (p < 0.05) waist circumference, total cholesterol and LDL-c. In addition, it elevates (p < 0.05) total antioxidation capacity and prolong lag-time of LDL oxidation were also noted. To conclude, drinking onion juice could markedly suppress cholesterol level and elevate total antioxidation capacity. Hence, onion juice was probably recommended for combating various cardiovascular diseases. PMID:26385226

  7. Hyperglycemia and Anthocyanin Inhibit Quercetin Metabolism in HepG2 Cells.

    PubMed

    Hashimoto, Naoto; Blumberg, Jeffrey B; Chen, C-Y Oliver

    2016-02-01

    A high glucose (Glu) milieu promotes generation of reactive oxygen species, which may not only cause cellular damage, but also modulate phase II enzymes that are responsible for the metabolism of flavonoids. Thus, we examined the effect of a high Glu milieu on quercetin (Q) metabolism in HepG2 cells. HepG2 cells were grown for 3 days in Glu ranging from 5.5 to 50 mmol/L and/or cyanidin-3-glucoside (C3G) ranging from 0 to 25 μmol/L. Subsequently, the capacity of HepG2 cells to metabolize Q was assessed for up to 16 h. Q metabolites were analyzed by high-performance liquid chromatography. Four major Q metabolites were observed in the culture medium and inside the HepG2 cells. Three of these metabolites appear to be sulfated forms of Q or methylated Q, and one was a methylated Q. These metabolites and Q itself were reduced or tended to be reduced in cells grown in a high Glu compared to a normal Glu medium. Addition of C3G or superoxide dismutase plus catalase did not prevent or enhance reduction of Q metabolites. In vitro, a hyperglycemic milieu decreases the production of the principal Q metabolites in HepG2 cells, mediated through mechanisms independent of oxidative stress. PMID:26692239

  8. Protective effects of quercetine on the neuronal injury in frontal cortex after chronic toluene exposure.

    PubMed

    Kanter, Mehmet

    2013-08-01

    The aim of this study was designed to evaluate the possible protective effects of quercetine (QE) on the neuronal injury in the frontal cortex after chronic toluene exposure in rats. The rats were randomly allotted into one of the three experimental groups, namely, groups A (control), B (toluene treated) and C (toluene-treated with QE), where each group contains 10 animals. Control group received 1 ml of normal saline solution, and toluene treatment was performed by the inhalation of 3000 ppm toluene in an 8-h/day and 6-day/week order for 12 weeks. The rats in QE-treated group was given QE (15 mg/kg body weight) once a day intraperitoneally for 12 weeks, starting just after toluene exposure. Tissue samples were obtained for histopathological investigation. To date, no histopathological changes of neurodegeneration in the frontal cortex after chronic toluene exposure in rats by QE treatment have been reported. In this study, the morphology of neurons in the QE treatment group was well protected. Chronic toluene exposure caused severe degenerative changes, shrunken cytoplasm and extensively dark picnotic nuclei in neurons of the frontal cortex. We conclude that QE therapy causes morphologic improvement in neurodegeneration of frontal cortex after chronic toluene exposure in rats. We believe that further preclinical research into the utility of QE may indicate its usefulness as a potential treatment on neurodegeneration after chronic toluene exposure in rats. PMID:22252859

  9. Determination of thorium using phenylfluorone and quercetin in the presence of surfactants and protective colloids

    SciTech Connect

    Zaki, M.T.M.; El-Sayed, A.Y.

    1995-06-01

    Two sensitive spectrophotometric methods have been proposed for the determination of thorium with phenylfluorone (PF) and quercetin (Quer) in the presence of cetylpyridinium bromide (CPB) and polyvinylpyrrolidone (PVP), respectively. The optimum conditions for complexation reactions have been thoroughly investigated. The 1:3:4 (Th-PF-CPB) ternary complex and the 1:3 (Th-Quer) binary complex in the presence of PVP, are formed in the pH range 8.0-8.6 and 9.8-10.6, with molar absorptivities of 1.55x10{sup 5} and 6.25x10{sup 4} l mol{sup {minus}1} cm{sup {minus}1}, at 568 and 445 nm, respectively. The methods are rectilinear for 0.10-1.66 and 0.21-4.3 mg Th.1{sup {minus}1} and their detection limits (signal-to-noise ratio = 3) are 0.082 and 0.139 mg.1{sup {minus}1}, respectively. Results of analysis of thorium in monazite samples using these methods were in good agreement with those obtained by X-ray fluorescence spectrometry.

  10. Quercetin/β-cyclodextrin inclusion complex embedded nanofibres: Slow release and high solubility.

    PubMed

    Aytac, Zeynep; Kusku, Semran Ipek; Durgun, Engin; Uyar, Tamer

    2016-04-15

    Electrospinning of polyacrylic acid (PAA) nanofibres (NF) incorporating β-cyclodextrin inclusion complex (β-CD-IC) of quercetin (QU) was performed. Here, β-CD was used as not only the crosslinking agent for PAA nanofibres but also as a host molecule for inclusion of QU. The phase solubility test showed enhanced solubility of QU due to the inclusion complexation; in addition, the stoichiometry of QU/β-CD-IC was determined to be 1:1. Computational modelling studies confirmed that 1:1 and 1:2 complex formation are desirable; 1:1 complex formation was chosen to have higher weight loading of QU. SEM images showed that PAA/QU/β-CD-IC-NF were bead-free and uniform. XRD indicated that PAA/QU/β-CD-IC-NF were amorphous in nature without the crystalline peaks of QU. Comparative results revealed that the release profile of QU from PAA/QU/β-CD-IC-NF was much slower but greater in total than from PAA/QU/β-CD-IC-film. Moreover, high antioxidant activity and photostability of QU was achieved in PAA/QU/β-CD-IC-NF. PMID:26617028

  11. Flavonols (kaempeferol, quercetin, myricetin) contents of selected fruits, vegetables and medicinal plants.

    PubMed

    Sultana, Bushra; Anwar, Farooq

    2008-06-01

    The concentrations of flavonols (kaempeferol, quercetin, myricetin) were determined in 22 plant materials (9 vegetables, 5 fruits, and 8 medicinal plant organs). The materials were extracted with acidified methanol (methanol/HCl, 100:1, v/v) and analyzed by reverse phase high-performance liquid chromatographic (RP-HPLC) with UV detection. The total flavonols contents varied significantly (P<0.05) among vegetables, fruits and medicinal plant organs ranged from 0 to 1720.5, 459.9 to 3575.4, and 2.42 to 6125.6mgkg(-1) of dry matter, respectively. Among vegetables, spinach and cauliflower exhibited the highest amounts of flavonols (1720.5 and 1603.9mgkg(-1), respectively), however, no flavonols were detected in garlic. Within fruits, highest level of flavonols was observed in strawberry (3575.4mgkg(-1)), whereas, the lowest in apple fruit (459.9mgkg(-1)). Of the medicinal plant organs, moringa and aloe vera leaves contained the highest contents of flavonols (6125.6 and 1636.04mgkg(-1)), respectively, whereas, lowest was present in barks (2.42-274.07mgkg(-1)). Overall, leafy green vegetables, soft fruits and medicinal plant leaves exhibited higher levels of flavonols. PMID:26065748

  12. Viscum album L. extract and quercetin reduce cyclophosphamide-induced cardiotoxicity, urotoxicity and genotoxicity in mice.

    PubMed

    Sekeroğlu, Vedat; Aydin, Birsen; Sekeroğlu, Zülal Atli

    2011-01-01

    Possible protective effects of a methanolic extract of Viscum album (VA) and quercetin (QE) against cyclophosphamide (CP) induced cardiotoxicity, urotoxicity and genotoxicity in mice were evaluated. Mice were administered orally VA (250 mg/kg/day) and QE (50 mg/kg/day) for 10 days alone or in combination with CP. After the same doses of VA and QE given for 7 days, rats were intraperitoneally administered CP (40 mg/kg) on days 8 and 9 of the experiment. Cardiotoxic, urotoxic and genotoxic effects were examined in serum, heart, bladder and bone marrow. Significant decreases in the levels of antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase), glutathione-S-transferases, reduced glutathione and mitotic index were observed. QE completely and VA partly ameliorated almost of all the examined parameters when given together with CP. Higher total nitrate/nitrite levels were observed in the myocardial tissue treated with QE and VA in combination with CP. In addition, the pre-treatment with VA and QE together with CP significantly decreased chromosome aberrations and aberrant cells compared to CP alone. Results from the current study suggest that QE and VA supplementation attenuates CP induced cardiotoxicity, urotoxicity and genotoxicity through a mechanism related to their ability to decrease oxidative stress and inflammation, and at least in part to its protective effects on the cardiovascular system. In addition, VA and QE may play a role in reducing cytogenotoxicity induced by anti-neoplastic drugs during cancer chemotherapy. PMID:22393965

  13. Protective effects of quercetin and hyperoside on renal fibrosis in rats with unilateral ureteral obstruction

    PubMed Central

    YAN, YANG; FENG, YUAN; LI, WEI; CHE, JIAN-PING; WANG, GUANG-CHUN; LIU, MIN; ZHENG, JUN-HUA

    2014-01-01

    Prevention of renal fibrosis is an important therapeutic strategy in the treatment of obstructive nephropathy. The purpose of the present study was to identify whether the combination of two natural plant-derived flavanoids, quercetin and hyperoside (QH), could inhibit renal fibrosis in the model of unilateral ureteral obstruction (UUO) in rats. QH mixtures (1:1) were fed to Wistar rats, and UUO ligation was performed on all the rats with the exception of the sham group. Masson’s trichrome staining was used for interstitial fibrosis, while immunohistochemistry and western blot analysis were used to detect the expression of α-smooth muscle actin (SMA) and fibronectin (FN). In the QH group, the expression of SMA and FN was significantly lower than that in the untreated UUO group. In addition, QH administration significantly inhibited the SMA and FN expression of mesangial cells induced by interleukin-1β. Consequently, it was evident that combinational QH therapy prevented UUO-induced renal fibrosis. Based on these findings, the combinatorial intervention of phytomedicine may present an improved treatment strategy for renal fibrotic disease. PMID:25120589

  14. Quercetin ameliorates atrazine-induced changes in the testicular function of rats.

    PubMed

    Abarikwu, Sunny O; Farombi, Ebenezer O

    2016-07-01

    The protective effect of quercetin (QT) on atrazine (ATZ)-induced testicular damage in rats was investigated. Sexually mature male Wistar rats (weighing 220-250 g) divided into four groups with six animals in each group were given ATZ (120 mg kg(-1); 1/16 of the median lethal dose for an oral dose) and/or QT (10 mg kg(-1)) daily via gavage for 16 days. By the end of day 16, rats given ATZ alone had significantly lower sperm counts, daily spermatozoa production, and sperm motility and significantly higher abnormal sperm numbers than the untreated control rats. The rats given ATZ alone also had significantly decreased 3β-hydroxtsteroid dehydrogenase (HSD) and 17β-HSD activities than the control rats. Lactate dehydrogenase activity and malondialdehyde levels were significantly increased, whereas superoxide dismutase activity decreased but glutathione levels remain unaffected after ATZ exposure. These changes were reversed toward control values in the QT + ATZ-treated animals, though the sperm motility was 28% below the control levels but was still higher than in the ATZ-treated rats. The results indicate that QT might improve testicular function of rats exposed to ATZ, but its protective effect on sperm motility might be partial. PMID:25427686

  15. Thermoresponsive mesoporous silica nanoparticles as a carrier for skin delivery of quercetin.

    PubMed

    Ugazio, Elena; Gastaldi, Lucia; Brunella, Valentina; Scalarone, Dominique; Jadhav, Sushilkumar A; Oliaro-Bosso, Simonetta; Zonari, Daniele; Berlier, Gloria; Miletto, Ivana; Sapino, Simona

    2016-09-10

    Recently, mesoporous silica nanoparticles (MSNs) have emerged as promising drug delivery systems able to preserve the integrity of the carried substance and/or to selectively reach a target site; however, they have rarely been explored for skin application. In this study, thermoresponsive MSNs, designed to work at physiologic cutaneous temperature, are proposed as innovative topical carriers for quercetin (Q), a well-known antioxidant. The thermosensitive nanoparticles were prepared by functionalizing two different types of matrices, with pore size of 3.5nm (MSNsmall) and 5.0nm (MSNbig), carrying out a free radical copolymerization of N-isopropylacrylamide (NIPAM) and 3-(methacryloxypropyl)trimethoxysilane (MPS) inside the mesopores. The obtained copolymer-grafted MSNs (copoly-MSNs) were physico-chemically characterized and their biocompatibility was attested on a human keratinocyte cell line (HaCaT). The release profiles were assessed and the functional activity of Q, free or loaded, was evaluated in terms of antiradical and metal chelating activities. Ex vivo accumulation and permeation through porcine skin were also investigated. The characterization confirmed the copolymer functionalization of the MSNs. In addition, both the bare and functionalized silica matrices were found to be biocompatible. Among the copolymer-grafted complexes, Q/copoly-MSNbig exhibited more evident thermoresponsive behavior proving the potential of these thermosensitive systems for advanced dermal delivery. PMID:27421910

  16. Prophylactic Efficacy of Quercetin 3-β-O-d-Glucoside against Ebola Virus Infection.

    PubMed

    Qiu, Xiangguo; Kroeker, Andrea; He, Shihua; Kozak, Robert; Audet, Jonathan; Mbikay, Majambu; Chrétien, Michel

    2016-09-01

    Ebola outbreaks occur on a frequent basis, with the 2014-2015 outbreak in West Africa being the largest one ever recorded. This outbreak has resulted in over 11,000 deaths in four African countries and has received international attention and intervention. Although there are currently no approved therapies or vaccines, many promising candidates are undergoing clinical trials, and several have had success in promoting recovery from Ebola. However, these prophylactics and therapeutics have been designed and tested only against the same species of Ebola virus as the one causing the current outbreak. Future outbreaks involving other species would require reformulation and possibly redevelopment. Therefore, a broad-spectrum alternative is highly desirable. We have found that a flavonoid derivative called quercetin 3-β-O-d-glucoside (Q3G) has the ability to protect mice from Ebola even when given as little as 30 min prior to infection. Furthermore, we have demonstrated that this compound targets the early steps of viral entry. Most promisingly, antiviral activity against two distinct species of Ebola virus was seen. This study serves as a proof of principle that Q3G has potential as a prophylactic against Ebola virus infection. PMID:27297486

  17. 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

  18. Quercetin induces apoptosis and enhances 5-FU therapeutic efficacy in hepatocellular carcinoma.

    PubMed

    Dai, Wei; Gao, Quangen; Qiu, Jianping; Yuan, Jianmao; Wu, Guoliang; Shen, Genhai

    2016-05-01

    Quercetin (Q), a flavonoid compound, which is obtained in variety of fruits, seeds, and vegetables, has been reported to possess many pharmacological properties including cancer-preventive and anticancer effects. However, studies on the anticancer effects and underlying mechanisms of Q in human hepatocellular carcinoma (HCC) are still limited. The present study is conducted to investigate the anticancer efficacy and adjuvant chemotherapy action of Q in HCC. HCC cell lines HepG2 and SMCC-7721 were treated with different concentrations of Q. The antiproliferative effects of Q were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), and the apoptosis and cell cycle dynamics were assessed by flow cytometry; the expression of apoptosis-associated proteins were evaluated by Western blot and immunohistochemistry staining; the tumor growth in vivo was evaluated in a xenograft mouse model. Our results showed that Q effectively inhibited human HCC cell proliferation and induced apoptosis by upregulating the expression of Bad and Bax and downregulating the expression of Bcl-2 and Survivin in vitro. Furthermore, Q obviously inhibited the tumor growth and enhanced the 5-fluorouracil (5-FU) therapeutic efficacy in vitro and in vivo. Taken together, our findings highlight that Q effectively inhibited the growth of tumor and enhanced the sensitivity to thermotherapy, indicating Q is a potential treatment option for HCC. PMID:26628295

  19. Effect of quercetin-rich onion peel extracts on arterial thrombosis in rats.

    PubMed

    Lee, Seung-Min; Moon, Jiyoung; Chung, Ji Hyung; Cha, Yong-Jun; Shin, Min-Jeong

    2013-07-01

    The aim of this study was to examine whether oral supplementation of quercetin-rich onion peel extract (OPE) influences blood coagulation and arterial thrombosis in Sprague-Dawley (SD) rats. 24 male rats, 5 weeks old, were divided into three groups with different diets (C: control, 2mg OPE: chow diet with 2mg OPE supplementation, 10mg OPE: chow diet with 10mg OPE supplementation) for 6 weeks. Blood coagulation parameters including prothrombin time (PT), activated partial thromboplastin time (aPTT) and platelet aggregation were examined. The OPE did not affect blood cholesterol levels but significantly decreased blood triglyceride and glucose levels. PT, aPTT and platelet aggregation were not significantly different among all tested groups. However, in vivo arterial thrombosis was significantly delayed in groups that were fed 2mg and 10mg OPE diets compared to the control group. In addition, the OPE greatly diminished thrombin-induced expression of tissue factor in human umbilical vein endothelial cells (HUVECs), a coagulation initiator. In addition, extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) signaling pathways activated by thrombin treatment were prevented by the OPE pre-treatment. These results indicate that OPE may have anti-thrombotic effects through restricting the induced expression of tissue factor via down-regulating mitogen-activated protein kinase (MAPK) activation upon coagulation stimulus, leading to the prolongation of time for arterial thrombosis. PMID:23524316

  20. Quercetin Suppresses the Migration and Invasion in Human Colon Cancer Caco-2 Cells Through Regulating Toll-like Receptor 4/Nuclear Factor-kappa B Pathway

    PubMed Central

    Han, Mingyang; Song, Yucheng; Zhang, Xuedong

    2016-01-01

    Objective: The migration and invasion features, which were associated with inflammatory response, acted as vital roles in the development of colon cancer. Quercetin, a bioflavonoid compound, was widely spread in vegetables and fruits. Although quercetin exerts antioxidant and anticancer activities, the molecular signaling pathways in human colon cancer cells remain unclear. Hence, the present study was conducted to investigate the suppression of quercetin on migratory and invasive activity of colon cancer and the underlying mechanism. Materials and Methods: The effect of quercetin on cell viability, migration, and invasion of Caco-2 cells was analyzed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, wound-healing assay, and transwell chambers assay, respectively. The protein expressions of toll-like receptor 4 (TLR4), nuclear factor-kappa B (NF-κB) p65, mitochondrial membrane potential-2 (MMP-2), and MMP-9 were detected by Western blot assay. The inflammatory factors, such as tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (Cox-2), and interleukin-6 (IL-6), in cell supernatant were detected by enzyme-linked immunosorbent assay. Results: The concentration of quercetin <20 μM was chosen for further experiments. Quercetin (5 μM) could remarkably suppress the migratory and invasive capacity of Caco-2 cells. The expressions of metastasis-related proteins of MMP-2, MMP-9 were decreased, whereas the expression of E-cadherin protein was increased by quercetin in a dose-dependent manner. Interestingly, the anti-TLR4 (2 μg) antibody or pyrrolidine dithiocarbamate (PDTC; 1 μM) could affect the inhibition of quercetin on cell migration and invasion, as well as the protein expressions of MMP-2, MMP-9, E-cadherin, TLR4, and NF-κB p65. In addition, quercetin could reduce the inflammation factors production of TNF-α, Cox-2, and IL-6. Conclusion: The findings suggested for the 1st time that quercetin might exert its anticolon cancer activity via

  1. 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

  2. Quercetin Attenuates Inflammatory Responses in BV-2 Microglial Cells: Role of MAPKs on the Nrf2 Pathway and Induction of Heme Oxygenase-1

    PubMed Central

    Sun, Grace Y.; Chen, Zihong; Jasmer, Kimberly J.; Chuang, Dennis Y.; Gu, Zezong; Hannink, Mark; Simonyi, Agnes

    2015-01-01

    A large group of flavonoids found in fruits and vegetables have been suggested to elicit health benefits due mainly to their anti-oxidative and anti-inflammatory properties. Recent studies with immune cells have demonstrated inhibition of these inflammatory responses through down-regulation of the pro-inflammatory pathway involving NF-κB and up-regulation of the anti-oxidative pathway involving Nrf2. In the present study, the murine BV-2 microglial cells were used to compare anti-inflammatory activity of quercetin and cyanidin, two flavonoids differing by their alpha, beta keto carbonyl group. Quercetin was 10 folds more potent than cyanidin in inhibition of lipopolysaccharide (LPS)-induced NO production as well as stimulation of Nrf2-induced heme-oxygenase-1 (HO-1) protein expression. In addition, quercetin demonstrated enhanced ability to stimulate HO-1 protein expression when cells were treated with LPS. In an attempt to unveil mechanism(s) for quercetin to enhance Nrf2/HO-1 activity under endotoxic stress, results pointed to an increase in phospho-p38MAPK expression upon addition of quercetin to LPS. In addition, pharmacological inhibitors for phospho-p38MAPK and MEK1/2 for ERK1/2 further showed that these MAPKs target different sites of the Nrf2 pathway that regulates HO-1 expression. However, inhibition of LPS-induced NO by quercetin was not fully reversed by TinPPIX, a specific inhibitor for HO-1 activity. Taken together, results suggest an important role of quercetin to regulate inflammatory responses in microglial cells and its ability to upregulate HO-1 against endotoxic stress through involvement of MAPKs. PMID:26505893

  3. Reshaping faecal gut microbiota composition by the intake of trans-resveratrol and quercetin in high-fat sucrose diet-fed rats.

    PubMed

    Etxeberria, U; Arias, N; Boqué, N; Macarulla, M T; Portillo, M P; Martínez, J A; Milagro, F I

    2015-06-01

    Diet-induced obesity is associated to an imbalance in the normal gut microbiota composition. Resveratrol and quercetin, widely known for their health beneficial properties, have low bioavailability, and when they reach the colon, they are targets of the gut microbial ecosystem. Hence, the use of these molecules in obesity might be considered as a potential strategy to modulate intestinal bacterial composition. The purpose of this study was to determine whether trans-resveratrol and quercetin administration could counteract gut microbiota dysbiosis produced by high-fat sucrose diet (HFS) and, in turn, improve gut health. Wistar rats were randomised into four groups fed an HFS diet supplemented or not with trans-resveratrol [15 mg/kg body weight (BW)/day], quercetin (30 mg/kg BW/day) or a combination of both polyphenols at those doses. Administration of both polyphenols together prevented body weight gain and reduced serum insulin levels. Moreover, individual supplementation of trans-resveratrol and quercetin effectively reduced serum insulin levels and insulin resistance. Quercetin supplementation generated a great impact on gut microbiota composition at different taxonomic levels, attenuating Firmicutes/Bacteroidetes ratio and inhibiting the growth of bacterial species previously associated to diet-induced obesity (Erysipelotrichaceae, Bacillus, Eubacterium cylindroides). Overall, the administration of quercetin was found to be effective in lessening HFS-diet-induced gut microbiota dysbiosis. In contrast, trans-resveratrol supplementation alone or in combination with quercetin scarcely modified the profile of gut bacteria but acted at the intestinal level, altering the mRNA expression of tight-junction proteins and inflammation-associated genes. PMID:25762527

  4. Hepatoprotective Effect of Quercetin on Endoplasmic Reticulum Stress and Inflammation after Intense Exercise in Mice through Phosphoinositide 3-Kinase and Nuclear Factor-Kappa B

    PubMed Central

    Tang, Yuhan; Li, Juan; Gao, Chao; Xu, Yanyan; Li, Yanyan; Yu, Xiao; Wang, Jing; Liu, Liegang

    2016-01-01

    The mechanisms underlying intense exercise-induced liver damage and its potential treatments remain unclear. We explored the hepatoprotection and mechanisms of quercetin, a naturally occurring flavonoid, in strenuous exercise-derived endoplasmic reticulum stress (ERS) and inflammation. Intense exercise (28 m/min at a 5° slope for 90 min) resulted in the leakage of aminotransferases in the BALB/C mice. The hepatic ultrastructural malformations and oxidative stress levels were attenuated by quercetin (100 mg/kg·bw). Intense exercise and thapsigargin- (Tg-) induced ERS (glucose-regulated protein 78, GRP78) and inflammatory cytokines levels (IL-6 and TNF-α) were decreased with quercetin. Furthermore, quercetin resulted in phosphoinositide 3-kinase (PI3K) induction, Ca2+ restoration, and blockade of the activities of Jun N-terminal kinase (JNK), activating transcription factor 6 (ATF6) and especially NF-κB (p65 and p50 nuclear translocation). A PI3K inhibitor abrogated the protection of quercetin on ERS and inflammation of mouse hepatocytes. SP600125 (JNK inhibitor), AEBSF (ATF6 inhibitor), and especially PDTC (NF-κB inhibitor) enhanced the quercetin-induced protection against Tg stimulation. Collectively, intense exercise-induced ERS and inflammation were attenuated by quercetin. PI3K/Akt activation and JNK, ATF6, and especially NF-κB suppression were involved in the protection. Our results highlight a novel preventive strategy for treating ERS and inflammation-mediated liver damage induced by intense exercise using natural phytochemicals. PMID:27504150

  5. Quercetin ameliorates ischemia/reperfusion-induced cognitive deficits by inhibiting ASK1/JNK3/caspase-3 by enhancing the Akt signaling pathway.

    PubMed

    Pei, Bing; Yang, Miaomiao; Qi, Xiaoyan; Shen, Xin; Chen, Xing; Zhang, Fayong

    2016-09-01

    Cerebral ischemia/reperfusion (I/R) is a major cause of severe disability and death all worldwide. However, therapeutic options to minimize the detrimental effects of cerebral I/R injury are limited. Recent research has demonstrated that quercetin mediates neuroprotective effects associated with the activation of the Akt signaling pathway in the cerebral I/R brain. Therefore, the aim of this study was to further investigate the mechanisms of cognitive deficits induced by cerebral I/R injury and the effects of quercetin on these mechanisms. First, we assessed anxiety-like behavioral and cognitive impairment using the open field test and the Morris water maze test, respectively. Next, we examined the severity of apoptosis by staining hippocampal neurons by the Cresyl violet method. Third, we used western blot analysis to investigate the expression of total and phosphorylated Akt, ASK1, JNK3, c-Jun and caspase-3 after I/R injury. Our results revealed that mice subjected to bilateral common carotid occlusion exhibited severe anxiety-like behavior, learning and memory impairment, cell damage and apoptosis. These severe effects were attenuated by administration of quercetin. Further, western blot analysis revealed that quercetin increased p-Akt expression and decreased p-ASK1, p-JNK3 and cleaved caspase-3 expression after cerebral I/R injury and led to inhibition of neuronal apoptosis. Conversely, treatment with LY294002 (a selective inhibitor of Akt1) reversed the effects of quercetin. In conclusion, these findings highlight the important role of quercetin in protecting against cognitive deficits and inhibiting neuronal apoptosis via the Akt signaling pathway. We believe that quercetin might prove to be a useful therapeutic component in treating cerebral I/R diseases in the near future. PMID:27450812

  6. Hepatoprotective Effect of Quercetin on Endoplasmic Reticulum Stress and Inflammation after Intense Exercise in Mice through Phosphoinositide 3-Kinase and Nuclear Factor-Kappa B.

    PubMed

    Tang, Yuhan; Li, Juan; Gao, Chao; Xu, Yanyan; Li, Yanyan; Yu, Xiao; Wang, Jing; Liu, Liegang; Yao, Ping

    2016-01-01

    The mechanisms underlying intense exercise-induced liver damage and its potential treatments remain unclear. We explored the hepatoprotection and mechanisms of quercetin, a naturally occurring flavonoid, in strenuous exercise-derived endoplasmic reticulum stress (ERS) and inflammation. Intense exercise (28 m/min at a 5° slope for 90 min) resulted in the leakage of aminotransferases in the BALB/C mice. The hepatic ultrastructural malformations and oxidative stress levels were attenuated by quercetin (100 mg/kg·bw). Intense exercise and thapsigargin- (Tg-) induced ERS (glucose-regulated protein 78, GRP78) and inflammatory cytokines levels (IL-6 and TNF-α) were decreased with quercetin. Furthermore, quercetin resulted in phosphoinositide 3-kinase (PI3K) induction, Ca(2+) restoration, and blockade of the activities of Jun N-terminal kinase (JNK), activating transcription factor 6 (ATF6) and especially NF-κB (p65 and p50 nuclear translocation). A PI3K inhibitor abrogated the protection of quercetin on ERS and inflammation of mouse hepatocytes. SP600125 (JNK inhibitor), AEBSF (ATF6 inhibitor), and especially PDTC (NF-κB inhibitor) enhanced the quercetin-induced protection against Tg stimulation. Collectively, intense exercise-induced ERS and inflammation were attenuated by quercetin. PI3K/Akt activation and JNK, ATF6, and especially NF-κB suppression were involved in the protection. Our results highlight a novel preventive strategy for treating ERS and inflammation-mediated liver damage induced by intense exercise using natural phytochemicals. PMID:27504150

  7. Quercetin inhibits angiogenesis through thrombospondin-1 upregulation to antagonize human prostate cancer PC-3 cell growth in vitro and in vivo.

    PubMed

    Yang, Feiya; Jiang, Xian; Song, Liming; Wang, Huiping; Mei, Zhu; Xu, Zhiqing; Xing, Nianzeng

    2016-03-01

    The rapid growth, morbidity and mortality of prostate cancer, and the lack of effective treatment have attracted great interests of researchers to find novel cancer therapies aiming to inhibit angiogenesis and tumor growth. Quercetin is a flavonoid compound that widely exists in the nature. Our previous study preliminarily demonstrated that quercetin effectively inhibited human prostate cancer cell xenograft tumor growth by inhibiting angiogenesis. Thrombospondin-1 (TSP-1) is the first reported endogenous anti-angiogenic factor that can inhibit angiogenesis and tumorigenesis. However, the relationship between quercetin inhibiting angiogenesis and TSP-1 upregulation in prostate cancer has not been determined. Thus, we explored the important role of TSP-1 upregulation in reducing angiogenesis and anti-prostate cancer effect of quercetin both in vitro and in vivo for the first time. After the selected doses were used for a certain time, quercetin i) significantly inhibited PC-3 and human umbilical vein endothelial cells (HUVECs) proliferation, migration and invasion in a dose-dependent manner; ⅱ) effectively inhibited prostate cancer PC-3 cell xenograft tumor growth by 37.5% with 75 mg/kg as compared to vehicle control group, more effective than 25 (22.85%) and 50 mg/kg (29.6%); ⅲ) was well tolerated by BALB/c mice and no obvious toxic reactions were observed; ⅳ) greatly reduced angiogenesis and led to higher TSP-1 protein and mRNA expression both in vitro and in vivo in a dose-dependent manner. Therefore, quercetin could increase TSP-1 expression to inhibit angiogenesis resulting in antagonizing prostate cancer PC-3 cell and xenograft tumor growth. The present study can lay a good basis for the subsequent concrete mechanism study and raise the possibility of applying quercetin to clinical for human prostate cancer in the near future. PMID:26676551

  8. Quercetin Protects against Okadaic Acid-Induced Injury via MAPK and PI3K/Akt/GSK3β Signaling Pathways in HT22 Hippocampal Neurons.

    PubMed

    Jiang, Wei; Luo, Tao; Li, Sheng; Zhou, Yue; Shen, Xiu-Yin; He, Feng; Xu, Jie; Wang, Hua-Qiao

    2016-01-01

    Increasing evidence shows that oxidative stress and the hyperphosphorylation of tau protein play essential roles in the progression of Alzheimer's disease (AD). Quercetin is a major flavonoid that has anti-oxidant, anti-cancer and anti-inflammatory properties. We investigated the neuroprotective effects of quercetin to HT22 cells (a cell line from mouse hippocampal neurons). We found that Okadaic acid (OA) induced the hyperphosphorylation of tau protein at Ser199, Ser396, Thr205, and Thr231 and produced oxidative stress to the HT22 cells. The oxidative stress suppressed the cell viability and decreased the levels of lactate dehydrogenase (LDH), superoxide dismutase (SOD), mitochondria membrane potential (MMP) and Glutathione peroxidase (GSH-Px). It up-regulated malondialdehyde (MDA) production and intracellular reactive oxygen species (ROS). In addition, phosphoinositide 3 kinase/protein kinase B/Glycogen synthase kinase3β (PI3K/Akt/GSK3β) and mitogen activated protein kinase (MAPK) were also involved in this process. We found that pre-treatment with quercetin can inhibited OA-induced the hyperphosphorylation of tau protein and oxidative stress. Moreover, pre-treatment with quercetin not only inhibited OA-induced apoptosis via the reduction of Bax, and up-regulation of cleaved caspase 3, but also via the inhibition of PI3K/Akt/GSK3β, MAPKs and activation of NF-κB p65. Our findings suggest the therapeutic potential of quercetin to treat AD. PMID:27050422

  9. Quercetin Alleviates High-Fat Diet-Induced Oxidized Low-Density Lipoprotein Accumulation in the Liver: Implication for Autophagy Regulation

    PubMed Central

    Liu, Liang; Gao, Chao; Yao, Ping; Gong, Zhiyong

    2015-01-01

    A growing body of evidence has indicated that high-fat diet-induced nonalcoholic fatty liver disease is usually accompanied by oxidized low-density lipoprotein (ox-LDL) deposited in the liver. The current study aimed to investigate the effect of quercetin on high-fat diet-induced ox-LDL accumulation in the liver and to explore the potential underlying mechanisms. The results demonstrate that quercetin supplementation for 24 weeks significantly alleviated high-fat diet-induced liver damage and reduced hepatic cholesterol and ox-LDL level. Quercetin notably inhibited both mRNA and protein expression of CD36 (reduced by 53% and 71%, resp.) and MSR1 (reduced by 25% and 45%, resp.), which were upregulated by high-fat diet. The expression of LC3II was upregulated by 2.4 times whereas that of p62 and mTOR was downregulated by 57% and 63% by quercetin treatment. Therefore, the significantly improved autophagy lysosomal degradation capacity for ox-LDL may be implicated in the hepatoprotective effect of quercetin; scavenger receptors mediated ox-LDL uptake might also be involved. PMID:26697490

  10. Synthesis of methylated quercetin derivatives and their reversal activities on P-gp- and BCRP-mediated multidrug resistance tumour cells.

    PubMed

    Yuan, Jian; Wong, Iris L K; Jiang, Tao; Wang, Si Wen; Liu, Tao; Wen, Bin Jin; Chow, Larry M C; Wan Sheng, Biao

    2012-08-01

    Three methylated quercetins and a series of O-3 substituted 5,7,3',4'-tetra-O-methylated quercetin derivatives have been synthesized and evaluated on the modulating activity of P-gp, BCRP and MRP1 in cancer cell lines. Compound 17 (with a 2-((4-methoxybenzoyl)oxy)ethyl at O-3) is the most potent P-gp modulator. Three derivatives, compound 9 (3,7,3',4'-tetra-O-methylated quercetin), compound 14 (with a 2-((3-oxo-3-(3,4,5trimethoxyphenyl)prop-1-en-1-yl)oxy)ethyl at O-3) and compound 17, consistently exhibited promising BCRP-modulating activity. Interestingly, compound 17 was found to be equipotent against both P-gp and BCRP. Importantly, these synthetic quercetin derivatives did not exhibit any inherent cytotoxicity to cancer cell lines or normal mouse fibroblast cell lines. These quercetin derivatives can be employed as safe and effective modulators of P-gp- or BCRP-mediated drug resistance in cancer. PMID:22743241

  11. Quercetin Protects against Okadaic Acid-Induced Injury via MAPK and PI3K/Akt/GSK3β Signaling Pathways in HT22 Hippocampal Neurons

    PubMed Central

    Li, Sheng; Zhou, Yue; Shen, Xiu-Yin; He, Feng; Xu, Jie; Wang, Hua-Qiao

    2016-01-01

    Increasing evidence shows that oxidative stress and the hyperphosphorylation of tau protein play essential roles in the progression of Alzheimer’s disease (AD). Quercetin is a major flavonoid that has anti-oxidant, anti-cancer and anti-inflammatory properties. We investigated the neuroprotective effects of quercetin to HT22 cells (a cell line from mouse hippocampal neurons). We found that Okadaic acid (OA) induced the hyperphosphorylation of tau protein at Ser199, Ser396, Thr205, and Thr231 and produced oxidative stress to the HT22 cells. The oxidative stress suppressed the cell viability and decreased the levels of lactate dehydrogenase (LDH), superoxide dismutase (SOD), mitochondria membrane potential (MMP) and Glutathione peroxidase (GSH-Px). It up-regulated malondialdehyde (MDA) production and intracellular reactive oxygen species (ROS). In addition, phosphoinositide 3 kinase/protein kinase B/Glycogen synthase kinase3β (PI3K/Akt/GSK3β) and mitogen activated protein kinase (MAPK) were also involved in this process. We found that pre-treatment with quercetin can inhibited OA-induced the hyperphosphorylation of tau protein and oxidative stress. Moreover, pre-treatment with quercetin not only inhibited OA-induced apoptosis via the reduction of Bax, and up-regulation of cleaved caspase 3, but also via the inhibition of PI3K/Akt/GSK3β, MAPKs and activation of NF-κB p65. Our findings suggest the therapeutic potential of quercetin to treat AD. PMID:27050422

  12. Enhanced formation of quercetin by combined use of gamma ray and H2O2 from cyanidin-3-O-xylosylrutinoside

    NASA Astrophysics Data System (ADS)

    Lee, Seung Sik; Lee, Eun Mi; Hong, Sung Hyun; Yoo, Sang-Ho; Cho, Jae-Young; Lee, In Chul; Chung, Byung Yeoup

    2012-08-01

    Cyanidin-3-O-xylosylrutinoside (cya-3-O-xylrut), a major pigment in Schizandra chinensis Baillon, was effectively removed by gamma irradiation of greater than 2 kGy, whereas quercetin, the most abundant of the flavonoids and has anti-inflammatory and anti-allergic effects, could be generated by degradation of cya-3-O-xylrut. In the present study, we investigated the effect of combination treatment of gamma irradiation and hydrogen peroxide (H2O2) on the formation of quercetin through the degradation of cya-3-O-xylrut. Cya-3-O-xylrut was significantly degraded (˜93%) by gamma irradiation at 2 kGy and it was completely removed by a combination treatment (0.2% H2O2 and 2 kGy gamma ray). The formation of quercetin was significantly appeared at 2 kGy of gamma ray, together with disappearance of cya-3-O-xylrut. The quercetin formation by gamma ray is 3.2 μg/ml and combination treatment is 7.7 μg/ml. Therefore, the combination treatment of H2O2 and gamma ray is more effective to convert cya-3-O-xylrut into quercetin than gamma irradiation only. In conclusion, gamma ray combined with H2O2 would be a promising tool for bio-conversion of organic compounds.

  13. Simultaneous Analysis of Quercetin and Naringenin in Rat Plasma by Liquid Chromatography-Tandem Mass Spectrometry: Application to a Pharmacokinetic Study After Oral Administration.

    PubMed

    Ni, Boran; Cao, Sali; Feng, Lijun; Yin, Xingbin; Wang, Wenping; Zhang, Xin; Ni, Jian

    2016-09-01

    A rapid and specific LC-MS-MS method has been developed for simultaneous analysis of quercetin and naringenin in rat plasma. The method was applied to the pharmacokinetics studies of quercetin and naringenin after oral administration of Pollen Typhae extract. The samples were prepared by the protein precipitation method. The analysis was carried out on an ACQUITY UPLC™ BEH C18 column with gradient elution using mobile phase, which included acetonitrile and water (containing 0.1% formic acid). The flow rate was 0.4 mL/min. All analytes including internal standard (IS) were monitored by selected reaction monitoring with an electrospray ionization source. Linear responses were obtained for quercetin ranging from 0.5 to 100 ng/mL and naringenin ranging from 5 to 1000 ng/mL. The intra- and interday precisions (RSD) were less than 10.78 and 11.20%. The extraction recovery of the analytes was acceptable. Stability studies showed that quercetin and naringenin were stable in the preparation and analytical process. The validated method was successfully used to determine the concentration-time profiles of quercetin and naringenin. PMID:27199443

  14. Protective Effects of Quercetin Against HgCl₂-Induced Nephrotoxicity in Sprague-Dawley Rats.

    PubMed

    Shin, Yu Jin; Kim, Jeong Jun; Kim, Ye Ji; Kim, Won Hee; Park, Eun Young; Kim, In Young; Shin, Han-Seung; Kim, Kyeong Seok; Lee, Eui-Kyung; Chung, Kyu Hyuck; Lee, Byung Mu; Kim, Hyung Sik

    2015-05-01

    Mercury is a well-known environmental pollutant that can cause nephropathic diseases, including acute kidney injury (AKI). Although quercetin (QC), a natural flavonoid, has been reported to have medicinal properties, its potential protective effects against mercury-induced AKI have not been evaluated. In this study, the protective effect of QC against mercury-induced AKI was investigated using biochemical parameters, new protein-based urinary biomarkers, and a histopathological approach. A 250 mg/kg dose of QC was administered orally to Sprague-Dawley male rats for 3 days before administration of mercury chloride (HgCl2). All animals were sacrificed at 24 h after HgCl2 treatment, and biomarkers associated with nephrotoxicity were measured. Our data showed that QC absolutely prevented HgCl2-induced AKI, as indicated by biochemical parameters such as blood urea nitrogen (BUN) and serum creatinine (sCr). In particular, QC markedly decreased the accumulation of Hg in the kidney. Urinary excretion of protein-based biomarkers, including clusterin, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), monocyte chemoattractant protein-1 (MCP-1), tissue inhibitor of metalloproteinases 1 (TIMP-1), and vascular endothelial growth factor (VEGF) in response to HgCl2 administration were significantly decreased by QC pretreatment relative to that in the HgCl2-treated group. Furthermore, urinary excretion of metallothionein and Hg were significantly elevated by QC pretreatment. Histopathological examination indicated that QC protected against HgCl2-induced proximal tubular damage in the kidney. A TUNEL assay indicated that QC pretreatment significantly reduced apoptotic cell death in the kidney. The administration of QC provided significant protective effects against mercury-induced AKI. PMID:25692400

  15. Quercetin Sensitizes Fluconazole-Resistant Candida albicans To Induce Apoptotic Cell Death by Modulating Quorum Sensing

    PubMed Central

    Singh, B. R.; Pandey, G.; Verma, S.; Roy, S.; Naqvi, A. H.

    2015-01-01

    Quorum sensing (QS) regulates group behaviors of Candida albicans such as biofilm, hyphal growth, and virulence factors. The sesquiterpene alcohol farnesol, a QS molecule produced by C. albicans, is known to regulate the expression of virulence weapons of this fungus. Fluconazole (FCZ) is a broad-spectrum antifungal drug that is used for the treatment of C. albicans infections. While FCZ can be cytotoxic at high concentrations, our results show that at much lower concentrations, quercetin (QC), a dietary flavonoid isolated from an edible lichen (Usnea longissima), can be implemented as a sensitizing agent for FCZ-resistant C. albicans NBC099, enhancing the efficacy of FCZ. QC enhanced FCZ-mediated cell killing of NBC099 and also induced cell death. These experiments indicated that the combined application of both drugs was FCZ dose dependent rather than QC dose dependent. In addition, we found that QC strongly suppressed the production of virulence weapons—biofilm formation, hyphal development, phospholipase, proteinase, esterase, and hemolytic activity. Treatment with QC also increased FCZ-mediated cell death in NBC099 biofilms. Interestingly, we also found that QC enhances the anticandidal activity of FCZ by inducing apoptotic cell death. We have also established that this sensitization is reliant on the farnesol response generated by QC. Molecular docking studies also support this conclusion and suggest that QC can form hydrogen bonds with Gln969, Thr1105, Ser1108, Arg1109, Asn1110, and Gly1061 in the ATP binding pocket of adenylate cyclase. Thus, this QS-mediated combined sensitizer (QC)-anticandidal agent (FCZ) strategy may be a novel way to enhance the efficacy of FCZ-based therapy of C. albicans infections. PMID:25645848

  16. Effect of Antioxidant Flavonoids (Quercetin and Taxifolin) on In vitro Maturation of Porcine Oocytes

    PubMed Central

    Kang, Jung-Taek; Moon, Joon Ho; Choi, Ji-Yei; Park, Sol Ji; Kim, Su Jin; Saadeldin, Islam M.; Lee, Byeong Chun

    2016-01-01

    Quercetin (QT) and taxifolin (TF) are structurally similar plant-derived flavonoids that have antioxidant properties and act as free radical scavengers. The objective of this study was to investigate effects of QT and TF on nuclear maturation of porcine oocytes. Effects of TF at 0, 1, 10, and 50 μg/mL on oocyte nuclear maturation (polar body extrusion) were investigated. After incubation for 44 h, there were no significant differences between the treatment and control groups except in the 50 μg/mL group which was significantly lower (59.2%, p<0.05) than the other groups (control: >80%). After parthenogenetic activation, further in vitro development of QT- or TF-treated vs control oocytes was investigated. A significantly higher proportion of QT-treated (1 μg/mL) oocytes developed into blastocysts compared to controls (24.3% vs 16.8%, respectively); however, cleavage rate and blastocyst cell number were not affected. The TF-treated group was not significantly different from controls. Levels of reactive oxygen species (ROS) and intracellular glutathione (GSH) in oocytes and embryos in a culture medium supplemented with QT or TF were measured. Both treatment groups had significantly lower (p<0.05) levels of ROS than controls, however GSH levels were different only in QT-treated oocytes. We conclude that exogenous flavonoids such as QT and TF reduce ROS levels in oocytes. Although at high concentration (50 μg/mL) both QT and TF appear to be toxic to oocytes. PMID:26950865

  17. Evaluation of combined famotidine with quercetin for the treatment of peptic ulcer: in vivo animal study

    PubMed Central

    Abourehab, Mohammed AS; Khaled, Khaled A; Sarhan, Hatem AA; Ahmed, Osama AA

    2015-01-01

    The aim of this work was to prepare a combined drug dosage form of famotidine (FAM) and quercetin (QRT) to augment treatment of gastric ulcer. FAM was prepared as freeze-dried floating alginate beads using ion gelation method and then coated with Eudragit RL100 to sustain FAM release. QRT was prepared as solid dispersion with polyvinyl pyrrolidone K30 to improve its solubility. Photo images and scanning electron microscope images of the prepared beads were carried out to detect floating behavior and to reveal surface and core shape of the prepared beads. Anti-ulcerogenic effect and histopathological examination of gastric tissues were carried out to investigate the effect of the combined drug formulation compared with commercial FAM tablets and FAM beads. Gastric glutathione (GSH), superoxide dismutase, catalase, tissue myeloperoxidase, and lipid peroxidation enzyme activities and levels in rat stomach tissues were also determined. Results revealed that spherical beads were formed with an average diameter of 1.64±0.33 mm. They floated immediately with no lag time before floating, and remained buoyant throughout the test period. Treatment with a combination of FAM beads plus QRT showed the absence of any signs of inflammation or hemorrhage, and significantly prevented the indomethacin-induced decrease in GSH levels (P<0.05) with regain of normal GSH gastric tissue levels. Also, there was a significant difference in the decrease of malondialdehyde level compared to FAM commercial tablets or beads alone (P<0.05). The combined formula significantly improved the myeloperoxidase level compared to both the disease control group and commercial FAM tablet-treated group (P<0.05). Formulation of FAM as floating beads in combination with solid dispersion of QRT improved the anti-ulcer activity compared to commercially available tablets, which reveals a promising application for treatment of peptic ulcer. PMID:25926722

  18. Quercetin alleviates myocyte toxic and sensitizes anti-leukemic effect of adriamycin.

    PubMed

    Han, Yanqiu; Yu, Hong; Wang, Junrui; Ren, Yanzhen; Su, Xiulan; Shi, Yingxu

    2015-06-01

    Objectives Derived from plants, flavonoids have been proven to possess anti-cancer activities. Adriamycin (ADM), an anthracycline antibiotic, is widely applied in the chemotherapy for leukemia; however, it has a side effect of heart damage. This study aims to explore potential anti-leukemia effects of quercetin (Que) and the underlying mechanism. Methods The P388 xenograft mice models were first established and then treated with Que alone or in combination with ADM. Subsequently, we evaluated their effects on cell proliferation and apoptosis by observing the cell cycle and detecting the Caspase-3 level, respectively. The underlying pro-apoptotic mechanism was further investigated by detecting the expression levels of NF-κB, Bcl-2, and Bax. The cardiomyocyte ultrastructural changes of P388 leukemic mice after drug treatment were also observed. The protective effect of Que on cardiomyocyte was evaluated by detecting enzymatic activity changes of glutathione peroxidase, superoxide dismutase, and malondialdehyde. Results Compared with ADM group, the combination of ADM and Que showed prolonged survival time and less peripheral white blood cells. Que could sensitize the anti-leukemic effect of ADM by inhibiting the proliferation of white blood cells through trapping the cells at the S phase; caspase-3 was activated via the expressional regulation of Bcl-2, Bax, and NF-κB. When applied in combination with ADM, Que could attenuate heart damage by cleaning the reactive oxygen species. Conclusion Our study may provide informative evidences for the underlying mechanism of anti-cancer effects of Que and sheds light on the clinical application of Que in leukemia treatment. PMID:25201038

  19. Prophylactic effects of quercetin and hyperoside in a calcium oxalate stone forming rat model.

    PubMed

    Zhu, Wei; Xu, Yun-fei; Feng, Yuan; Peng, Bo; Che, Jian-ping; Liu, Min; Zheng, Jun-hua

    2014-12-01

    Quercetin and hyperoside (QH) are the two main constituents of the total flavone glycosides of Flos Abelmoschus manihot, which has been prescribed for treating chronic kidney disease for decades. This study aimed to investigate the effect of QH on calcium oxalate (CaOx) formation in ethylene glycol (EG)-fed rats. Rats were divided into three groups: an untreated stone-forming group, a QH-treated stone-forming group (20 mg/kg/day) and a potassium citrate-treated stone-forming group (potassium citrate was a worldwide-recognized calculi-prophylactic medicine). Ethylene glycol (0.5 %) was administered to the rats during the last week, and vitamin D3 was force-fed to induce hyperoxaluria and kidney calcium oxalate crystal deposition. 24 h urine samples were collected before and after inducing crystal deposits. Rats were killed and both kidneys were harvested after 3 weeks. Bisected kidneys were examined under a polarized light microscope for semi-quantification of the crystal-formation. The renal tissue superoxide dismutase and catalase levels were measured by Western blot. QH and potassium citrate have the ability to alkalinize urine. The number of crystal deposits decreased significantly in the QH-treated stone-forming group as compared to the other groups. Superoxide dismutase and catalase levels also increased significantly in the QH-treated stone-forming group, as compared with the untreated stone-forming group. QH administration has an inhibitory effect on the deposition of CaOx crystal in EG-fed rats and may be effective for preventing stone-forming disease. PMID:25085199

  20. Evaluation of combined famotidine with quercetin for the treatment of peptic ulcer: in vivo animal study.

    PubMed

    Abourehab, Mohammed A S; Khaled, Khaled A; Sarhan, Hatem A A; Ahmed, Osama A A

    2015-01-01

    The aim of this work was to prepare a combined drug dosage form of famotidine (FAM) and quercetin (QRT) to augment treatment of gastric ulcer. FAM was prepared as freeze-dried floating alginate beads using ion gelation method and then coated with Eudragit RL100 to sustain FAM release. QRT was prepared as solid dispersion with polyvinyl pyrrolidone K30 to improve its solubility. Photo images and scanning electron microscope images of the prepared beads were carried out to detect floating behavior and to reveal surface and core shape of the prepared beads. Anti-ulcerogenic effect and histopathological examination of gastric tissues were carried out to investigate the effect of the combined drug formulation compared with commercial FAM tablets and FAM beads. Gastric glutathione (GSH), superoxide dismutase, catalase, tissue myeloperoxidase, and lipid peroxidation enzyme activities and levels in rat stomach tissues were also determined. Results revealed that spherical beads were formed with an average diameter of 1.64±0.33 mm. They floated immediately with no lag time before floating, and remained buoyant throughout the test period. Treatment with a combination of FAM beads plus QRT showed the absence of any signs of inflammation or hemorrhage, and significantly prevented the indomethacin-induced decrease in GSH levels (P<0.05) with regain of normal GSH gastric tissue levels. Also, there was a significant difference in the decrease of malondialdehyde level compared to FAM commercial tablets or beads alone (P<0.05). The combined formula significantly improved the myeloperoxidase level compared to both the disease control group and commercial FAM tablet-treated group (P<0.05). Formulation of FAM as floating beads in combination with solid dispersion of QRT improved the anti-ulcer activity compared to commercially available tablets, which reveals a promising application for treatment of peptic ulcer. PMID:25926722

  1. Quercetin sensitizes fluconazole-resistant candida albicans to induce apoptotic cell death by modulating quorum sensing.

    PubMed

    Singh, B N; Upreti, D K; Singh, B R; Pandey, G; Verma, S; Roy, S; Naqvi, A H; Rawat, A K S

    2015-04-01

    Quorum sensing (QS) regulates group behaviors of Candida albicans such as biofilm, hyphal growth, and virulence factors. The sesquiterpene alcohol farnesol, a QS molecule produced by C. albicans, is known to regulate the expression of virulence weapons of this fungus. Fluconazole (FCZ) is a broad-spectrum antifungal drug that is used for the treatment of C. albicans infections. While FCZ can be cytotoxic at high concentrations, our results show that at much lower concentrations, quercetin (QC), a dietary flavonoid isolated from an edible lichen (Usnea longissima), can be implemented as a sensitizing agent for FCZ-resistant C. albicans NBC099, enhancing the efficacy of FCZ. QC enhanced FCZ-mediated cell killing of NBC099 and also induced cell death. These experiments indicated that the combined application of both drugs was FCZ dose dependent rather than QC dose dependent. In addition, we found that QC strongly suppressed the production of virulence weapons-biofilm formation, hyphal development, phospholipase, proteinase, esterase, and hemolytic activity. Treatment with QC also increased FCZ-mediated cell death in NBC099 biofilms. Interestingly, we also found that QC enhances the anticandidal activity of FCZ by inducing apoptotic cell death. We have also established that this sensitization is reliant on the farnesol response generated by QC. Molecular docking studies also support this conclusion and suggest that QC can form hydrogen bonds with Gln969, Thr1105, Ser1108, Arg1109, Asn1110, and Gly1061 in the ATP binding pocket of adenylate cyclase. Thus, this QS-mediated combined sensitizer (QC)-anticandidal agent (FCZ) strategy may be a novel way to enhance the efficacy of FCZ-based therapy of C. albicans infections. PMID:25645848

  2. Quercetin inhibits angiogenesis by targeting calcineurin in the xenograft model of human breast cancer.

    PubMed

    Zhao, Xin; Wang, Qiuting; Yang, Shijun; Chen, Chen; Li, Xiaoya; Liu, Jinyu; Zou, Zhongmei; Cai, Dayong

    2016-06-15

    Vascular endothelial growth factor receptor 2 (VEGFR2) mediated calcineurin/nuclear factor of activated T-cells (NFAT) pathway is crucial in the angiogenesis of human breast cancer. Quercetin (Qu), a flavonoid known to possess anti-angiogenesis and antitumor properties, inhibited calcineurin activity in vitro. Herein, we performed a study in vivo to evaluate the effects of Qu on the angiogenesis in breast cancer. Female BALB/c nude mice were injected with MCF-7 cells into the mammary fat and were randomly divided into four groups. The animals were treated with vehicle solution, tamoxifen (TAM, 5.6mg/kg), tacrolimus (FK506, 3mg/kg), or Qu (34mg/kg) for 21 days, respectively. The results showed that, similar to TAM and FK506, Qu decreased tumor growth, limited oncocyte proliferation and promoted tumor necrosis. Anti-angiogenic actions of Qu were demonstrated as decreased serum VEGF (P<0.01), and sparse microvessel density (P<0.05). Qu significantly inhibited tumor calcineurin activities, and the inhibitory rate was 62.73% in Qu treated animals, compared to that was 72.90% in FK506 group (P>0.05). Effects of Qu on calcineurin/NFAT pathway were confirmed as decreased subcellular located levels of VEGF (P<0.05), VEGFR2 (P<0.05) and NFATc3 (P<0.01), downregulated gene expression of VEGF (P<0.05), VEGFR2 (P<0.05) and NFATc3 (P<0.01), reduced protein levels of VEGF (P<0.05), VEGFR2 (P<0.05), and NFATc3 (P<0.01) in tumor tissues. These findings indicate that Qu inhibit angiogenesis of human breast cancer xenograft in nude mice, which was associated with suppressing calcineurin activity and its regulated pathway activation. PMID:27041643

  3. Effect of Antioxidant Flavonoids (Quercetin and Taxifolin) on In vitro Maturation of Porcine Oocytes.

    PubMed

    Kang, Jung-Taek; Moon, Joon Ho; Choi, Ji-Yei; Park, Sol Ji; Kim, Su Jin; Saadeldin, Islam M; Lee, Byeong Chun

    2016-03-01

    Quercetin (QT) and taxifolin (TF) are structurally similar plant-derived flavonoids that have antioxidant properties and act as free radical scavengers. The objective of this study was to investigate effects of QT and TF on nuclear maturation of porcine oocytes. Effects of TF at 0, 1, 10, and 50 μg/mL on oocyte nuclear maturation (polar body extrusion) were investigated. After incubation for 44 h, there were no significant differences between the treatment and control groups except in the 50 μg/mL group which was significantly lower (59.2%, p<0.05) than the other groups (control: >80%). After parthenogenetic activation, further in vitro development of QT- or TF-treated vs control oocytes was investigated. A significantly higher proportion of QT-treated (1 μg/mL) oocytes developed into blastocysts compared to controls (24.3% vs 16.8%, respectively); however, cleavage rate and blastocyst cell number were not affected. The TF-treated group was not significantly different from controls. Levels of reactive oxygen species (ROS) and intracellular glutathione (GSH) in oocytes and embryos in a culture medium supplemented with QT or TF were measured. Both treatment groups had significantly lower (p<0.05) levels of ROS than controls, however GSH levels were different only in QT-treated oocytes. We conclude that exogenous flavonoids such as QT and TF reduce ROS levels in oocytes. Although at high concentration (50 μg/mL) both QT and TF appear to be toxic to oocytes. PMID:26950865

  4. Synthesis of Quercetin Loaded Nanoparticles Based on Alginate for Pb(II) Adsorption in Aqueous Solution

    NASA Astrophysics Data System (ADS)

    Qi, Yun; Jiang, Meng; Cui, Yuan-Lu; Zhao, Lin; Zhou, Xia

    2015-10-01

    Pb(II) is a representative heavy metal in industrial wastewater, which may frequently cause serious hazard to living organisms. In this study, comparative studies between alginate nanoparticles (AN) and quercetin-decorated alginate nanoparticles (Q-AN) were investigated for Pb(II) ion adsorption. Characterization of AN and Q-AN were analysed by transmission electron microscopy (TEM), Fourier transform infrared spectrometry (FT-IR), X-ray diffractometer (XRD), and thermogravimetric analysis (TG-DTG-DSC). The main operating conditions such as pH, initial concentration of Pb(II), and co-existing metal ions were also investigated using a batch experiment. AN and Q-AN, with a diameter of 95.06 and 58.23 nm, were constituted by many small primary nanoparticles. It revealed that when initial concentration of Pb(II) is between 250 and 1250 mg L-1, the adsorption rate and equilibrium adsorption were increased with the increase of pH from 2 to 7. The maximum adsorption capacities of 147.02 and 140.37 mg L-1 were achieved by AN and Q-AN, respectively, with 0.2 g adsorbents in 1000 mg L-1 Pb(II) at pH 7. The adsorption rate of Pb(II) was little influenced by the co-existing metal ions, such as Mn(II), Co(II), and Cd(II). Desorption experiments showed that Q-AN possessed a higher desorption rate than AN, which were 90.07 and 83.26 %, respectively. AN and Q-AN would probably be applied as adsorbents to remove Pb(II) and then recover it from wastewater for the advantages of simple preparation, high adsorption capacity, and recyclability.

  5. Thermally Accelerated Oxidative Degradation of Quercetin Using Continuous Flow Kinetic Electrospray-Ion Trap-Time of Flight Mass Spectrometry