• The Korean Journal of Physiology and Pharmacology
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• v.21 no.2
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• pp.205-213
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• 2017

Quercetin, a plant-derived flavonoid found in fruits, vegetables and tea, has been known to possess bioactive properties such as anti-oxidant, anti-inflammatory and anti-cancer. In this study, anti-cancer effect of quercetin and its underlying mechanisms in triple-negative breast cancer cells was investigated. MTT assay showed that quercetin reduced breast cancer cell viability in a time and dose dependent manner. For this, quercetin not only increased cell apoptosis but also inhibited cell cycle progression. Moreover, quercetin increased FasL mRNA expression and p51, p21 and GADD45 signaling activities. We also observed that quercetin induced protein level, transcriptional activity and nuclear translocation of Foxo3a. Knockdown of Foxo3a caused significant reduction in the effect of quercetin on cell apoptosis and cell cycle arrest. In addition, treatment of JNK inhibitor (SP 600125) abolished quercetin-stimulated Foxo3a activity, suggesting JNK as a possible upstream signaling in regulation of Foxo3a activity. Knockdown of Foxo3a and inhibition of JNK activity reduced the signaling activities of p53, p21 and GADD45, triggered by quercetin. Taken together, our study suggests that quercetin induces apoptosis and cell cycle arrest via modification of Foxo3a signaling in triple-negative breast cancer cells.

• Microbiology and Biotechnology Letters
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• v.34 no.4
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• pp.368-372
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• 2006

Quercetin is a flavonoid molecule that is known to tie in various sources of natural products such as vegetables and fruits. It has been proven that quercetin plays a crucial role in the prevention of colon cancer as well as homeostasis as radical scavenger in human body. It is also well-known that glycosidases, including $\alpha$-glucosidase, are involved in a variety of degenerative metabolic disorders. In the course of screening useful $\alpha$-glucosidase inhibitors, we screened out quercetin as a $\alpha$-glucosidase inhibitor from chemical libraries. Quercetin was shown to be a reversible, slow-binding, and noncompetitive inhibitor of yeast a-glucosidase with a K$_i$ value of $6.3\times10^{-8}$ M when it was included with an enzyme mixture. Together, these results show that quercetin has potential in treating disorders including diabetes, although the further mechanistic study is needed.

• Molecules and Cells
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• v.38 no.7
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• pp.638-642
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• 2015

Quercetin can suppress osteosarcoma cell growth and metastasis. However, other effects of quercetin on osteosarcoma remain largely unknown. This research aims to evaluate the effects of quercetin in combination with cisplatin as treatment for osteosarcoma and investigate its regulatory mechanism. Cell viability and apoptosis in 143B cell line were determined after treatment with quercetin and/or cisplatin. RT-PCR and Western blot analysis were performed to determine the RNA or protein expression levels. Moreover, transwell assay was used to evaluate metastasis. Furthermore, rescue experiments were performed to investigate the potential regulatory mechanism of the treatment. Results showed that quercetin with concentration that was equal to or greater than $10{\mu}M$ inhibited 143B proliferation, while $5{\mu}M$ quercetin enhanced the cisplatin sensitivity of 143B cells. Expression of miR-217 was upregulated after quercetin and/or cisplatin treatment, while its target KRAS was downregulated both at mRNA and protein levels. MiR-217 knockdown led to the loss of enhanced cisplatin sensitivity while miR-217 overexpression showed the opposite effects, indicating that quercetin regulated cisplatin sensitivity by modulating the miR-217-KRAS axis. In conclusion, $5{\mu}M$ quercetin enhanced the cisplatin sensitivity by modulating the miR-217-KRAS axis. This finding suggests that quercetin may be administered with cisplatin to improve the treatment for osteosarcoma.

• The Korean Journal of Physiology and Pharmacology
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• v.13 no.5
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• pp.361-365
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• 2009

Effects of quercetin, a kind of flavonoids, on the vasodilating actions were investigated. Among the mechanisms for quercetin-induced vasodilatation in rat aorta, the involvement with the $Ca^{2+}$ activated $K^+$ ($K_{Ca}$) channel was examined. Pretreatment with NE ($5\;{\mu}M$) or KCl (60 mM) was carried out and then, the modulation by quercetin of the constriction was examined using rat aorta ring strips (3 mm) at $36.5^{\circ}C$. Quercetin (0.1 to $100\;{\mu}M$) relaxed the NE-induced vasoconstrictions in a concentrationdependent manner. NO synthesis (NOS) inhibitor, NG-monomethyl-L-arginine acetate (L-NMMA), at $100\;{\mu}M$ reduced the quercetin ($100\;{\mu}M$)-induced vasodilatation from $97.8{\pm}3.7%$ (n=10) to $78.0{\pm}11.6%$ (n=5, p<0.05). Another NOS inhibitor, L-NG-nitro arginine methyl ester (L-NAME), at $10\;{\mu}M$ also had the similar effect. In the presence of both $100\;{\mu}M$ L-NMMA and $10\;{\mu}M$ indomethacin, the quercetin-induced vasodilatation was further attenuated by $100\;{\mu}M$ tetraethylammonium (TEA, a $K_{Ca}$ channel inhibitor). Also TEA decreased the quercetin-induced vasodilatation in endothelium-denuded rat aorta. Used other $K_{Ca}$ channel inhibitors, the quercetin-induced vasodilatation was attenuated by $0.3\;{\mu}M$ apamin (a SK channel inhibitor), but not by 30 nM charybdotoxin (a BK and IK channel inhibitor). Quercetin caused a concentration-dependent vasodilatation, due to the endotheliumdependent and -independent actions. Also quercetin contributes to the vasodilatation selectively with SK channel on smooth muscle.

• YAKHAK HOEJI
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• v.42 no.4
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• pp.414-421
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• 1998

In order to compare the suppressive effect of quercetin and its glycosides, such as quercitrin (quercetin-3-rhamnoside), isoquercitrin (quercetin-3-glucoside), hyperin (querceti n-3-galactoside)and rutin (quercetin-3-rhamnosyl glucoside), on the genotocicity by benzo(a)pyrene(B(a)P), in vitro sister chromatid exchange(SCE) test using mouse spleen lymphocytes and in vivo micronucleus test using mouse peripheral blood were performed. B(a)P-induced SCEs in vitro were slightly decreased by the simultaneous treatment of quercetin and its glycosides, although there was no significant decrease. On the other hand, MNU induced micronucleated reticulocytes(MNRL7s) in vivo were significantly decreased with a dose-dependent manner in all compounds tested. However, there were no differences between quercetin aglycone and glycosides in the suppressive effects under experimental condition of this study. To elucidate, the action mechanism of quercetin aglycone and its glycosides against B(a)P-induced genotoxicity, the assay of DNA binding with B(a)P was studied. Quercetin aglycone and its glycosides inhibited B(a)P metabolism in the presence of S-9 mix and decreased the B(a)P/DNA binding in the calf thymus DNA with S-9 mix. These results suggest that antigenotoxicity of quercetin antiglycosides on B(a)P-induced genotoxicity is due to decrease of DNA binding with B(a)P through the inhibition of metabolism with B(a)P in the calf thymus DNA. Therefore, quercetin and its glycosides may act as an antigenotoxicity agent and may be useful as a chemopreventive agent of polycyclic aromaic hydrocarbons like B(a)P.

• Journal of Pharmaceutical Investigation
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• v.34 no.4
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• pp.283-288
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• 2004

The pharmacokinetics of nifedipine was studied after oral coadministration of nifedipine (5 mg/kg) with quercetin (1.5, 7.5, 15 and 30 mg/kg, respectively) and 0.5 h or 3days pretreatment with quercetin (1.5 and 7.5mg/kg) in rabbits. Pretreatment of quercetin significantly (p<0.05, at 0.5 h; p<0.01, at 3 days) increased the plasma concentration of nifedipine, but not significant in coadministraiton. The area under the plasma concentration-time curve (AUC) and the peak concentration $(C_{max})$ of nifedipine pretreated with quercetin were increased significantly (p<0.05, at 0.5 h; p<0.01, at 3 days) compared to the control. By coadministration of quercetin, only 7.5 mg/kg of quercetin increased plasma AUC and $C_{max}$ of nifedipine significantly (p<0.05) compared to the control. Plasma AUC of intravenous nifedipine (1 mg/kg) is $4235\;{\pm}\;1192\;ng/ml{\cdot}hr$. Pretreatment of quercetin significantly (p<0.05, at 0.5 h; p<0.01, at 3 days) increased the absolute bioavailability (AB%) of nifedipine to 23.9-29.2% compared to the control (17.8%). Coadministration of quercetin showed no significant effect on the AB% of nifedipine except for 7.5 mg/kg. It is suggested that quercetin alters disposition of nifedipine by inhibition of P-glycoprotein efflux pump and its first-pass metabolism. The dosage of nifedipine should be adjusted when it is administered chronically with quercetin in a clinical situation.

• Food Engineering Progress
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• v.13 no.2
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• pp.147-153
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• 2009

Quercetin is one of the main flavonoids from onion. To use quercetin as a functional component for onion food products, the effects of various extraction assisting methods such as juicing methods, microwave, ultrasound and enzyme treatments on the yield of quercetin and its glucosides were investigated. For conventional solvent extraction, the highest yield of quercetin and its glycosides was achieved with 0.8 mL/g of 60% methanol at 50$^{\circ}C$ for 15 min. The juicing methods using mixer and screw showed no influence on the yield. Microwave and ultrasound treatments showed 2.14 times and 2.06 times more quercetin yields than non-treated extraction, respectively. For cellulase and viscozyme treatments, the highest yields of quercetin were achieved with 0.5 mL/g of 1% enzyme-0.1M sodium acetate (pH 5.2) buffer solution. Cellulase and viscozyme treatment improved quercetin yield 1.65 times and 2.29 times more than non-treated one, respectively.

• Asian-Australasian Journal of Animal Sciences
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• v.23 no.6
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• pp.742-749
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• 2010

We investigated the antioxidant efficacy of quercetin (0% Diet 1, 0.25% Diet 2, and 0.5% Diet 3) pretreatment for 30 and 60 days in response to cadmium (Cd) toxicity in the olive flounder, and measured the plasma lysozyme activity to understand the immune effects of quercetin. The lysozyme activity with Diets 2 and 3 was higher than with Diet 1. Based on this result, to examine the immune ability and antioxidant role of quercetin, we exposed olive flounder fed quercetin to Cd and then measured the expression and activity of antioxidant enzymes (superoxide dismutase (SOD) and catalase (CAT)) and lipid peroxidation (LPO). With Diets 2 and 3, the expression and activity of antioxidant enzymes and the $H_2O_2$ concentration were lower than with Diet 1. In addition, the LPO levels were lower than with Diet 1, which protected the cell membrane. Therefore, quercetin removed the reactive oxygen species (ROS) produced by Cd, indicating that quercetin has antioxidant ability. In addition to its antioxidant ability, quercetin has immune effects.

• Nutrition Research and Practice
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• v.6 no.4
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• pp.301-307
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• 2012

Radiation used in cancer treatment may cause side effects such as inflammation. Quercetin is a polyphenol that reduces inflammation. This study evaluated the recovery efficacy of quercetin on impaired immune function in irradiation-induced inflammatory mice. Quercetin administered at two concentrations of 10 and 40 mg/kg body weight was initiated 2 weeks before irradiation and was continued 30 days after irradiation. The animals exposed/not exposed to radiation were sacrificed on radiation days 10 and 30. Splenocyte proliferation, which was diminished after irradiation, was enhanced significantly by quercetin supplementation after 30 days of irradiation. Cytokine secretion increased in the radiation group compared to that in the non-radiation control group. After 30 days of radiation, interleukin (IL)-$1{\beta}$ and IL-6 secretion decreased significantly in the radiation-quercetin groups. When quercetin was administered for 44 days, it showed a possible protective effect against irradiation-induced inflammation in mice. Quercetin could be beneficial in the recovery of irradiation-induced increases in cytokine secretion.

• Journal of Embryo Transfer
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• v.29 no.2
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• pp.141-148
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• 2014

Quercetin and genistein, plentifully present in fruits and vegetables, are flavonoid family members that have antioxidative function and plant-derived phytoestrogen activity. The antioxidative effects of quercetin and genistein on boar sperm characteristics and in vitro development of IVF embryo were investigated. The sperm motility was increased by addition of genistein $50{\mu}M$ for 6 hr incubation compared to control (p<0.05). The sperm viability was increased by addition of quercetin 1 and $50{\mu}M$ and genestein 1 and $50{\mu}M$ for 3 hr incubation. In addition, the sperm viability seemed to be increased dose-dependantly by addition of quercetin or genistein 1 and $50{\mu}M$, respectively (p<0.05). The membrane integrities were not increased by quercetin or genistein treatments for 3 hr or 6 hr incubation period except for quercetin $1{\mu}M$ for 3 hr incubation. In mitochondrial activities, addition of quercetin $50{\mu}M$ for 6 hr incubation increased mitochondrial activity but decreased at $100{\mu}M$ concentration compared with control (p<0.05). When porcine IVF embryos were cultured in PZM-3 medium supplemented with low concentrations of quercetin ($1{\sim}10{\mu}M$), the developmental rates to morula and blastocyst increased but significantly decreased at high concentrations of quercetin ($25{\sim}50{\mu}M$). The highest developmental rate to blastocysts among all concentrations of quercetin was shown at quercetin $10{\mu}M$ (p<0.05). The developmental rates to morula or blastocysts at low ($0.01{\sim}1{\mu}M$) and high ($5{\sim}10{\mu}M$) concentrations of genistein were not significantly different among all treatment group and genistein did not affect on IVF embryo development. These results suggest that quercetin and genistein seem to have positive effects at certain concentrations on sperm characteristics such as motility, viability and mitochondrial activity. In addition, low concentrations of quercetin (1, 5 and $10{\mu}M$) in this experiment, seem to have beneficial effect on porcine IVF embryo development but genistein did not affect on it at all given concentrations ($0.01{\sim}10{\mu}M$).