• Journal of Pharmaceutical Investigation
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• 제34권1호
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• pp.29-34
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• 2004

The solubility and stability of quercetin in various vehicles were determined. The solubility of quercetin at $28^{\circ}C$ increased in the rank order of isopropyl myristate < oleyl alcohol < propylene glycol monolaurate < oleoyl macrogol­6 glycerides < linoleoyl macrogol-6 glycerides < propylene glycol laurate (PGL) < propylene glycol monocaprylate (PGMC) < polyethylene glycol-8 glyceryl linoleate < caprylocaproyl macrogol-6 glycerides < diethylene glycol mono ethyl ether (DGME). The addition of DGME to non-aqueous vehicles such as PGL ad PGMC markedly increased the solubility of quercetin. From the stability studies, it was found that quercetin was unstable due to rapid oxidation by dissoved oxygen. The addition of a combination of ascorbic acid and edetic acid (EDTA) at 0.1 % markedly decreased the degradation rates of quercetin in 40% polyethylene glycol 400 in saline. Quercetin was relatively unstable in non-aqueous vehicles such as PGL and PGMC alone, and PGL-PGMC co-solvent The degradation of quercetin in such non-aqueous vehicles was fast, depending on temperature. The addition of butylated, hydroxytoluene, butylated hydroxyanisole, citric acid and/or EDTA at 0.1 % was effective in retarding the degradation of quercetin.

• Biomolecules & Therapeutics
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• 제24권2호
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• pp.191-198
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• 2016

The vitamin D receptor (VDR) is a member of the nuclear receptor (NR) superfamily. The VDR binds to active vitamin $D_3$ 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 ($K_d$) of quercetin and the VDR was $21.15{\pm}4.31{\mu}M$, 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.

• International Journal of Oral Biology
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• 제40권2호
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• pp.85-91
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• 2015

Quercetin is a natural flavonoid phytochemical that is extracted from various plants. Having an advantages due to its varied biological properties, such as anti-inflammatory, anti-viral, anti-oxidant, and anti-cancer effects, quercetin is used to treat many diseases. Recently, it has been reported that autophagy inhibition may play a key role in anti-cancer therapy. Therefore, in this study, we investigated the molecular mechanisms and anti-cancer effects of quercetin in human osteosarcoma cells via autophagy inhibition. We ascertained that quercetin inhibited cell proliferation and induced cell death, these process is demonstrated that apoptosis via the mitochondrial pathway and the caspase cascade. Quercetin also induced autophagy which was inhibited by 3-MA, autophagy inhibitor and the blockade of autophagy promoted the quercetin-induced apoptosis, confirming that autophagy is a pro-survival process. Thus, these findings demonstrate that quercetin is an effective anti-cancer agent, and the combination of quercetin and an autophagy inhibitor should enhance the effect of anti-cancer therapy.

• 생명과학회지
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• 제32권11호
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• pp.899-907
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• 2022

Quercetin은 과일과 채소에 풍부한 플라보노이드 중의 하나로써, 항산화, 항염증, 항암, 항바이러스 활성 등 다양한 약리학적 활성을 가지고 있는 것으로 알려져 있다. 본 연구에서는 in vitro 모델에서 quercetin의 항염증 활성과 작용기전을 연구하였다. Quercetin은 LPS로 자극된 RAW264.7에서 세포 생존율에 영향 없이 NO 생산을 농도 의존적으로 저해하였고, iNOS와 COX-2 단백질의 발현을 억제하였다. 게다가, quercetin은 LPS로 유도된 p38, JNK, ERK의 인산화를 농도 의존적으로 저해하였고, NF-κB p65 단백질과 억제자인 IκBα 단백질의 인산화를 저해하였다. 이러한 결과는 quercetin의 항염증 활성이 MAPK 경로와 NF-κB를 조절함으로써 이루어진다는 것을 시사한다. Quercetin에 의해 4종류의 친 염증성 cytokine (CSF2, IL-1β, IL-6, TNF-α)의 발현 변화를 정량적 real-time PCR 방법으로 확인한 결과, 모든 cytokine 유전자의 발현이 감소됨을 확인하였다. 종합적으로, 본 연구결과는 플라보노이드 quercetin이 RAW264.7 세포에서 LPS로 유도된 염증반응을 MAPK 경로와 NF-κB경로를 통해 억제하고 친염증성 cytokine 유전자의 발현을 억제함으 로써 조절한다는 것을 제시한다.

• 약학회지
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• 제46권1호
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• pp.75-80
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• 2002

Quercetin is one of the bioflavonoid compounds and has multiple biological effects such as antioxidant and effective anti-inflammatory agent. Melanin has an important role in protecting human skin from the damaging effects of ultra-violet W) radiation. We studied the effect of quercetin on proliferation of B16/F10 melanoma cells. After 48h treatment of cells with quercetin, the cells exhibited a dose-dependent inhibition in their proliferation without apoptosis. Therefore, the decrease in cell numbers may be due to cell growth arrest, not due to cell death by cytotoxicity. We also investigated the effect of quercetin on melanogenesis of this cells. B16/F10 melanoma cells were grown for 48h in the presence of 0.01~50$\mu\textrm{g}$/ml quercetin and the total melanin contents were measured. Quercetin stimulated melanization of the cells in low concentrations (0.01~20$\mu\textrm{g}$/ml), whereas it inhibited melanization in high concentrations (30~50$\mu\textrm{g}$/ml). It was observed that quercetin differently regulates melanogenesis of B16/F10 melanoma cells dependent on its concentrations.

• Bulletin of the Korean Chemical Society
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• 제35권9호
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• pp.2787-2790
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• 2014

Quercetin is a major dietary flavonoid found in onions, apples, tea, and red wine, and potentially has beneficial effects on disease prevention. We carried out this study to investigate the effect of quercetin on UVB-induced matrix metalloproteinase-1 (MMP-1) expression in human keratinocyte HaCaT cells and to further understand the mechanisms of its action. The anti-inflammatory activity of quercetin was investigated and quercetin significantly suppressed the NO production in LPS-stimulated RAW264.7 mouse macrophages. Post treatment of quercetin decreased UV irradiation-induced phosphorylation of JNK, p38 MAPK, and ERK by 91%, 21%, and 17%, respectively. MMP-1 is mainly responsible for the degradation of dermal collagen during the aging process of human skin and quercetin suppressed the UVB-induced MMP-1 by 94%. Binding studies revealed that quercetin binds to p38 with high binding affinity ($1.85{\times}10^6M^{-1}$). The binding model showed that the 4'-hydroxy groups of the B-ring of quercetin participated in hydrogen bonding interactions with the side chains of Lys53, Glu71, and Asp168 and the 5-hydroxy group of the A-ring formed a hydrogen bond with the backbone amide of Met109. The major finding of this study shows that quercetin inhibits phosphorylation of JNK, p38 MAPK, and ERK pathway leading to the prevention of MMP-1 expression in human keratinocyte HaCaT cells. Therefore, our findings suggested the potentials of quercetin as a skin anti-photoaging agent.

• 한국식품저장유통학회:학술대회논문집
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• 한국식품저장유통학회 2003년도 춘계총회 및 제22차 학술발표회
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• pp.106-107
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• 2003

양파는 세계적으로 가장 많이 사용하는 약용식물이며 식품에도 많이 이용되어왔다. 기존의 많은 연구들은 양파에는 많은 양의 quercetin이 함유되어 있다고 보고하였으며, quercetin은 주로 와인, 차, 양파, 사과와 같은 식품이나 과일이나 채소에 존재한다고 알려져 왔다. 그러나 과거에는 quercetin은 돌연변이성이 있으며, 종양의 크기를 증가시키는 원인으로 알려져 왔으나 최근에는 quercetin은 식품으로 섭취하였을 때, antithrombotic, antiallergic, antiviral과 antiinflammatory 효과를 갖는다고 보고되었다. 최근에는 자연적인 항암제로써 잠재성을 갖고 있다고 보고하고 있다. 이번 연구에서 onion을 4부위 (skin, outward, middle, core)로 분리 후 각각의 부위별 quercetin의 함량을 비교분석 하였다. 각각의 부위는 동결건조 후 HPLC를 사용하여 374 nm에서 $C_{18}$ coloum을 가지고 분석하였다. 그 결과 각각부위별 quercetin의 함량은 skin, outward, middle, core에서 8.41 mg/g, 1.34 mg/g, 0.47 mg/g, 0.18 mg/g로 측정되었다. 결국 중심에서 밖으로 갈수록 quercetin의 함량이 증가하는 것이 판명되었으며 특히, skin에서 quercetin의 함량은 가식부위와 비교하였을 때 가장 높은 것으로 나타났다.

• The Korean Journal of Physiology and Pharmacology
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• 제21권2호
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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.

• 약학회지
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• 제42권4호
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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.

• Molecules and Cells
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• 제38권7호
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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.