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蕺菜的药理学研究-槲皮素的抗炎作用

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现代药物与临床 1994年第2期9卷 75页

作者： Taguchi-K 刘湘译

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槲皮素抗肿瘤作用与Wnt/β-catenin信号转导关系的研究

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中华肿瘤防治杂志 2008年第21期15卷 1632-1635页

作者：李润青单保恩首都医科大学附属北京佑安医院临检中心北京100069 河北医科大学第四医院科研中心河北石家庄050011

目的:探讨槲皮素对人结肠癌细胞SW480增殖的影响及对细胞Wnt/β-catenin信号转导的调控作用。方法:以不同浓度的槲皮素处理SW480细胞,采用MTT比色法分析槲皮素对细胞增殖的抑制作用,利用报告基因方法研究槲皮素对Wnt/β-catenin信号转... 详细信息

目的:探讨槲皮素对人结肠癌细胞SW480增殖的影响及对细胞Wnt/β-catenin信号转导的调控作用。方法:以不同浓度的槲皮素处理SW480细胞,采用MTT比色法分析槲皮素对细胞增殖的抑制作用,利用报告基因方法研究槲皮素对Wnt/β-catenin信号转导的影响,用RT-PCR及蛋白质印迹法观察槲皮素对Wnt/β-catenin信号转导通路的下游关键因子Cyclin D1和Survivin转录水平和蛋白表达水平的影响。结果:(40～160)×10-6mol/L的槲皮素可明显抑制SW480细胞的增殖,P<0.01,抑制作用呈剂量依赖性和时间依赖性;(10～160)×10-6mol/L的槲皮素可明显抑制SW480细胞TCF-4报告基因TOPflash活性,P<0.05,抑制作用呈剂量依赖性。槲皮素可显著下调β-catenin/TCF下游靶基因CyclinD1和Survivin的mRNA表达和蛋白表达水平,呈剂量依赖性。结论:槲皮素可抑制人结肠癌细胞SW480的增殖,其抗肿瘤机制可能与其抑制Wnt/β-catenin信号转导通路有关。

关键词：结肠肿瘤/病理学槲皮素/药理学信号传导 cyclin D1 survivin

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槲皮素与芦丁对离体大鼠主动脉环的舒张作用及机制

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浙江大学学报（医学版） 2006年第1期35卷 29-33页

作者：周新妹姚慧夏满莉曹春梅蒋惠娣夏强嘉兴学院医学院生理学教研室浙江嘉兴314000 浙江大学医学院生理学教研室浙江杭州310031 浙江大学药学院浙江杭州310031

目的:比较研究槲皮素与芦丁对离体大鼠胸主动脉环的作用及其可能的途径。方法:采用累积加药法,检测槲皮素和芦丁对去氧肾上腺素(pheny lephrine,PE)预收缩的胸主动脉环张力的影响。结果:槲皮素对离体大鼠内皮完整和去内皮的胸主动脉环... 详细信息

目的:比较研究槲皮素与芦丁对离体大鼠胸主动脉环的作用及其可能的途径。方法:采用累积加药法,检测槲皮素和芦丁对去氧肾上腺素(pheny lephrine,PE)预收缩的胸主动脉环张力的影响。结果:槲皮素对离体大鼠内皮完整和去内皮的胸主动脉环均有浓度依赖性的舒张作用,而芦丁对PE预收缩血管的舒张作用是内皮依赖性的。槲皮素和芦丁对内皮完整的胸主动脉环的最大舒张反应分别为(77.20±6.11)%和(44.28±7.48)%,但两者对内皮完整的胸主动脉环最大舒张的半数有效浓度无明显差异。用一氧化氮合酶抑制剂L-NAM E(0.1 mm o l/L)预处理后,可阻断芦丁诱导的舒张血管作用,但不能阻断槲皮素引起的舒张血管作用;用鸟苷酸环化酶抑制剂亚甲蓝(10μm o l/L)预处理后,两者的血管舒张作用均被阻断。用环氧合酶抑制剂吲哚美辛(10μm o l/L)预处理后可减弱槲皮素诱导的舒张血管作用,但不能阻断芦丁引起的舒张血管作用。结论:槲皮素的舒血管作用强于芦丁,槲皮素可能是通过鸟苷酸环化酶和环氧合酶途径产生非内皮依赖性的血管舒张作用,而芦丁可能是通过NO-鸟苷酸环化酶途径产生内皮依赖性的血管舒张作用。

关键词：血管舒张药/药理学槲皮素/药理学芦丁/药理学主动脉,胸/药物作用内皮,血管

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Influence of phenolic compounds on the physiology of OEnococcus oeni from wine

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JOURNAL OF APPLIED MICROBIOLOGY 2000年第6期88卷 1065-1071页

作者： Reguant, C Bordons, A Arola, L Rozès, N Univ Rovira & Virgili CeRTA Unitat Enol Dept Bioquim & Biotecnol E-43005 Tarragona Catalonia Spain

This study shows that the growth of OEnococcus oeni CECT 4100 in a synthetic medium is affected by phenolic compounds in different ways, depending on their type and concentration. Generally they have no effects at low concentrations, but hydroxycinnamic acids are inhibitory at high concentrations. Malolactic fermentation was stimulated in the presence of catechin and quercetin, but increasingly delayed with increasing amounts of p-coumaric acid. Gallic acid appeared to delay or inhibit the formation of acetic acid from citric acid. This could lead to a better control of malolactic fermentation and suppress the increase in volatile acidity, which is undesirable in the wine-making process.

关键词：醋酸/分析儿茶素/药理学柠檬酸/分析柠檬酸/代谢香豆酸类/药理学乙醇食品工业食品微生物学没食子酸/药理学革兰氏阳性球菌/药物作用革兰氏阳性球菌/生长和发育革兰氏阳性球菌/代谢明串珠菌属/药物作用明串珠菌属/生长和发育明串珠菌属/代谢苹果酸盐/代谢丙酸盐类槲皮素/药理学葡萄酒/微生物学

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Artifacts in cell culture: Rapid generation of hydrogen peroxide on addition of (-)-epigallocatechin, (-)-epigallocatechin gallate, (+)-catechin, and quercetin to commonly used cell culture media

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BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 2000年第1期273卷 50-53页

作者： Long, LH Clement, MV Halliwell, B Natl Univ Singapore Fac Med Dept Biochem Singapore 119260 Singapore Natl Univ Singapore Fac Med Natl Univ Med Inst Clin Res CtrOncol Res Inst Singapore 117597 Singapore

There is considerable current interest in the possible beneficial health effects of quercetin, catechins, epigallocatechins, epigallocatechin gallates, and related phenolic compounds found in teas, wines, and other plant products. As a result, many laboratories are studying the effects of these compounds on cells in culture. The present paper shows that addition of these compounds to commonly used cell culture media leads to generation of substantial amounts of hydrogen peroxide (H2O2). Dulbecco's modified Eagle medium gives the highest H2O2 level for all the compounds tested, with levels reaching >400 mu M within 2 h for addition of 1 mM concentrations of gallic acid, epigallocatechin gallate, and epigallocatechin. Catechin and quercetin produced lower, but still significant, levels of H2O2. McCoy's 5A and RPMI 1640 media also promoted H2O2 production from the above phenolic compounds. This rapid generation of H2O2 could account for some or all of the reported effects of phenolic compounds on cells in culture. (C) 2000 Academic Press.

关键词：伪迹儿茶素/类似物和衍生物儿茶素/代谢儿茶素/药理学细胞培养技术/方法培养基/化学培养基/代谢剂量效应关系药物类黄酮物质/代谢类黄酮物质/药理学过氧化氢/分析过氧化氢/代谢槲皮素/代谢槲皮素/药理学时间因素

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Inhibition of human cytochrome P450 enzymes by constituents of St. John's wort, an herbal preparation used in the treatment of depression

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JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS 2000年第1期294卷 88-95页

作者： Obach, RS Pfizer Inc Div Cent Res Dept Drug Metab Candidate Synth Enhancement & Evaluat Groton CT 06340 USA

Commercially available St. John's wort (Hypericum perforatum) extracts, preparations that are used in the treatment of depression, were examined for the potential to inhibit human cytochrome P450 (CYP) enzyme activities, specifically CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Crude extracts demonstrated inhibition of each of these five enzymes, with CYP2D6, CYP2C9, and CYP3A4 being more sensitive than CYP1A2 and CYP2C19. Extracts were fractionated by HPLC, and each of the fractions was tested for inhibition of these five CYPs to identify individual constituents with inhibitory activity. Several fractions were shown to possess inhibitory activity, including the fractions containing hyperforin (the putative active antidepressant constituent), I3,II8-biapigenin, and hypericin. Hyperforin and I3,II8-biapigenin were isolated from the extract, and inhibition constants for the five CYP activities were measured. In addition, three other constituents, hypericin, quercetin, and chlorogenic acid, were tested for inhibitory activity toward the CYP enzymes. The flavonoid compound I3, II8-biapigenin was shown to be a potent, competitive inhibitor of CYP3A4, CYP2C9, and CYP1A2 activities with K-i values of 0.038, 0.32, and 0.95 mu M, respectively. Hyperforin was a potent noncompetitive inhibitor of CYP2D6 activity (K-i = 1.5 mu M) and competitive inhibitor of CYP2C9 and CYP3A4 activities (K-i = 1.8 and 0.48 mu M, respectively). Hypericin also demonstrated potent inhibition of several CYP activities. These in vitro data indicate that St. John's wort preparations contain constituents that can potently inhibit the activities of major human drug-metabolizing enzymes and suggest that these preparations should be examined for potential pharmacokinetic drug interactions in vivo.

关键词：抗抑郁药/药理学二环化合物绿原酸/药理学色谱法高压液相细胞色素P450酶系统/拮抗剂和抑制剂酶抑制剂/药理学金丝桃属二萘嵌苯/类似物和衍生物二萘嵌苯/药理学间苯三酚/类似物和衍生物植物提取物/药理学植物药用槲皮素/药理学萜类/药理学人类

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Quercetin inhibits benzo[a]pyrene-induced DNA adducts in human Hep G2 cells by altering cytochrome P-450 1A1 gene expression

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NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL 1999年第2期35卷 175-179页

作者： Kang, ZC Tsai, SJ Lee, H Chung Shan Med & Dent Coll Inst Toxicol Taichung Taiwan Natl Chung Hsing Univ Inst Food Sci Taichung 40227 Taiwan

Quercetin is one of the most abundant of the naturally occurring flavonoids. If has been estimated that about 25-50 mg of quercetin are consumed from the daily diet. The chemopreventive effect of quercetin on dietary carcinogen has been intensely studied in animal models;however, knowledge regarding the molecular mechanism is still limited. In this study, the human hepatoma Hep G2 cell line was used to investigate how quercetin prevents benzo[a]pyrene (B[a]P)-induced DNA adducts. The Hep G2 cells were treated with 10 mu M B[a]P for 18 hours in the presence or absence of quercetin. The DNA adduct levels, evaluated by P-32 postlabeling, decreased in a dose-dependent manner after treatment with quercetin. Cytochrome P-450 1A1 (CYP1A1) and glutathione S-transferase involvement have been well demonstrated in the modulation of B[a]P-induced DNA damage. From the assays of both enzyme activities, quercetin inhibits CYP1A1-linked ethoxyresorufin O-dealkylase activity more effectively than glutathione S-transferase activity. To elucidate the molecular mechanisms, reverse transcriptase-polymerase chain reaction and Western blot were used to evaluate whether the decrease in CYP1A1 enzyme activity by quercetin is mediated because of alterations of CYP1A1 transcription or mRNA stability. The results indicated that quercetin significantly inhibits B[a]P-induced CYP1A1 mRNA and protein expression. From these findings, we conclude that quercetin suppresses B[a]P-induced DNA damage in human Hep G2 cells by altering CYP1A1 gene expression. Thus we suggest that dietary quercetin may have a long-term preventive effect on chemical carcinogenesis, especially in people who eat a diet rich in fruits and vegetables.

关键词：抗致癌药/药理学放射自显影术苯并芘/投药和剂量苯并芘/药理学印迹法蛋白质癌肝细胞/代谢细胞色素P450CYP1A1/遗传学 DNA加合物/代谢 DNA损伤/药物作用剂量效应关系药物基因表达/药物作用肝肿瘤/代谢槲皮素/投药和剂量槲皮素/药理学逆转录聚合酶链反应肿瘤细胞培养的人类

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Inhibition of heat shock factor activity prevents heat shock potentiation of glucocorticoid receptor-mediated gene expression

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CELL STRESS & CHAPERONES 1999年第4期4卷 223-234页

作者： Li, DP Calzi, SL Sánchez, ER Med Coll Ohio Dept Pharmacol Toledo OH 43614 USA

Using mouse L929 cells stably transfected with a glucocorticoid receptor (GR)-responsive murine mammary tumor virus-chloramphenicol acetyltransferase (MMTV-CAT) reporter gene (LMCAT2 cells), we have shown that cellular stress (heat or chemical shock) can cause a dramatic increase in the levels of dexamethasone (Dex)-induced CAT gene expression. We refer to this response as the heat shock potentiation effect, or HSPE. As the cellular heat shock response also involves the activation of heat shock transcription factor (HSF), we have, in the present study, examined the role of HSF in the stress potentiation of GR by use of a flavonoid compound, quercetin, recently shown to selectively inhibit the stress response in a variety of human and murine cell lines. Analysis of the HSPE, as well as heat shock protein synthesis and activation of HSF during time-courses of recovery following heat shock, revealed a similar pattern for each response, with peak activities occurring about 16 h after stress. These data suggest a correlation between the activation of both GR and HSF in stressed cells. In L929 cells stably transfected with a CAT reporter plasmid under the control of the HSF-responsive hsp70 promoter (LHSECAT cells), pretreatment with quercetin was found to cause a dose- and time-dependent inactivation of HSF activity following heat shock, but only when added before the stress event. In LMCAT2 cells, quercetin similarly inhibited both heat and chemical shock potentiation of Dex-induced GR activity. This activity of quercetin was not the result of post-transcriptional or general cytotoxic properties, as quercetin (1) did not significantly affect GR or HSF activities when added after the stress event, (2) did not reduce CAT gene expression as controlled by the constitutive SV40 early promoter, and (3) did not alter normal (non-stress), Dex-induced MMTV-CAT expression. Thus, quercetin appears to be an effective and selective inhibitor of HSF stress-induced activation and its

关键词：亚砷酸盐类/药理学细胞系氯霉素O-乙酰转移酶 DNA结合蛋白质类/拮抗剂和抑制剂地塞米松/药理学剂量效应关系药物基因表达调控 HSP70热休克蛋白质类/代谢 HSP90热休克蛋白质类/代谢热休克蛋白质类/药物作用热休克蛋白质类/代谢模型生物学槲皮素/药理学受体糖皮质激素/药物作用受体糖皮质激素/代谢信号传导温度转录因子转染动物人类小鼠

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Compound 48/80 activates mast cell phospholipase D via heterotrimeric GTP-binding proteins

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JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS 2000年第1期292卷 122-130页

作者： Chahdi, A Fraundorfer, PF Beaven, MA NHLBI Lab Mol Immunol NIH Bethesda MD 20892 USA

Previous studies have indicated the presence of a cholera toxin-sensitive phospholipase D (PLD) in cultured RBL-2H3 mast cells that is synergistically activated via calcium, protein kinase C, and another unidentified signal. Here we identify a third potential signal for activation transduced by a pertussis toxin-sensitive trimeric GTP-binding protein, most likely via G(i2) or G(i3). Quercetin-treated RBL-2H3 cells in which expression of G(alpha i2) and G(alpha i3) is enhanced more than 7-fold respond to the G(i) stimulant compound 48/80 with the activation of PLD, a transient activation of phospholipase C, and enhanced membrane GTPase activity. The activation of PLD was blocked in pertussis toxin-treated cells and, as with other stimulants of PLD, was enhanced in cholera toxin-treated cells. The PLD response to compound 48/80 was only partially inhibited by calcium deprivation and inhibition of protein kinase C to indicate a component of the response that was independent of calcium, protein kinase C, and, presumably, phospholipase C. Based on these and other data, we hypothesized that beta gamma-subunits, released from G(i2) or G(i3) by compound 48/80 or from G(s) by cholera toxin, provide an additional signal for the activation of PLD. Consistent with this hypothesis, recombinant G(beta 2 gamma 2) subunits, but not G(alpha i-3) subunits, at concentrations of 50 to 300 nM markedly synergized PLD activation by compound 48/80 in permeabilized RBL-2H3 cells.

关键词：印迹法蛋白质钙/缺乏细胞膜/药物作用细胞膜/酶学细胞培养的霍乱毒素药物相互作用电泳 GTP磷酸水解酶类/代谢异源三聚体GTP结合蛋白质类/生理学肥大细胞/药物作用肥大细胞/代谢通透性百白咳毒素磷脂酶D/代谢蛋白激酶C/拮抗剂和抑制剂槲皮素/药理学信号传导时间因素毒力因子鲍特菌属 p-甲氧基-N-苯丙胺/药理学

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五昧子乙素诱导的HSP27和HSP70对ConA诱导小鼠肝损伤的保护作用

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第三军医大学学报 2013年第12期35卷 1210-1214页

作者：李丽波王玉祥杨宏艳辛亚兵高涵齐齐哈尔医学院药理学教研室黑龙江齐齐哈尔161006 齐齐哈尔医学院药学院黑龙江齐齐哈尔161006 齐齐哈尔医学院生物化学教研室黑龙江齐齐哈尔161006 齐齐哈尔市质量技术监督局食品科

目的:探讨五味子乙素(SchB)对刀豆蛋白A(ConcanavalinA,ConA)诱导小鼠肝损伤的保护作用与HSP27和HSP70的关系。方法:采用静脉注射ConA诱导小鼠免疫性肝损伤模型,SchB和热休克蛋白抑制剂槲皮素(Quercetin)灌胃给药。取4周龄雄性ICR小鼠72... 详细信息

目的:探讨五味子乙素(SchB)对刀豆蛋白A(ConcanavalinA,ConA)诱导小鼠肝损伤的保护作用与HSP27和HSP70的关系。方法:采用静脉注射ConA诱导小鼠免疫性肝损伤模型,SchB和热休克蛋白抑制剂槲皮素(Quercetin)灌胃给药。取4周龄雄性ICR小鼠72只,体质量18－22g,按体质量分为6组:正常对照组、模型组(ConA)、SchB+ConA组、SchB+ConA+Quercetin组、ConA+Quercetin组和Quercetin组。Westernblot法检测小鼠肝脏HSP27和HSPT0蛋白的表达;实时荧光定量PCR法检测小鼠肝脏HSP27和HSP70mRNA的表达;光镜下观察肝脏组织病理学改变;试剂盒检测小鼠血清转氨酶水平。结果:与ConA组相比,SchB+ConA组小鼠肝脏HSP27和HSP70在蛋白水平和mRNA水平的表达均显著增加,同时肝细胞坏死程度明显减轻、小鼠血清转氨酶水平显著降低。与SchB+ConA组相比,SchB+ConA+Quercetin组小鼠肝脏HSP27和HSPT0在蛋白水平和mRNA水平的表达均明显降低,同时小鼠肝细胞坏死程度明显增加、血清转氨酶水平显著增高。而与正常对照组相比,Quercetin组小鼠的上述各项指标未见改变。结论:SchB可通过诱导小鼠肝脏HSP27和HSP70的表达保护ConA所致的小鼠免疫性肝损伤。

关键词： HSC70热休克蛋白质类/代谢 RNA 信使/遗传学伴刀豆球蛋白A 肝/损伤腹部损伤/病理学腹部损伤/代谢热休克蛋白质类/代谢槲皮素/药理学五味子/化学疾病模型动物随机分配动物男(雄)性小鼠

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