甘草及其活性成分抗炎与抗炎机制的研究进展

甘草及其活性成分能提高吞噬细胞的吞噬功能、调节淋巴细胞数量与功能、抑制IgE抗体形成、抗炎症介质及前炎性细胞因子,具有抗炎、抗变态反应的药理活性.甘草黄酮类化合物(异甘草素、异甘草苷、甘草素、甘草查耳酮A、光甘草定、甘草醇等)、甘草多糖和甘草酸是其抗炎、抗变应性炎症的活性成分.其中对异甘草素、甘草查耳酮A和甘草酸的抗炎...     

甘草及其黄酮类化合物的神经保护作用

甘草及其黄酮类化合物对神经元有保护作用,能对抗缺血再灌注引起的脑损伤,也有改善学习记忆和抗抑郁作用。综述甘草粗提物及其异甘草素、甘草素、甘草查耳酮、光甘草定等黄酮类化合物的神经保护作用的研究进展文献,认为甘草及其黄酮类化合物的神经保护作用是其抗炎、抗氧化、抗细胞凋亡及抗胆碱酯酶、单胺氧化酶、环磷酸腺苷磷酸二酯酶等基本药理作用综合的结果。     

异甘草素的制备方法和药理作用研究进展

摘要：异甘草素是甘草中的黄酮类成分,属于羟基查耳酮类化合物。目前异甘草素主要从甘草中提取分离及人工合成方法制备。它具有较强的生物活性,如抗癌、抗艾滋病、抗糖尿病并发症等,因而成为富有研究开发潜力的化合物。笔者结合自己的部分研究结果,对异甘草素的制备方法和药理作用研究进展作简要介绍,并对异甘草素的研究开发前景进行探讨。     

异甘草素的制备方法和药理作用研究进展

异甘草素是甘草中的黄酮类成分,属于羟基查耳酮类化合物。目前异甘草素主要从甘草中提取分离及人工合成方法制备。它具有较强的生物活性,如抗癌、抗艾滋病、抗糖尿病并发症等,因而成为富有研究开发潜力的化合物。笔者结合自己的部分研究结果,对异甘草素的制备方法和药理作用研究进展作简要介绍,并对异甘草素的研究开发前景进行探讨。     

异甘草素抗肿瘤作用及其机制研究进展

异甘草素(ISL)是从甘草根茎中提取的生物活性成分之一。近年来,众多研究表明,ISL药理特性丰富,有抗癌、抗炎、抗氧化、抗过敏、抗心律失常、保肝、治疗艾滋病和免疫调节等作用,尤其抗肿瘤作用近年来成为研究的热点。本文就异甘草素常见抗肿瘤作用及可能的机制研究进展做出综述,为异甘草素进一步的研究和抗肿瘤新药的开发提供理论依据。     

UPLC-TOF-MS法鉴定胀果甘草药渣中黄酮类成分

目的建立胀果甘草药渣中黄酮类成分的超高效液相色谱-高分辨飞行时间质谱(UPLC-TOF-MS)定性分析方法。方法 AgilentSB-C18柱(100mm×4.6mm,1.8μm);流动相乙腈-0.1%甲酸水溶液,梯度洗脱;体积流量0.4mL/min;柱温25℃;检测波长254nm。ESI离子源,飞行时间质谱检测器。对比自制对照品进行鉴别。结果共鉴定出8个黄酮类成分,分别为2’,4,4’-三羟基查耳酮、甘草查耳酮D、甘草查耳酮甲、4’-羟基-2’’,2’’-二甲基吡喃[5’’,6’’,6,7]黄酮、甘草黄酮C、光甘草酮、甘草黄酮B和kanzonolE。结论建立了一种简单、可靠的UPLC-TOF-MS方法对胀果甘草药渣中黄酮类成分进行了鉴定,对胀果甘草药渣综合利用有一定参考价值。     

酸水解前后甘草中4个黄酮类化合物含量的变化

目的:建立甘草提取物中4个活性成分甘草苷、异甘草苷、甘草素和异甘草素的测定方法,并评价酸水解法对4个黄酮类化合物含量测定的影响。方法:采用高效液相色谱法,分别测定乌拉尔甘草乙醇提取液和酸水解提取液中4个活性成分的含量。色谱柱为Agilent HC-C18(150 mm×4.6 mm,5μm)柱,流动相为pH 3甲酸溶液-乙腈,梯度洗脱,流速0.8 mL.min-1,甘草苷和甘草素检测波长为276 nm,异甘草苷和异甘草素的检测波长为370 nm,柱温为25℃(室温)。结果:乌拉尔甘草乙醇提取液中甘草苷、异甘草苷、异甘草素占原药材的质量百分数分别为1.29%,0.33%,0.01%,因药材中甘草素含量过低,未检出;酸水解提取液中甘草苷、异甘草苷、甘草素、异甘草素占原药材的质量百分数分别为0.71%,0.32%,0.26%,0.11%。结论:酸水解法能显著提高甘草素和异甘草素的含量测定值。     

异甘草素抗肿瘤作用机制及其结构修饰研究进展

异甘草素抗肿瘤活性广泛,机制明朗,修饰物活性增强,具有抗肿瘤新药的开发潜力。本文综述了近年异甘草素的抗肿瘤作用机制及其结构修饰研究进展,总结出异甘草素7种抗肿瘤作用机制和3个方面的结构改造,为该类化合物的抗肿瘤新药研发奠定基础。     

异甘草素的研究进展

笔者查阅了异甘草素的国内外相关文献,从化学合成、提取分离技术、含量测定方法、药理作用等方面对其进行综述。结果异甘草素已被成功合成,有成熟的从植物中提取分离的技术,在抗肿瘤、抗氧化、解痉、保肝、抗心率失常等均具有广泛的药理作用,尤其是抑制癌细胞增生已有多篇文献报道,并有望开发成为一个具有抗肿瘤作用的黄酮类新药。     

单因素试验结合Box-Behnken设计-响应面法优化甘草中黄酮类成分的提取工艺

目的:优化甘草中黄酮类成分的提取工艺。方法:以芹糖甘草苷、甘草苷、芹糖异甘草苷、芒柄花苷4种黄酮类成分的总提取量为考察指标,以提取溶剂种类(水、乙醇)及其不同体积分数、加入量与提取时间为考察因素,在单因素试验基础上,运用Box-Behnken设计-响应面法优化甘草中黄酮类成分的提取工艺,并进行验证试验。结果:优化的提取工艺为以50%乙醇为提取溶剂,在0.200 g药材中加入50 mL,超声提取50 min。在验证试验中,芹糖甘草苷、甘草苷、芹糖异甘草苷、芒柄花苷提取量分别为10.733 0、27.784 9、3.441 9、0.429 1 mg/g(RSD均<3.0%,n=3),4种黄酮类成分平均总提取量为42.388 9 mg/g,与预测值(42.173 2mg/g)的相对误差为0.52%(n=3)。结论:优化的提取工艺简便、快捷、稳定,可用于甘草中黄酮类成分的提取。     

栽培甘草中黄酮类成分的研究

目的对栽培甘草的化学成分进行研究。方法溶剂法和色谱法分离化合物,光谱鉴定其结构。结果分离得到7个黄酮类化合物,分别为异甘草素(isoliquiritigentin)(Ⅰ),刺甘草查尔酮(echinatin)(Ⅱ),甘草查尔酮B(licochalconeB)(Ⅲ),甘草素(liquiritigenin)(Ⅳ),4′,7-二羟基黄酮(4′,7-dihydroxyflavone)(Ⅴ),甘草苷(liquiritin)(Ⅵ),异甘草苷(isoliquiritin)(Ⅶ)。结论7个化合物均为首次从栽培甘草中得到。     

国产甘草的质量评价

运用高效液相色谱法对国产15个产地的8种甘草中12个化合物,即甘草酸(glycyrrhizinic acid)、乌拉尔甘草皂甙甲(uralsaponin A)、乌拉尔甘草皂甙乙(uralsaponin B)、甘草甙(liquiritin)、异甘草甙(isoliquiritin).甘草素(liquiritigenin)、异甘草素(isoliquiritigenin)、甘草香豆素(glycycoumarin)、异甘草香豆素(isoglycycoumarin)、甘草查尔酮(licochalcone A)、甘草酚(glycyrol)和异甘草酚(isomycyrol),进行了分离和含量测定。根据测定的结果,对国产甘草的质量进行了综合评价。     

The antiviral and antimicrobial activities of licorice,a widely-used Chinese herb

Licorice is a common herb which has been used in traditional Chinese medicine for centuries. More than 20 triterpenoids and nearly 300 flavonoids have been isolated from licorice. Recent studies have shown that these metabolites possess many pharmacological activities, such as antiviral, antimicrobial, anti-inflammatory, antitumor and other activities. This paper provides a summary of the antiviral and antimicrobial activities of licorice. The active components and the possible mechanisms for these activities are summarized in detail. This review will be helpful for the further studies of licorice for its potential therapeutic effects as an antiviral or an antimicrobial agent.Abbreviations: CCEC, cerebral capillary vessel endothelial; CCL5, chemokine (C-C motif) ligand 5; CVA16, coxsackievirus A16; CVB3, coxsackievirus B3; CXCL10, chemokine, (C-X-C motif) ligand 10; DGC, dehydroglyasperin C; DHV, duck hepatitis virus; EV71, enterovirus 71; GA, 18β-glycyrrhetinic acid; GATS, glycyrrhizic acid trisodium salt; GL, glycyrrhizin; GLD, glabridin; HBV, hepatitis B virus; HCV, hepatitis C virus; HIV, human immunodeficiency virus; HMGB1, high-mobility-group box1; HRSV, human respiratory syncytial virus; HSV, herpes simplex virus; HSV1, herpes simplex virus type 1; IFN, interferon; IL-6, interleukin-6; LCA, licochalcone A; LCE, licochalcone E; ISL, isoliquiritigenin; LTG, liquiritigenin; MgIG, magnesium isoglycyrrhizinate; MRSA, methicillin-resistant Staphylococcus aureus; MSSA, methicillin-sensitive Staphylococcus aureus; PMN, polymorph nuclear; PrV, pseudorabies virus; TCM, traditional Chinese medicineKEY WORDS: Licorice, Antiviral, Antimicrobial, Glycyrrhizin, Glycyrrhetinic acid, Chalcone     

Guanylate cyclase activator YC-1 potentiates apoptotic effect of licochalcone A on human epithelial ovarian carcinoma cells via activation of death receptor and mitochondrial pathways

Natural phenol licorice compounds have been shown to induce apoptosis in cancer cells. 3-(5'-Hydroxymethyl-2'-furyl)-1-benzyl indazole (YC-1) may enhance the sensitivity of cancer cells to anticancer drugs. However, the combined effect of licochalcone A and YC-1 on cell death in ovarian cancer cells has not been studied. We assessed the combined effect of licochalcone A and YC-1 on apoptosis in human epithelial ovarian carcinoma cell lines in relation to the cell death process. In the OVCAR-3 and SK-OV-3 cell lines, licochalocone A induced a decrease in Bid, Bcl-2, Bcl-xL and survivin protein levels; an increase in Bax levels; loss of the mitochondrial transmembrane potential; cytochrome c release; activation of caspases (-8, -9 and -3); cleavage of PARP-1; and an increase in the tumor suppressor p53 levels. YC-1 enhanced licochalcone A-induced apoptosis-related protein activation, nuclear damage and cell death. These results suggest that YC-1 may potentiate the apoptotic effect of licochalcone A on ovarian carcinoma cell lines by increasing the activation of the caspase-8- and Bid-dependent pathway and the mitochondria-mediated apoptotic pathway, leading to caspase activation. The combination of licochalcone A and YC-1 may confer a benefit in the treatment of human epithelial ovarian adenocarcinoma.     

甘草提取物及有效成分抗代谢相关脂肪性肝病的药理作用及机制研究进展

甘草是最常用的药用植物,广泛应用于食品及制药行业。甘草的化学成分主要有三萜皂苷类、黄酮类和多糖类等,具有抗氧化、免疫调节、抗病毒及抗炎保肝等多种药理作用。现代研究发现甘草提取物及有效成分（甘草酸、甘草次酸、甘草查尔酮A、甘草总黄酮等）能通过调节糖脂代谢、减轻氧化应激、改变肠道菌群、保护肠道屏障等机制达到改善及治疗代谢相关脂肪性肝病（MAFLD）的目的。综述近年来甘草提取物及有效成分抗MAFLD的药理作用及机制研究进展,旨在为该类药物的临床合理应用及新药研发提供理论依据。     

Identification of Key Licorice Constituents Which Interact with Cytochrome P450: Evaluation by LC/MS/MS Cocktail Assay and Metabolic Profiling

Licorice has been shown to affect the activities of several cytochrome P450 enzymes. This study aims to identify the key constituents in licorice which may affect these activities. Bioactivity assay was combined with metabolic profiling to identify these compounds in several complex licorice extracts. Firstly, the inhibition potencies of 40 pure licorice compounds were tested using an liquid chromatography/tandem mass spectrometry cocktail method. Significant inhibitors of human P450 isozymes 1A2, 2C9, 2C19, 2D6, and 3A4 were then selected for examination of their structural features by molecular docking to determine their molecular interaction with several P450 isozymes. Based on the present in vitro inhibition findings, along with our previous in vivo metabolic studies and the prevalence of individual compounds in licorice extract, we identified several licorice constituents, viz., liquiritigenin, isoliquiritigenin, together with seven isoprenylated flavonoids and arylcoumarins, which could be key components responsible for the herb–drug interaction between cytochrome P450 and licorice. In addition, hydrophilic flavonoid glycosides and saponins may be converted into these P450 inhibitors in vivo. These studies represent a comprehensive examination of the potential effects of licorice components on the metabolic activities of P450 enzymes.     

CYP3A4 inhibitors isolated from Licorice

The extract of licorice (Glycyrrhiza uralensis FISHER, Leguminosae) showed CYP3A4 inhibitory activity with the IC50 value of 0.022 mg/ml. Bioassay-guided purification afforded nine compounds, 3-(p-hydroxyphenyl)propionic acid (1), isoliquiritigenin (2), (3R)-vestitol (3), licopyranocoumarin (4), 4-hydroxyguaiacol apioglucoside (5), liquiritin (6), liquiritigenin 7,4'-diglucoside (7), liquiritin apioside (8), and glucoliquiritin apioside (9). Among these compounds, 3, 7, and 5 showed potent CYP3A4 inhibitory activities with IC50 values of 3.6, 17, and 20 microM, respectively. Glycyrrhizin (10), a main constituent of licorice, however, was inactive for CYP3A4 inhibition.     

Isoliquiritigenin suppresses cocaine-induced extracellular dopamine release in rat brain through GABA(B) receptor

Glycyrrhizae radix (licorice) comprises a variety of flavonoids as major constituents including isoliquiritigenin, liquiritin, liquiritigenin, and glycyrrihizin. It has shown various biological activities such as anti-inflammatory, anti-carcinogenic and antihistamic. As very little is known in regard to drug addiction, we carried out a study on the effect of G. radix and its active component, isoliquiritigenin, on acute cocaine-induced extracellular dopamine release in moving rats. Male Sprague-Dawley rats were orally administered with methanolic extracts of G. radix or isoliquiritigenin 1 h prior to an injection of cocaine (20 mg/kg, intraperitoneal (i.p.)). Extracellular dopamine was measured by in vivo microdialysis. Extract of G. radix and isoliquiritigenin inhibited cocaine-induced extracellular dopamine level in the nucleus accumbens by dose-dependent manner. Inhibition of dopamine release by isoliquiritigenin resulted in attenuation of the expression of c-Fos, an immediately early gene induced by cocaine. Effect of isoliquiritigenin was completely prevented by a GABA(B) receptor antagonist. Thus, these results showed that G. radix and isoliquiritigenin inhibit cocaine-induced dopamine release by modulating GABA(B) receptor, suggesting that isoliquiritigenin might be effective in blocking the reinforcing effects of cocaine.