甘草中黄酮类化合物的网络药理学研究

目的:分析、预测甘草中黄酮类化合物的潜在药理作用及可能作用机制。方法:采用网络药理学方法,依据中药整合药理学计算平台(TCMSP)等数据库,以化合物的口服药物生物利用度(OB)>30%和类药性(DL)>0.18为标准,筛选甘草中的黄酮类化合物。采用药效团匹配与PharmMapper数据库预测其潜在的作用靶点,随后借助生物学信息注释数据库V 6.8(DAVID V 6.8)分析工具对获得的靶点蛋白进行京都基因与基因组数据库(KEGG)信号通路分析和基因本体(GO)生物过程富集分析(以P<0.05为标准判断相关),并运用Cytoscape 3.5.1软件构建甘草中黄酮类化合物-靶点蛋白-信号通路网络图。结果:共从甘草中筛选出了19个黄酮类化合物(如甘草苷、异甘草苷、甘草素等),涉及细胞视黄酸结合蛋白2、脑啡肽酶等78个靶点蛋白(共188次),以及胰岛素信号通路、磷脂酰肌醇3激酶-丝氨酸/苏氨酸激酶(PI3K-Akt)等40条信号通路(其中与癌症相关的通路8条、与内分泌系统相关的通路7条、与信号转导相关的通路6条、与传染病相关的通路5条、与代谢相关的通路3条等);所建黄酮类化合物-靶点蛋白-信号通路网络图显示,甘草中黄酮类化合物可通过多个靶点作用于不同的疾病代谢通路。结论:甘草中黄酮类化合物对癌症、内分泌系统、传染病、代谢系统等方面疾病可能具有治疗作用,且可能有潜在的抗帕金森症作用。     

黄酮类化合物对三阴性乳腺癌肿瘤微环境的改善

目的 研究黄酮类化合物对三阴性乳腺癌(TNBC)肿瘤微环境(TME)的改善作用。方法 查阅国内外相关文献并归纳总结,综述黄酮类化合物通过影响TME对TNBC产生的作用。结果 黄酮类化合物通过不同机制,使TNBC细胞与TME相互作用,阻滞细胞周期、抑制癌细胞侵袭、转移、新血管生成和诱导细胞凋亡。结论 黄酮类化合物在TME中具有不同的抗TNBC活性,将TME作为治疗靶点的进一步研究具有重要意义。     

黄酮类化合物对内皮细胞损伤的保护作用及机制研究进展

血管内皮损伤是动脉粥样硬化的始动因素。目前,西医治疗的效果不佳且存在较多不良反应。中药有效成分黄酮类化合物可通过减轻炎症反应、抑制氧化应激、改善凋亡及自噬等途径调控内皮细胞功能,在动脉粥样硬化防治方面具有多途径、多环节、多靶点等优势,极具开发潜能。该文对近年来黄酮类化合物改善内皮损伤作用及机制研究进行了综述,为推动血管内皮损伤新型候选药物的发现及黄酮类化合物的广泛应用提供参考及理论依据。     

10种黄酮类化合物对糖尿病致病机制中重要通路的抑制作用

目的:观察10种黄酮类化合物对糖尿病致病机制中4条重要通路的多靶点抑制作用,发挥中药多靶点、综合治疗的优势。方法:从正常大鼠脑组织中提取半纯化的蛋白激酶C(PKC)、肾脏组织中提取醛糖还原酶(AR)粗酶,Fenton试剂体外激发正常大鼠脑组织脂质过氧化生成丙二醛(MDA)及体外合成高级糖化终产物(AGEs),将上述酶或合成物与10种黄酮类化合物(终浓度为1 mg.mL-1)作用,观察黄酮类化合物对上述酶或合成物的抑制作用。结果:黄芩苷和灯盏花素对AR,PKC,AGEs及MDA均有不同程度的抑制作用。结论:上述结果提示此两种黄酮类化合物可以通过抑制上述4条通路来预防糖尿病及其并发症的发生,为进一步的机制研究及临床应用提供良好的实验依据。     

分子对接技术筛选黑沙蒿中黄酮类化合物的PPAR-γ激动活性成分

目的:从黑沙蒿所含黄酮类化合物中筛选过氧化物酶体增殖物激活受体γ(PPAR-γ)的激动活性成分,为发现黑沙蒿中抗糖尿病药效物质提供参考。方法:以已知PPAR-γ激动药罗格列酮为阳性对照,采用分子对接技术对黑沙蒿中已分离得到的18个黄酮类化合物与PPAR-γ靶点进行一一分子对接,并对化合物与PPAR-γ靶点的对接亲和力、对接构象等进行分析比较,筛选黑沙蒿中可能的PPAR-γ激动活性成分。结果:有5个黄酮类化合物呈现了较好的对接亲和力,其中以化合物3(5,3′,4′-三羟基-7-甲氧基黄酮)亲和力最高(-8.3 kcal/mol);对接构象分析发现,黄酮类化合物A环与B环上的氧原子易与PPAR-γ配体结合域活性位点形成1个(Tyr327)或2个(Tyr327、Arg288)氢键结合,这对于黄酮类化合物与PPAR-γ的结合以及PPAR-γ构象的稳定起着重要作用。结论:采用分子对接技术进行的虚拟筛选结果表明,黑沙蒿中的黄酮类化合物(大多含有多个自由酚羟基)易与PPAR-γ形成较好的对接模式与较高亲和力,具有潜在抗糖尿病活性;本研究可为黑沙蒿治疗2型糖尿病的化学成分研究提供参考。     

黄酮类化合物对钙调素的拮抗作用

目的研究黄酮类化合物对钙调素的拮抗作用。方法用化学实验证实并比较三种黄酮类化合物杨酶素、槲皮素、蛇葡萄素对钙调素的拮抗作用。结果三种黄酮类化合物皆对CaM-PDE激活系统有拮抗作用。结论表明三种黄酮类化合物可通过抑制钙调素而影响PDE。从以上实验表明三种黄酮类化合物皆为特异的钙调素拮抗剂。     

黄酮类化合物防治良性前列腺增生的作用机制研究进展

黄酮类化合物是一类母核为苯并吡喃酮的多酚化合物的总称,具有抗氧化、抗炎、抗肿瘤、心脑血管保护等多种生物活性。近年来研究显示,黄酮类化合物在防治良性前列腺增生中具有一定的作用。综述了黄酮类化合物防治良性前列腺增生作用机制的研究进展。     

中药黄酮类化合物药理作用及作用机制研究进展

目的对黄酮类化合物的药理作用及其作用机制进行综述和分析。方法对近年来有关黄酮类化合物的药理作用及其作用机制的文献进行总结与分析。结果黄酮类化合物具有抗氧化、抗炎、镇痛、调节免疫、抗衰老、降血脂、抗肿瘤等药理作用,其作用机制可能与其抗自由基或抗氧化有关。结论黄酮类化合物是许多中草药的有效成分,具有广泛的生物活性,其产生生物活性的作用机制有待于进一步深入的研究。     

基于UPLC-Q-TOF-MS/MS和分子网络技术快速鉴定芦笋茎皮中的化学成分

本研究采用超高效液相-四级杆-飞行时间高分辨质谱联用(UPLC-Q-TOF-MS/MS)结合分子网络技术快速分析鉴定两种芦笋茎皮中的化学成分。通过化合物精确分子量、MS/MS裂解规律和文献报道数据等信息对两种芦笋茎皮中的化学成分进行鉴定,并根据MS/MS碎片的相似性创建分子网络。两种芦笋茎皮共鉴定107个化合物,包括皂苷类化合物46个、黄酮类化合物13个,有机酸类、氨基酸类和糖类等其他类成分48个。两种芦笋茎皮成分种类差异明显,白笋茎皮中富含皂苷类成分,而绿笋茎皮中富含黄酮类成分。本研究运用液质联用结合分子网络技术对芦笋茎皮中的化学成分进行快速分析,利用HIT 2.0中草药成分靶点数据库结合文献报道确定了芦笋茎皮中10个皂苷和黄酮类成分对乳腺癌的45个作用靶点,为芦笋资源的开发利用奠定了理论基础。     

基于UHPLC-Q-Orbitrap HRMS结合网络药理学的野鸦椿化学成分识别及作用

目的：野鸦椿是一种被用于治疗普通感冒的中草药,但其有效成分和作用机制尚不明确。本研究旨在探讨野鸦椿的有效成分和作用。方法：应用UHPLC-Q-Orbitrap HRMS来鉴定野鸦椿中的化学成分,结合网络药理学分析,寻找野鸦椿治疗常见的感冒相关症状鼻塞、打喷嚏、咳嗽、喉咙痛、头痛和发烧的成分、靶点、通路,并通过分子对接验证。结果：分析并鉴定了野鸦椿中57种化学成分,包括黄酮类化合物20个、三萜类化合物21个、酚酸类化合物9个以及其他化合物7个。发现包括多个黄酮类化合物quercetin、apigenin、kaempferol-3-O-glucoside在内的10个成分以及包括TNF、JUN、IL1B、IL6、NFKBIA、MAPK14、FOS在内的靶点可能是野鸦椿治疗普通感冒的关键。同时发现野鸦椿可能通过作用于IL-17 signaling pathway、TNF signaling pathway、COVID-19、AGE-RAGE signaling pathway等信号通路发挥治疗作用。分子对接结果显示,野鸦椿中关键活性成分与核心靶点的结合潜能较好。结论：野鸦椿中的多种活性成分可能...     

紫草素及其衍生物抗肿瘤作用研究进展

紫草的主要有效成分紫草素及其衍生物已被证实具有良好的抗肿瘤作用,其抗肿瘤作用机制涉及多个靶点。本文在文献报道的基础上,对紫草素及其衍生物的抗肿瘤作用及其机制进行综述。重点阐述紫草素及其衍生物在诱导细胞凋亡、诱导细胞坏死、以基质金属蛋白酶为作用靶点、作用于蛋白酪氨酸激酶、抗肿瘤血管再生等方面的抗肿瘤作用及其机制。最后对紫草素类衍生物抗肿瘤活性的研究现状进行概述,并对以紫草素为先导的抗肿瘤药物研究加以展望。     

蛋白酪氨酸激酶抑制剂的研究进展

蛋白酪氨酸激酶（PTK）抑制剂是一类作用于细胞信号转导通路的分子靶向药物,针对特定靶点发挥抗肿瘤作用。目前已有十余种蛋白酪氨酸激酶抑制剂上市,且它们在多种实体瘤的治疗中显示出较好的疗效。该文对近年来蛋白酪氨酸激酶抑制剂的研究进展做简要综述。     

Identification of biological targets through the correlation between cell line chemosensitivity and protein expression pattern

Matching biological data sequences is one of the most interesting ways to discover new bioactive compounds. In particular, matching cell chemosensitivity with a protein expression profile can be a useful approach to predict the activity of compounds against definite biological targets. In this review, we discuss this correlation. First, we analyze case studies in which some known drugs, acting on known targets, show a good correlation between their antiproliferative activities and protein expression when a large panel of tumor cells is considered. Then, we highlight how the application of in silico methods based on the correlation between cell line chemosensitivity and gene/protein expression patterns might be a quick, cheap, and interesting approach to predict the biological activity of investigated molecules.     

Protein interaction domain mapping for the selection of validated targets and lead compounds in the anti-infectious area

Despite considerable progress in the analysis of microbial genomes, the number of validated targets suitable for the development of drugs acting on agents causing infectious diseases remains modest. The diversity of new chemical entities specific for such targets has almost not increased over the last years, while resistance to anti-infectious drugs has, in contrast, become a real threat in certain surroundings. New strategies are thus needed for selecting novel validated targets. We discuss here a combined approach which uses protein interaction mapping as the basic strategy to identify interacting domains which then serve to validate newly identified targets. The interactome of Helicobacter pylori is used as model to successively describe high-throughput protein interaction mapping, use of the H. pylori data to predict the interactome from other bacteria, analysis of interacting domains, and evaluation of the capacity of one such domain to block synthesis of flagella. The general applicability of this approach to target identification and validation, and to development of novel compounds is also discussed.     

Therapeutic targets: progress of their exploration and investigation of their characteristics

Modern drug discovery is primarily based on the search and subsequent testing of drug candidates acting on a preselected therapeutic target. Progress in genomics, protein structure, proteomics, and disease mechanisms has led to a growing interest in and effort for finding new targets and more effective exploration of existing targets. The number of reported targets of marketed and investigational drugs has significantly increased in the past 8 years. There are 1535 targets collected in the therapeutic target database compared with approximately 500 targets reported in a 1996 review. Knowledge of these targets is helpful for molecular dissection of the mechanism of action of drugs and for predicting features that guide new drug design and the search for new targets. This article summarizes the progress of target exploration and investigates the characteristics of the currently explored targets to analyze their sequence, structure, family representation, pathway association, tissue distribution, and genome location features for finding clues useful for searching for new targets. Possible "rules" to guide the search for druggable proteins and the feasibility of using a statistical learning method for predicting druggable proteins directly from their sequences are discussed.     

HDL elevation and lipid lowering therapy: current scenario and future perspectives

High density lipoprotein (HDL) has proven its role in reverse cholesterol transport and cellular cholesterol efflux thus acting as a protective factor against atherogenic cardiovascular diseases. The article focuses primarily on structure and function of genes influencing HDL metabolism. Various novel targets involve liver X receptor, retinoid X receptor, peroxisome proliferators activated receptor agonists and apoA-I mimetics. New molecules targeting these nuclear receptors are described. Phospholipid transfer protein and scavenger receptor B1 are also attractive targets in HDL metabolism. ATP-Binding Cassette transporter A1 and several lipases also play a crucial role in HDL metabolism and are very useful target for atherogenic dyslipidemia. Cholesteryl ester transfer protein inhibitors have shown great promise as possible drug candidates of future. Notably, JTT-705 (Japan Tobacco, Roche) is of great interest in spite of withdrawal of torcetrapib. Considering modest effect of currently available therapeutic options on HDL, these novel HDL elevating targets are doubtlessly the target for future atherosclerotic intervention.     

AMP-activated protein kinase and metabolic control

AMP-activated protein kinase AMP-activated protein kinase (AMPK AMPK ), a phylogenetically conserved serine/threonine protein kinase, is a major regulator of cellular and whole-body energy homeostasis that coordinates metabolic pathways in order to balance nutrient supply with energy demand. It is now recognized that pharmacological activation of AMPK improves blood glucose homeostasis, lipid profile, and blood pressure in insulin-resistant rodents. Indeed, AMPK activation mimics the beneficial effects of physical activity or those of calorie restriction calorie restriction by acting on multiple cellular targets. In addition, it is now demonstrated that AMPK is one of the probable (albeit indirect) targets of major antidiabetic drugs drugs including the biguanides (metformin metformin ) and thiazolidinedione thiazolidinedione s, as well as of insulin-sensitizing adipokines (e.g., adiponectin adiponectin ). Taken together, such findings highlight the logic underlying the concept of targeting the AMPK pathway for the treatment of metabolic syndrome and type 2 diabetes.     

Monthly Update: Oncologic,Endocrine & Metabolic: What's new about new tubulin/microtubules binding agents?

Pharmaceutical research on new anticancer drugs continues in two directions: a ‘prospective’ one involving the selection of compounds acting on ‘new’ biological targets; and a ‘conservative’ one involving the selection of chemotherapeutic agents acting on ‘validated’ targets. Clinical interest in paclitaxel (Taxol?) and docetaxel (Taxotere?) has led to a reactivation of research on agents that bind tubulin/microtubules. Several new antimitotic compounds were presented at the American Association for Cancer Research meeting in Toronto, last April.     

泽泻汤治疗高血压药理机制的网络分析

目的： 利用网络药理学研究泽泻汤治疗高血压的作用机制。方法： 根据ADME计算方法,利用中药系统药理学技术平台（TCMSP）等数据库、反向分子对接服务器（DRAR-CPI）、人类基因组注释数据库（Gene Cards）预测和筛选泽泻汤的活性成分及其降血压作用靶点。借助Cytoscape 3.5.1软件构建泽泻汤活性成分-作用靶点网络,借助STRING平台构建靶蛋白互作网络,通过生物学信息注释数据库（DAVID）对靶点GO生物过程及KEGG信号通路进行分析。结果： 从泽泻汤中筛选出10个活性成分,作用于136个高血压相关靶点,涉及7个主要信号通路,参与10个主要生物过程。结论： 泽泻汤通过作用于醛固酮调节钠吸收、肾素血管紧张素（RAS）系统,NO信号转导等信号通路及生物过程发挥降压作用。