中药治疗肺结核的用药规律及作用机制预测

目的 探索中药治疗肺结核的用药规律,并探讨高频药物的作用机制。方法 通过中国知网数据库和万方医学网检索中文文献,检索词为“肺结核”“中药”;通过PubMed数据库检索外文文献,检索词为“tuberculosis”“traditional Chinese medicine”;检索时间限定为1998年1月1日至2018年12月31日。共检索到相关文献512篇(中文文献405篇,英文文献107篇),最终纳入363篇(中文文献352篇,英文11文献篇)。运用Rapidminer软件进行信息提取,探索中医治疗肺结核的核心中药、常用配伍组合,分析用药规律及药物联用情况。采用BATMAN-TCM数据库获取高频药物的潜在活性成分及作用靶点,采用DisGeNET数据库、治疗靶点数据库(Therapeutic Target Database,TTD)及GeneCards数据库预测和筛选核心中药治疗肺结核的作用靶点,并对药物靶点和疾病靶点进行匹配。采用DAVID数据库对潜在靶点进行GO(Gene Ontology)生物功能及京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)分析。结果 中药治疗肺结核常用补虚药(663次),其次为活血化瘀药(403次)及清热药(325次),出现频次最多的药物为甘草(122次),其次为当归(102次)、生地(99次)、白芍(74次)。配伍组合频次最高的两两药对是甘草-当归(70次),其次为甘草-生地(52次);3味药组合出现频次最高的是甘草-当归-生地(37次),4味药组合出现频次最高的是甘草-当归-生地-白芍(24次)。在生地、白芍配伍时当归也出现的概率为95.0%。筛选出甘草、当归、生地和白芍等4味高频次中药抗结核关键靶点基因92个,可能是通过癌症通路(14个基因)、白细胞跨内皮迁移(13个基因)、自然杀伤细胞介导的细胞毒性(10个基因)、ErbB信号通路(10个基因)等来发挥抗结核作用。结论 肺结核的治疗多以补虚药、活血化瘀药、清热药为主,临床治疗可与甘草、当归、生地、白芍等药配伍使用;高频次药物甘草、当归、生地、白芍治疗肺结核的作用机制可能是通过癌症通路、白细胞跨内皮迁移、自然杀伤细胞介导的细胞毒性、ErbB信号通路来实现。     

中药治疗肺结核的用药规律及其核心药物作用机制的探讨

目的: 基于数据挖掘,探讨中药治疗肺结核的用药规律,挖掘出其常用药对,并借助网络药理学探讨其核心药物对肺结核的作用机制。方法: 对符合纳入标准的中药复方建立数据库,运用Apriori算法建立起关联模型,通过中药系统药理分析平台数据库筛选核心药对的活性成分和靶点,应用Gene Cards数据库检索肺结核疾病靶点,分析得到药物-疾病共同靶点,将靶点输入String数据库获得蛋白相互作用网络,通过DAVID数据库进行GO和KEGG通路富集分析,并利用Cytoscape软件对成分-靶点-信号通路进行可视化。结果: 筛选出符合要求的文献156篇,涉及272味中药,频次排名前5位的中药为百部(113次)、麦冬(104次)、黄芪(89次)、白及(86次)、地黄(83次)。关联分析后显示,白及、百部关联性最高(支持度:71.81%,置信度:80.99%,提升比:1.28)。对白及-百部药对进行网络药理学分析,白及-百部发挥的主要作用可能与癌症、乙型肝炎、结核病、凋亡、MAPK、TNF等相关信号通路有关(P值均<0.01)。结论: 通过数据挖掘,白及-百部为治疗肺结核的核心药对。网络药理学初步阐明核心药对白及-百部治疗肺结核的作用机制,可为临床新方组合和新药研发提供思路。     

基于中国医院知识总库手足口病的文献计量学分析

目的运用文献计量学方法对国内医院手足口病(hand-foot-mouth disease,HFMD)的相关文献进行分析,总结文献的分布状态、手足口病的防治现状及研究热点,为该领域的进一步研究提供思路,为患者就医提供参考。方法以中国医院知识总库(China hospital knowledge database,CHKD)为主数据源,同时纳入中国生物医学文献数据库(China biology medicine disc,CBM),检索关键词为“手足口病”的相关文献,利用BitExcel软件去重,Note Express 3.0软件建立“手足口病”文献阅读数据库,CitespaceV软件分析发文量、关键词共现、文献引用、核心作者等情况并进行计量;用Excel软件提取数据并制作图表。分析HFMD的防治现状、热点主题和研究方向。结果入组文献16202篇(基金资助1735篇),博硕论文372篇。2009—2011年年度文献数量变化呈上升趋势,2011—2015年是HFMD研究的高峰期,2016年后文献量逐渐减少;文献的刊载量集中在《现代预防医学》《中国医药指南》《职业与健康》等期刊;中国疾病预防控制中心、河南省疾病预防控制中心等是国内HFMD防控领域的核心机构;郑州市儿童医院、湖南省儿童医院、昆明市儿童医院等在治疗HFMD中积累了丰富的临床经验;HFMD的防治依据《手足口病诊疗指南(2018版)》。研究热点集中在HFMD的治疗、病原学、流行病学及护理等方面。结论HFMD的防治、研究热点和研究方向受到医务人员的关注,此领域的核心期刊、核心机构、核心作者已形成,尚需要更多的基金支持才能保持主题研究的持续性。     

采用宏基因组学分析肺结核患者与健康人群呼吸道微生物菌群的特征

目的 明确肺结核患者和健康人群的呼吸道微生物菌群组成的变化情况。方法 时间限定为2010年1月至2019年12月,在英文数据库(PubMed、Embase and Ovid、Web of Science、Google Scholar、Cochrane Library)和中文数据库(中国知网、万方、中国生物医学文献服务系统与维普)检索所有包含结核和呼吸道菌群的文献,按照文献检索流程筛选文献并最终纳入。收集所有可用的下一代测序数据,统一处理参数,进行数据预处理和系统的宏基因组学分析及统计学处理。结果 共纳入9篇英文文献。物种分析结果提示肺结核组和健康对照组在门水平相对丰度排在前10位的共有菌群有:厚壁菌门、OD1菌门、变形菌门、拟杆菌门、放线菌门、梭杆菌门、蓝菌门。但两组呼吸道菌群群落结构组成差异有统计学意义,α多样性分析显示,肺结核组观测到的可操作分类单元(operational taxonomic units,OTU)数目(286.60±22.82)、Faith 谱系多样性(phylogenetic diversity,PD)指数(Faith PD指数)(13.57±2.58)、Shannon指数(7.17±0.24)明显高于健康对照组(分别为42.88±2.49、6.52±0.22、4.42±0.07),差异均具有统计学意义(P值分别为0.00016、0.00056、0.00016)。肺结核组Chao1指数高于健康对照组(266.50±92.71 和38.44±2.86),但差异无统计学意义(P>0.05)。门水平上两组丰度有差异的物种有6种,其中5种在健康对照组聚集,为厚壁菌门、放线菌门、拟杆菌门、梭杆菌门、变形菌门,另有OD1门在肺结核组聚集。F16科、丙型变形菌纲、梭杆菌门梭杆菌目、厚壁菌门下的明串珠菌科和芽孢杆菌科是肺结核特有的菌群种类。结论 肺结核患者与健康人群比较,呼吸道菌群的多样性及物种组成均发生了较大变化,并具有特有的菌群种类。     

Molecular mechanism of Sishen pills in the treatment of diarrheal diabetic enteropathy based on network pharmacology

This study aimed to explore the effectiveness and safety of Sishen pills for the treatment of diarrheal diabetic enteropathy (DDE).The Traditional Chinese Medicine (TCM) Systems Pharmacology and BATMAN-TCM databases were used to determine the chemical composition of Sishen pills and thus predict information on protein targets. We searched for potential targets of DDE in the GeneCards, DrugBank, Therapeutic Target (TTD), and DisGeNET databases. Using the intersection of the drug and disease targets, protein–protein interaction (PPI) networks and molecular interaction modules were constructed, and key targets were screened. The intersecting gene targets were imported into the Metascape database to conduct Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. The core targets and active ingredients were then docked at the molecular level.Sishen pills contain 70 active ingredients, 463 targets, and 566 disease targets. A module analysis of the targets revealed that the module was mainly related to adrenergic receptor activity, the adenosine phosphate kinase signaling pathway, and the G protein-coupled receptor signaling pathway. The GO and KEGG pathway enrichment results indicated that the protein genes regulated by Sishen pills were mainly enriched in the response to lipopolysaccharides, the AMPK signaling pathway, the JAK-STAT signaling pathway, and other signaling pathways. The molecular docking results showed that the core active compounds exhibited good binding activity with the predicted targets.Sishen pills can regulate the immune function of the body through anti-inflammatory and antibacterial effects for the treatment of DDE.     

基于网络药理学的中药组方“芩部丹”治疗肺结核作用机制研究

目的: 运用网络药理学方法探索中药组方“芩部丹”治疗肺结核的作用机制。方法: 运用中药系统药理学数据库与分析平台(TCMSP)检索黄芩、百部及丹参的药物活性成分及潜在靶点。结合GeneCards、OMIM、TTD及DrugBank数据库搜索肺结核的相关基因靶点。基于Uniprot数据平台对靶点的基因名称进行整理与规范,在STRING 11.0数据平台上生成“芩部丹”治疗肺结核的靶点蛋白互作网络,利用DAVID 6.8平台对靶点进行功能富集与通路分析,利用Cytoscape 3.7.1软件对“芩部丹”治疗肺结核的成分、作用靶点、信号通路进行分析与网络构建。结果: 最终筛选到的“芩部丹”有效化学成分共计116个,作用靶点含有199个。“芩部丹”治疗肺结核的核心活性成分有木犀草素、汉黄芩素、黄芩素、刺槐素、刺芒柄花素、β-谷甾醇、7-甲氧基-3-甲基-2,5-二羟基-9,10-二氢菲,涉及到潜在靶点82个,关键的作用靶点有TP53、IL6、AKT1、VEGFA、EGFR、PTGS2、JUN、CASP3、STAT3、TNF。GO功能富集分析得到生物学过程373条,分子功能66条,细胞组分39条;KEGG通路富集分析获得108条信号通路,关系最密切的为TNF信号通路和细胞凋亡(P值均<0.001),其余包括T细胞受体信号通路、PI3K-Akt信号通路及结核病(P值均<0.001)。结论: 基于网络药理学解释了中药组方“芩部丹”多成分、多靶点、多通路的肺结核治疗机制,为后期的临床与基础研究提供了一定的理论支持。     

基于数据挖掘分析中医治疗老年肛周会阴部坏死性筋膜炎术后用药规律

目的 基于数据挖掘分析中医治疗老年肛周会阴部坏死性筋膜炎术后的用药规律,指导临床用药.方法 检索中文文献库,纳入相关文献.根据分层聚类、关联规则的数据挖掘方法,对高频用药及组方规律进行分析.结果 纳入文献中,有31篇涉及口服方剂,24篇涉及外洗方剂,总共涉及处方107份.高频口服药19味,药对18对,聚类方4则;高频外...     

中西医结合治疗耐多药肺结核的系统评价/Meta分析的再评价

目的 对中西医结合治疗耐多药肺结核的系统评价/Meta分析的文献方法学质量和报告质量进行再评价研究。 方法 通过计算机检索PubMed、EMbase、Cochrane Library、CBM、万方、CNKI和VIP数据库,收集中西医结合治疗耐多药肺结核的系统评价/Meta分析文献,检索时限均从建库至2019年8月。采取主题词和自由词相结合的方式,初步筛选出30篇文献,排除重复发表的15篇文献和非耐多药肺结核的10篇文献,最终纳入5篇文献进行研究。采用AMSTAR量表和GRADE分级评价系统对纳入文献进行方法学质量和报告质量评价。 结果 共纳入5篇系统评价/Meta分析文献,获得8个结局指标,分别为痰菌阴转率、肺部病灶吸收率、空洞闭合率、不良反应发生率、中医证候改善率、治愈率、复发率、治疗有效率。纳入文献均采用中药联合西药与单纯西药治疗进行比较。AMSTAR量表评分显示,3篇分值为6分,属于中等质量;1篇分值为7分,1篇分值为9分,属于高质量。GRADE分级显示,5篇文献的8个结局指标中有1篇痰菌阴转率结局指标证据质量为极低级,其余17个指标为中级(3个)或低级(14个)。5篇文献描述分析结果显示,中西医结合治疗耐多药肺结核,可提高强化期和巩固期的痰菌阴转率及肺部病灶吸收率,改善患者临床症状,提高空洞闭合率,不良反应率相对较低。 结论 中西医结合治疗耐多药肺结核具有协同增效的作用,其系统评价/Meta分析的方法学质量为中高级,但结论的证据强度较低,需加强系统评价的方法学质量和报告质量。     

原发性胆汁性肝硬化中医证候分型文献分析

目的了解现有原发性胆汁性肝硬化临床研究文献中中医证候规律的特点。方法检索中国期刊全文数据库、万方数据库和维普数据库,收集并阅读全文,筛选出符合纳入标准的文献,提取证候类型和辨证依据等资料,进行描述性统计学分析。结果在检索出的78篇文献中,符合纳入条件的文献7篇,所涉及原发性胆汁性肝硬化中医证型共20种,排名在前6位的中医证型分别为：肝郁脾虚（34.85%）、肝肾阴虚（27.82%）、湿热瘀血（6.69%）、湿热蕴结（4.23%）、脾胃气虚（3.87%）和湿滞血瘀（3.52%）;证候分型要素共14个,排名前6位的分别为脾虚（40.49%）、肝郁（39.43%）、肝阴虚（31.34%）、肾阴虚（31.34%）、瘀血（25.70%）和湿热（17.25%）。结论中医研究原发性胆汁性肝硬化的论文水平较低,分型依据缺乏科学性。     

Mechanisms and molecular targets of the Yu-Ping-Feng powder for allergic rhinitis,based on network pharmacology

In traditional Chinese medicine (TCM), Yu-Ping-Feng powder (YPFP) has been used to treat allergic rhinitis (AR) for centuries. However, the mechanisms underlying its effects or its molecular targets in AR treatment are yet to be elucidated. Therefore, the active compounds of YPFP and their targets were collected and identified from the Traditional Chinese Medicine Systems Pharmacology database. Moreover, AR-associated targets were acquired from the GeneCards and Online Mendelian Inheritance in Man database. Proteins interactions network of YPFP presumed targets and AR-associated targets were examined and merged to reveal the candidate YPFP targets against AR.Cytoscape software and BisoGenet Database were employed to perform the Visualization and Integrated Discovery (Cluster Profiler R package, version: 3.8.1). Kyoto Encyclopedia of Genes and Genomes and genome pathway analyses. To identify the key target genes, a gene-pathway network has been constructed.We identified 44 effective active compounds and 622 YPFP targets. Also 1324 target genes related to AR were identified. Twenty pathways, including those of AGE-RAGE signaling, fluid shear stress, atherosclerosis, PI3K-Akt signaling, and tumor necrosis factor signaling was enriched significantly. MAPK1 was identified as the core gene, while others including RELA, AKT1, NFKBIA, IL6, and JUN, were also important in the gene-pathway network. Clearly, network pharmacology can be applied in revealing the molecular targets and mechanisms of action of complex herbal preparations.These findings suggested that YPFP could treat AR by regulating immunological functions, diminishing inflammation, and improving immunity through different pathways.     

基于网络药理学探究络风宁2号方治疗慢性心力衰竭的作用机制

目的 基于网络药理学筛选出络风宁2号方主要活性化合物,预测络风宁2号方治疗慢性心力衰竭(心衰)的潜在作用靶点及信号通路,探讨其作用机制.方法 利用TCMSP平台和相关文献记载检索络风宁2号方中10味药的化学成分和作用靶点;通过GeneCards数据库获取慢性心衰的相关靶标.采用David数据库对交集靶点进行GO功能富集...     

基于网络药理学探讨侯氏黑散治疗缺血性脑卒中的作用机制

目的基于网络药理学探讨侯氏黑散治疗缺血性脑卒中的作用机制。方法采用检索中药系统药理数据库与分析平台(TCMSP)检索侯氏黑散的14味药(牡蛎为动物药,未纳入分析范围)中所有化学成分,筛选活性成分及作用靶点;通过GeneCards检索缺血性脑卒中疾病靶点;利用Venny工具绘制韦恩图,找出交集靶点;应用STRING构建蛋白-蛋白互作(PPI)网络图;通过DAVID数据库对交集靶点进行基因本体(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路富集分析。结果共筛选到155个中药活性成分、164个作用靶点,缺血性脑卒中相关靶点3173个,从而得到药物-疾病的共同靶点121个。富集于分子功能、生物过程和细胞组分及47条信号通路,包括NOD样受体信号通路、胰岛素信号通路、钙信号通路等。预测侯氏黑散居前5位的主要活性成分是前列腺素内过氧化物合酶2、槲皮素、山奈酚、前列腺素内过氧化物合酶1、热休克蛋白90,主要通过调节白细胞介素6(IL-6)、血清对氧磷酶1(PON1)、前列腺素内过氧化物合酶2(PTGS2)、白细胞介素2(IL-2)、趋化因子(CCL2)等靶点,调控NOD样受体信号通路、胰岛素信号通路等达到治疗缺血性脑卒中的目的。结论侯氏黑散通过多成分、多靶点、多通路治疗缺血性脑卒中。     

Network pharmacology-based pharmacological mechanism prediction on Eucommia ulmoides against rheumatoid arthritis

Rheumatoid arthritis (RA) is a common chronic autoimmune disease characterized by synovial inflammation and progressive joint destruction. Eucommia ulmoides (EU) is a kidney-tonifying Chinese medicine that has been applied to treat RA for decides. The present study aims to explore pharmacological mechanisms of EU against RA using network pharmacology approach. Traditional Chinese Medicine Systems Pharmacology (TCMSP) database was used to screen active ingredients of EU, and their relative targets were fished from UniProt database. RA-related targets were screened from GeneCards database and DisGeNET database. The overlapping genes between EU and RA were identified by Venn diagram, and further analyzed for protein-protein interaction (PPI), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG). Fifty active ingredients were identified in EU, and corresponded to 207 targets. Meanwhile, 499 targets were closely associated with RA development. A total of 50 overlapping genes between EU and RA were identified, which were regarded as therapeutically relevant. GO enrichment analysis indicated that EU exerted antiRA effects depending on regulating multiple biological processes including inflammatory response, oxidative stress, cell apoptosis and matrix catabolism. Several key pathways such as TNF pathway, IL-17 pathway, T cell receptor pathway, NOD-like receptor pathway and Toll-like receptor pathway, were involved in the above biological processes. Network pharmacology revealed that EU exerts therapeutic effects on RA through multi-ingredients, multi-targets and multi-pathways, which provides basis for its clinical application and promising directions for subsequent research.     

基于中医传承辅助平台分析头痛的用药规律

背景近几年,头痛发病率越来越高,年龄趋于年轻化,治疗上,西药不良反应多、复发性高,患者依从性差,常达不到预期的治疗效果,因此中医治疗头痛引起人们的重视。中医从整体观念出发,以辨证论治为原则,根据个体差异予以不同的方药治疗,而总结中医治疗头痛的用药规律十分重要。目的运用中医传承辅助平台(V2.5)软件,分析应用中药方剂治疗头痛的用药规律。方法收集中国知网(CNKI)中治疗头痛的有效方剂,以"头痛""偏头痛""紧张型头痛""神经性头痛"为关键词并含"中医"进行搜索,检索2014年1月-2019年10月相关的文献,筛选有效方剂214首。基于中医传承辅助平台(V2.5)软件,建立治疗头痛的组方数据库,采用平台中的"数据分析"系统进行数据挖掘。结果治疗头痛的214首有效方剂涉及中药243味。用药频次居于前5位的中药分别是川芎(149次)、甘草(122次)、白芍(94次)、当归(88次)、白芷(78次)。四气:温性中药用药频次最高,占40.86%(1048/2565),其次是寒、平、凉、热;五味:辛味中药用药频次最高,占33.70%(1315/3902),其次是甘、苦、酸、咸、涩;归经:主要以肝、脾、心为主。挖掘出核心组合16个,新方8首。结论治疗头痛常用活血化瘀类中药,多与益气补血止痛类药物同用,为临床诊疗头痛提供方法及思路,也为进一步研发新药提供参考。     

Network pharmacology explores the mechanisms of Eucommia ulmoides cortex against postmenopausal osteoporosis

Postmenopausal osteoporosis (PMOP) has become one of most frequent chronic disease worldwide with aging population. Eucommia ulmoides cortex (EU), a traditional Chinese medicine, has long since been used to treat PMOP. The aim of this study is to explore pharmacological mechanisms of EU against PMOP through using network pharmacology approach.The active ingredients of EU were obtained from Traditional Chinese Medicine System Pharmacology database, and target fishing was performed on these ingredients in UniProt database for identification of their relative targets. Then, we screened the targets of PMOP using GeneCards database and DisGeNET database. The overlapping genes between PMOP and EU were obtained to performed protein–protein interaction, Gene Ontology analysis, Kyoto encyclopedia of genes, and genomes analysis.Twenty-eight active ingredients were identified in EU, and corresponded to 207 targets. Also, 292 targets were closely associated with PMOP, and 50 of them matched with the targets of EU were considered as therapeutically relevant. Gene ontology enrichment analysis suggested that EU exerted anti-PMOP effects via modulating multiple biological processes including cell proliferation, angiogenesis, and inflammatory response. Kyoto encyclopedia of genes and genomes enrichment analysis revealed several pathways, such as PI3K-AKT pathway, mitogen-activated protein kinase pathway, hypoxia-inducible factors-1 pathway, tumor necrosis factor pathway, and interleukin-17 pathway that might be involved in regulating the above biological processes.Through the method of network pharmacology, we systematically investigated the mechanisms of EU against PMOP. The multi-targets and multi-pathways identified here could provide new insights for further determination of more exact mechanisms of EU.     

基于网络药理学的血必清注射液治疗新型冠状病毒感染合并心肌炎的作用机制研究

目的 基于网络药理学探索血必清注射液作用于新型冠状病毒感染合并心肌炎的主要活性成分及作用机制.方法 利用TCMSP数据库对血必清注射液的主要活性成分及其靶点筛选,再运用GeneCards数据库和OMIM数据库筛选新型冠状病毒感染合并心肌炎的相关靶点,最后对药物靶点和疾病靶点进行Venn分析,得到血必清注射液作用于新型冠...     

基于网络药理学探讨消癥活络方通过ERK5通路抗大鼠肝纤维化的机制

目的基于网络药理学方法探索消癥活络方(XZHLF)防治肝纤维化的作用机制。方法通过TCMSP数据库、化学专业数据库、ETCM数据库、化源网数据库、PubChem数据库以及文献查阅,收集XZHLF各中药化学成分,利用Swiss ADME数据库筛选出XZHLF各中药活性成分,利用Swiss Target Prediction数据库预测XZHLF各中药活性成分靶点;通过GeneCards、OMIN数据库收集肝纤维化疾病靶点,利用韦恩图获得XZHLF防治肝纤维化的潜在作用靶点。使用Cytoscape 3.7.1软件建立XZHLF“药物-活性成分”网络和XZHLF防治肝纤维化的“活性成分-潜在作用靶点”网络。在Metascape数据库对潜在作用靶点进行GO和KEGG富集分析,选取富集基因数最多的前20条绘制气泡图。对前20条KEGG通路中的MAPK信号通路进行分析,绘制“活性成分-潜在作用靶点-通路”网络图。将健康的SD大鼠随机分为6组,分别为空白对照组(K组)、模型组(M组)、秋水仙碱阳性对照组(Y组)、XZHLF高(G组)、中(Z组)、低(D组)剂量组,利用CCl4诱导大鼠肝纤维化进行造模,造模同时给药,共8周。通过Western Blot法检测各组大鼠肝组织内ERK5、p-ERK5、MEK5、MEKK3蛋白的相对含量和表达情况。计量资料多组间比较采用单因素方差分析,进一步两两比较采用LSD-t检验。结果从XZHLF中筛选出110个活性成分,作用于923个活性成分靶点,与6823个肝纤维化疾病靶点相映射得到潜在作用靶点647个。XZHLF可能通过MAPK信号通路等通路,通过MAPK级联反应的调控等生物过程,作用于EGFR、AKT1、IKBKB、MAPK8、PDGFRB等多个蛋白靶点,从而发挥防治肝纤维化的作用。M组的大鼠肝组织内ERK5、p-ERK5、MEK5和MEKK3蛋白水平较K、Y、G、Z、D组明显增加,差异均有统计学意(P值均<0.05);K组的大鼠肝组织内ERK5、p-ERK5、MEK5和MEKK3蛋白水平较Y、G、Z、D组明显减少,差异均有统计学意义(P值均<0.05)。结论基于网络药理学的方法预测出XZHLF可能通过MAPK信号通路防治肝纤维化,通过实验验证XZHLF是通过MAPK信号通路家族中ERK5通路抗肝纤维化。XZHLF高剂量组的抗肝纤维化作用效果最为明显。     

基于网络药理学探究灵宝护心丹治疗急性心肌梗死的潜在机制

目的利用网络药理学和分子模拟对接的方法探究灵宝护心丹治疗急性心肌梗死(AMI)的分子机制。方法通过中药系统药理学数据库(TCMSP)、中医综合数据库(TCMID)获得灵宝护心丹所含9味中药相关活性化合物和作用靶点;通过人类基因数据库Gene Cards获得AMI相关基因,利用String 11.0数据库获得目标基因;利用Cytoscape 3.7.2软件构建化合物-靶标网络,根据拓扑学参数筛选灵宝护心丹治疗AMI的核心靶点;利用Cytoscape 3.7.2插件ClueGO+Cluepedia对疾病和药物交集靶点进行基因本体(GO)生物学过程富集分析和京都基因与基因组百科全书(KEGG)通路注释分析。结果灵宝护心丹化合物-AMI靶点网络包含57个疾病靶点和104个活性化合物,核心靶点包括叉头转录因子(FoxO1)、沉默信息调节因子1(Sirt1)、CASP3、白介素-6(IL-6)、AKT1、SOD2、Bcl2等。GO功能富集得到73个条目;KEGG富集到111个通路,并且被分类为16个具有统计学意义的亚组,主要涉及FoxO信号通路、HIF-1信号通路、凋亡信号通路、NF-κB信号通路等。使用GeneMANIA数据库构建核心靶标蛋白质-蛋白质相互作用(PPI)网络,并对其进行生物学功能分析。利用分子对接模拟软件Autodock Vina 1.1.2,对关键药效分子与核心靶标进行配体-受体对接模拟计算。结论基于网络药理学预测灵宝护心丹治疗AMI的潜在分子机制,为进一步研究其药效和作用机制奠定了基础。     

A database on treating drug addiction with traditional Chinese medicine

AIMS: Traditional Chinese medicine (TCM) has been used to treat drug addiction for more than 160 years and valuable experiences have been accumulated with regard to patients' detoxification and rehabilitation. The aims of this project were (1) to establish a computerized, bilingual (Chinese-English) database on TCM for drug addiction; (2) to analyse the literature published in this field; and (3) to identify those Chinese herbs commonly used for drug addiction treatment. DESIGN: (1) Paper collection: related papers were collected through electronic databases and hand-searched materials; (2) data computerization: the Microsoft Access program and Delphi language were used as the major data management systems; (3) paper analysis: annual publications from 1989 to 2003 were classified and calculated; and (4) herbal analysis: the frequency of herbs used and herbal function categories were analysed. FINDINGS: (1) A special bilingual database that contained 340 works of professional literature, including 85 patent files on TCM for drug addiction, was established, in which more than 90% of the publications originated from mainland China; (2) the literature classification showed a significant increase in the number of publications on clinical and laboratory researches in this field over the past decade; (3) five functional categorizations of Chinese herbs and the 10 most frequently used Chinese herbs as well as three toxic herbs were identified from more than 200 herbs reported in 150 original research articles and 85 patent files. CONCLUSIONS: For the first time, the published data on TCM in the treatment of drug addiction were analysed systematically by using a new database. The results are invaluable for further laboratory and clinical studies to obtain more direct evidence.     

Exploration of potential targets and mechanisms of Naringenin in treating autism spectrum disorder via network pharmacology and molecular docking

Naringenin (NR) is a kind of flavonoid which plays a great role in the treatment of autism spectrum disorder (ASD). However, the underlying mechanism of NR in treating ASD still remains unclear. This study used network pharmacology and molecular docking to examine the potential targets and pharmacological mechanism of NR on ASD. Targets related to NR were screened from Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP), Encyclopedia of Traditional Chinese Medicine Database (ETCM), Traditional Chinese Medicine Integrated Database (TCMID), PharmaMapper database, and targets related to ASD were screened from Online Mendelian Inheritance In Man (OMIM), Disgenet, GeneCards, Therapeutic Target Database (TTD), Drugbank, and ETCM. Screened of the intersected gene targets. Then, we used the protein–protein interaction (PPI) networks to construct a PPI network and used Network Analyzer plug-in to perform topological analysis to screen out the core target. We used Metascape platform to perform gene ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and used Chem draw, Pymol, AutoDock 1.5.6 software for molecular docking verification with core targets. A total of 149 targets of NR and 1594 potential targets of ASD were screened, and 43 intersected targets and 8 key targets were obtained and screened. A total of 176 GO items were obtained by GO enrichment analysis (P < .05), 153 entries on biological process (BP), 12 entries on BP and 11entries on cell composition (CC) were included. A total of 100 signaling pathways were obtained by KEGG pathway enrichment screening (P < .05).The pathways that are closely related to the pathogenesis of ASD are estrogen signaling, thyroid hormone signaling pathway, prolactin signaling pathway, and endocrine resistance pathway. Molecular docking results showed that NR had the best docking activity with the core target CASP3, and had good binding ability with AKT1, ESR1, ACTB and MAPK3. Taken together, our findings support that NR exerts therapeutic effects on ASD with multi-target, and multi-pathway characteristics, which provides a preliminary theoretical basis for clinical trials. The mechanism of anti-oxidative stress response, anti-apoptosis, regulation of cell growth and metabolism, anti-inflammatory, balance hormone levels may be important for the therapeutic effect.