Mechanism of Danggui Sini Decoction(当归四逆汤)for Atherosclerosis Obliterans Based on Network Pharmacology and Molecular Docking

Objective:Based on network pharmacology and molecular docking,we want to explore the pharmacological effects and mechanism of Danggui Sini Decoction in the treatment of lower extremity arteriosclerosis obliterans.Methods:Using TCMSP database to search the main active components of Danggui Sini Decoction(当归四逆汤,DSD)and their related targets,Cytoscape3.8.1 software was used to construct a"component-disease-target"interaction network.Meanwhile,DAVID database was used to enrich the key target genes with GO and KEGG functions.And we used Auto Dock Tools 1.5.6 for molecular docking.Results:A total of 45 candidate active molecules and 250 potential target proteins related to ASO were screened.Key genes such as TNF,IL6,VEGFA,MMP9,IL1B,CCL2,CXCL8,ICAM1,VCAM1,and IL10 are mainly through TNF signaling pathway,HIF-1 signaling pathway,cytokine-cytokine receptor interaction,Toll-like receptor signaling pathway,NF-kappa B signaling pathway,MAPK signaling pathway and other biological pathways exert their effects.The results of molecular docking showed that 5UUI-sesamin,5UUI-paeoniflorin,4XCT-sesamin,and 4XCT-sesamin have extremely strong binding ability.Conclusion:Danggui Sini Decoction(当归四逆汤,DSD)can synergistically exert pharmacological effects through multiple components,multiple targets,and multiple pathways.On the basis of regulating immunity and inhibiting smooth muscle proliferation,it can prevent the occurrence and development of ASO.

Mechanism of Zhenwu Tang in the treatment of diabetic kidney disease based on network pharmacology

Objective:To explore the mechanism of Zhenwu Tang in the treatment of diabetic nephropathy based on network pharmacology.Method:Appling TCMSP database to get the activity of traditional Chinese medicine(TCM)in chemical composition of Zhenwu Tang,and get the target,using of Genecards,OMIM,TTD databases to get the disease related target for diabetic nephropathy,providing database using cytoscape3.7.2 construction of TCM-chemical-disease target network diagram,using the String database to get the corresponding target constructing PPI network,DAVID database is used to obtain the corresponding target GO enrichment analysis and KEGG pathway analysis.Results:Get Zhenwu Tang in active ingredients mainly for beta sitosterol,kaempferol,Stigmasterol,hederagenin,3 beta acetoxyatractylone,core targets including TNF,AKT1 and IL6,involved in biological process(BP)including drug reaction,estradiol,lipopolysaccharide,etc.,It is involved in membrane raft,cave-like depression of cell membrane,plasma membrane,extracellular space and other cellular components(CC),and participates in molecular functions(MF)such as enzyme binding,protein homologous dimerization,heme binding,REDOX enzyme activity,etc.,mainly involving Hepatitis B,TNF signaling pathway,pathway in cancer,etc.Conclusion:This study explored the mechanism of Zhenwu Tang in the treatment of diabetic nephropathy with the method of network pharmacology,providing a theoretical basis for further study of the mechanism of Zhenwu Tang in the treatment of diabetic nephropathy.

Research progress of Sini decoction in pharmacy, pharmacology and clinical application

Sini decoction originated from Zhang Zhongjing's Treatise on Cold Pathogenic and Miscellaneous Diseases(200-210 C.E.)in the Eastern Han Dynasty.It is a traditional and famous prescription in China.Its preparations mainly include Sini decoction,Sini decoction drop pills and Sini decoction suppositories.The main chemical components are diterpenoid alkaloids,gingerol,volatile oil,coumarin,polysaccharide,triterpene saponins,flavonoids,amino acids,and alkaloids.This product has a cardiovascular function,anti-shock,anti-diabetes complications,anti-tumor,anti-atherosclerosis,and effects on the nervous system.Modern clinical practice is widely used in cardiovascular,respiratory,digestive,neurological and gynecological diseases.This paper reviews the pharmaceutical research,pharmacological effects,safety evaluation and clinical application of Sini decoction,including the source and composition of Sini decoction,the origin and resource status of authentic medicinal materials of Sini decoction,the research on preparation form reform,chemical composition and quality control,to provide a reference for further research and clinical promotion of Sini decoction.

Investigation of the mechanism of action of Sanwu Huangqin Tang in the treatment of restless leg syndrome based on network pharmacology,molecular docking technology and molecular dynamics simulation

Background:Through the use of network pharmacology and molecular docking approaches,this study will examine the pharmacological effects of Sanwu Huangqin Tang on restless legs syndrome in order to better understand the mechanism of action of Traditional Chinese medicine(TCM)on RLS.Method:Utilise the TCMSP database to collect and select the drug components of Sanwu Huangqin Tang,and the Uniprot database to identify pertinent targets;RLS-related disease targets were obtained from GeneCards,DrugBank,and OMIM databases;and STRING and Cytoscape 3.9.1 software were used to generate an interaction network.KEGG pathway analysis and GO enrichment analysis were performed utilizing the DAVID database.Use Autodock for analyzing the relationships between targets and core components.Result:By using a network pharmacology approach,83 active ingredients and 50 drug-disease intersecting targets were derived for Sanwu Huangqin Tang.The molecular docking results showed that the drug components had strong affinity with the average target targets.Conclusions:This study provides new insights into the mechanism through which Traditional Chinese Medicine(TCM)treats Restless Legs Syndrome(RLS).Furthermore,it lays the foundation for additional research into the mechanism of treatment for RLS through the intervention that addresses various targets and pathways using the active ingredients identified by Sanwu Huangqin Tang.

Exploration of the mechanism of action of Xiayuxue Tang against hepatic fibrosis based on GEO data mining,network pharmacology and molecular docking technology

Objective:To study the mechanism of action of Xiayuxue Tang in treating hepatic fibrosis by combining GEO data mining,network pharmacology,and molecular docking technology,and provide new research directions for the treatment of hepatic fibrosis.Method:Utilizing multiple databases,we aim to identify the relevant targets of various components in Xiayuxue Tang and their associations with hepatic fibrosis.After pinpointing the key targets through interaction analysis,we will construct both the compound-target network and the protein interaction network for Xiayuxue Tang.Conclusively,we will conduct GO and KEGG enrichment analyses on these key targets,followed by molecular docking verification.Result:Through mining the GEO database,171 related targets were identified.When combined with other databases,a total of 2,343 hepatic fibrosis-related targets were obtained.Xiayuxue Tang comprises 82 related components,which include 26 active components from rhubarb,1 from ground beetle worm,46 from peach kernels,with a total of 314 predicted targets.The GO enrichment analysis revealed 748 biological processes,32 cellular components,and 73 molecular functions,while the KEGG enrichment analysis identified 222 pathways.Molecular docking verification confirmed that effective compounds can bind stably to key proteins,exhibiting strong binding activity.This underscores the potential efficacy of Xiayuxue Tang in addressing hepatic fibrosis.Conclusion:Xiayuxue Tang exerts regulatory effects on hepatic fibrosis through different targets and pathways,suggesting that the herbal compound has the characteristics of multiple pathways and targets.

The Latest Research Advances of Danggui Buxue Tang as an Effective Prescription for Various Diseases: A Comprehensive Review

Danggui Buxue Tang(DBT)is composed of Astragali Radix and Angelicae Sinensis Radix in a weight ratio of 5:1.The recipe of the decoction is simple,and DBT has been widely used in the treatment of blood deficiency syndrome for more than 800 years in China.Studies on its chemical constituents show that saponins,flavonoids,volatile oils,organic acids,and polysaccharides are the main components of DBT.Many techniques such as third-generation sequencing,PCR-denaturing gradient gel electrophoresis,and HPLC-MS have been used for the quality control of DBT.DBT has a wide range of biological activities,including blood enhancement,antagonizing diabetic nephropathy,cardiovascular protection,immunity stimulation,estrogen-like effect,and antifibrosis,among others.In this paper,we summarize the recent research advances of DBT in terms of its components,pharmacological activities,and possible mechanisms of action as well as provide suggestions for further research.

Effect of Sini Decoction plus Ginseng on COVID-19 based on network pharmacological analysis

Objective:To explore the effect of Sini Decoction plus Ginseng on COVID-19 based on network pharmacological analysis.Methods:TCMSP platform was used to search the compounds of Sini Decoction plus Ginseng with oral bioavailability(OB)≥30%and drug-likeness(DL)≥0.18,and the results were input into the UniProt database and converted into standard target names;Genecards and OMIM database were used to find COVID-19 target,and the intersection targets were obtained and Venn diagram was drawn.Cytoscape 3.7.2 was applied to make the network diagram of composition-disease-target;The interaction database platform-String was used to analyze the target protein interaction,and the data were input into the software of Cytoscape 3.7.2 to make the network diagram;David database was used to analyze the accumulation of Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathways of drug-disease intersection targets.The component target pathway network was constructed by using Cytoscape 3.7.2.Results:Altogether,112 active components of Sini Decoction plus Ginseng were screened,corresponding to 234 targets.Besides,261 COVID-19 targets were obtained after screening,and the Venn map showed that 50 targets were intersected.Quercetin,kaempferol,naringenin,andβ-sitosterol were found to have higher moderate values shown by the component-disease-target network.The target proteins with high PPI network analysis value were IL-6,MAPK8,MAPK3,MAPK1,TP53,TNF,and CASP3.GO enrichment function analysis showed that 341 biological processes,33 cell components,and 50 molecular functions were involved,which showed inflammatory reaction,cell response to lipopolysaccharide,exogenous apoptosis signal pathway,positive regulation of RNA polymeraseⅡpromoter transcription,cytokine activity,chemokine activity,heme binding,and other biological processes.KEGG signaling pathway enrichment function analysisshowed that there were 112 signaling pathways.It included TNF signaling pathway,tuberculosis,influenza A,PI3K Akt signaling pathway,HIF-1 signaling pathway,and Toll-like receptor signaling pathway.According to the component-target-pathway network diagram,quercetin,kaempferol,naringenin,andβ-sitosterol in Sini Decoction plus Ginseng may act on IL-6,MAPK8,MAPK3,MAPK1,TP53,TNF,CASP3,and other targets through TNF signaling pathway,MAPK signaling pathway,Tolllike receptor signaling pathway,PI3K-Akt signaling pathway,and HIF-1 signaling pathway.Conclusion:Sini Decoction plus Ginseng can affect COVID-19 through multiple active components,multiple targets,and multiple pathways.

基于网络药理学探讨百合知母汤抗焦虑与失眠的分子机制

目的:应用网络药理学方法探讨百合知母汤抗焦虑与失眠的分子机制。方法:基于中医药整合药理学研究平台(integrative pharmacology-based research platform of traditional Chinese medicine,TCMIP)V2.0对百合知母汤化学成分信息进行靶标预测,将焦虑与失眠相关疾病靶标信息进行蛋白-蛋白互作网络(protein-protein interactions,PPI)构建;富集分析百合知母汤干预焦虑、失眠的关键靶标;构建可视化的“中药方剂-中药材-化学成分-核心靶标-关键通路-疾病关键病理环节”多层次网络关联图。结果:百合知母汤有效成分主要为皂苷、黄酮、挥发油、有机酸等,百合知母汤作用潜在靶标共128个,其中与药物相关靶标14个,与疾病相关靶标114个,药物与疾病共有靶标2个,分别为NR3C1和GABRA1。百合知母汤抗焦虑与失眠主要作用于GABRA1、NFKB1、AR、SMC1A、PIK3CA、NR3C1、DRD2等基因或蛋白靶标中,涉及氨基丁酸、氯离子跨膜运输、突触后膜电位、γ-氨基丁酸的突触传递、神经元凋亡过程负调控及信号转导效应等通路。结论:百合知母汤抗焦虑与失眠的分子作用机制可能与干预GABRA1、NFKB1、DRD2等基因或蛋白表达,调控氨基丁酸、氯离子跨膜运输等通路有关。

基于网络药理学方法、分子对接技术及动物实验探讨参威骨痹汤治疗骨质疏松症的作用机制

目的:探讨参威骨痹汤治疗骨质疏松症(osteoporosis,OP)的作用机制。方法:①网络药理学研究。采用超高效液相色谱-质谱法鉴定参威骨痹汤中的化合物,采用网络药理学方法初步筛选参威骨痹汤治疗OP的关键活性成分和靶点。②分子对接验证。采用分子对接技术验证网络药理学研究确定的参威骨痹汤治疗OP的关键活性成分与靶点的结合效果,从中筛选结合效果最好的组合。③动物实验验证。将60只雌性C57BL/6JNifdc小鼠随机等分为5组,模型组和参威骨痹汤低、中、高剂量组小鼠通过双侧卵巢切除手术进行OP造模,假手术组小鼠仅切取卵巢周围等体积的脂肪组织。参威骨痹汤低、中、高剂量组小鼠分别按照14.95 g·kg^(-1)·d^(-1)、29.9 g·kg^(-1)·d^(-1)、59.8 g·kg^(-1)·d^(-1)以参威骨痹汤药液灌胃,假手术组和模型组小鼠以等体积生理盐水灌胃。药物干预8周后,取股骨进行Micro-CT检查和组织病理学观察(HE染色和抗酒石酸酸性磷酸酶染色),采用实时定量PCR技术测定胫骨组织中根据网络药理学和分子对接技术确定的关键靶点基因的mRNA表达水平。结果:①网络药理学研究结果。网络药理学研究结果显示,SRC、促分裂原活化的蛋白激酶3(mitogen-activated protein kinase 3,MAPK3)、MAPK1、磷脂酰肌醇3-激酶调节亚基1(phosphatidylinositol-3-kinase regulatory subunit 1,PI3KR1)、信号转导及转录活化因子3为参威骨痹汤治疗OP的关键靶点,五味子丙素、10-姜酚、对羟基苯甲酸丁酯、倍半萜内酯和香豆雌酚为参威骨痹汤治疗OP的关键活性成分。②分子对接验证结果。分子对接结果显示,参威骨痹汤治疗OP关键活性成分与关键靶点的结合能均小于-5 kJ·mol^(-1),表明结合效果良好,其中靶点SRC、MAPK3、PI3KR1与活性成分五味子丙素、10-姜酚、对羟基苯甲酸丁酯的结合效果更好。③动物实验验证结果。Micro-CT检查及组织病理学观察结果显示,参威骨痹汤能改善OP模型小鼠的骨质疏松程度,其中中剂量参威骨痹汤效果更好。实时定量PCR测定结果显示,参威骨痹汤中剂量组胫骨组织中SRC mRNA和MAPK3 mRNA表达水平低于模型组,PI3KR1 mRNA表达水平与模型组比较差异无统计学意义。结论:参威骨痹汤治疗OP的机制可能是通过五味子丙素、10-姜酚、对羟基苯甲酸丁酯等成分调控SRC、PI3KR1、MAPK3的表达来调节骨代谢。

王振亮运用四逆汤治疗成人斯蒂尔病经验

成人斯蒂尔病是一种多因素参与的自身炎症性疾病,以发热、皮疹、关节疼痛和多器官受累为特点,目前尚无根治办法。西医治疗以非甾体类抗炎药、糖皮质激素、免疫抑制剂及生物制剂治疗为主。王振亮教授认为阳虚寒凝血瘀是成人斯蒂尔病核心病机,临床表现以阴阳不和、寒凝血瘀为主,也常夹湿、郁热,病位在半表半里,病性寒热错杂,以温阳益气立法,以四逆汤为核心方,同时重视顾护脾胃以及治血药的运用,谨守病机随证配伍,灵活运用。

基于网络药理学及动物实验研究祛风汤治疗肛周湿疹的作用机制

目的:基于网络药理学方法探究祛风汤治疗肛周湿疹的作用机制,并通过动物实验对关键靶点及信号通路进行验证。方法:应用中药系统药理学数据库与分析平台(TCMSP)数据库获得祛风汤10味中药相关活性成分及作用靶点;通过GeneCards数据库和OMIM数据库筛选肛周湿疹的疾病靶点,并采用Venny 2.1.0在线软件作图工具平台获取两者交集基因;基于String数据库构建祛风汤治疗肛周湿疹交集靶点PPI网络,并通过构建Hub网络筛选核心靶点。应用DAVID6.8数据平台对交集靶点的基因本体论(GO)生物学过程富集分析和京都基因与基因组百科全书(KEGG)通路进行注释分析。通过Cytoscape构建祛风汤“活性成分-靶点-通路”网络筛选主要活性成分。构建肛周湿疹小鼠模型,验证祛风汤治疗肛周湿疹的关键靶点及信号通路。结果:祛风汤共有135个活性成分,对应268个作用靶点,其中35个作用靶点与治疗肛周湿疹有关。PPI网络分析得到白细胞介素-6(IL-6)、肿瘤坏死因子(TNF)、CXCL8(IL-8)等核心靶点。GO富集分析共得到267个条目;KEGG富集分析共筛选得到60条通路,主要涉及TNF信号通路、核因子κB(NF-κB)信号通路、类风湿关节炎等。动物实验结果显示,祛风汤可改善肛周湿疹小鼠皮肤损伤,减少局部炎症浸润;祛风汤能减少肛周湿疹小鼠血清IL-6含量(P<0.05),下调湿疹皮肤组织中NF-κB信号通路相关蛋白NF-κB和TNF-α表达水平(P<0.05)。结论:祛风汤治可能通过调控NF-κB信号通路发挥疗治疗肛周湿疹的作用。

基于网络药理学和分子对接方法研究清养活血汤治疗卒中相关性肺炎的作用机制

目的 基于网络药理学和分子对接技术探究清养活血汤治疗卒中相关性肺炎(SAP)的分子作用机制。方法 采用中药系统药理学数据库与分析平台(TCMSP)筛选清养活血汤的活性成分及潜在作用靶点,利用GeneCards、OMIM、PharmGkb、TTD和DrugBank数据库检索SAP疾病的靶点,并通过R软件“venn”包对药物潜在作用靶点与疾病相关作用靶点取交集得到共同作用靶点。利用Cytoscape软件及STRING数据库,建立清养活血汤治疗SAP的潜在活性成分-靶点调控网络模型及交集靶点蛋白互作网络,分析网络中关键靶点基因及对应药物活性成分。通过基因本体(GO)功能分析和京都基因与基因组百科全书(KEGG)通路富集分析。利用分子对接技术验证核心成分与靶蛋白分子的对接情况。结果 TCSMP数据库筛选得到清养活血汤共15味中药,有效活性成分160个,作用靶点447个,筛选得到SAP疾病潜在靶点4 425个,作用于该疾病的潜在靶点282个,核心作用靶点21个。GO富集分析显示,在生物学进程,关键靶点基因主要富集于脂多糖的反应,在分子功能和细胞成分上,关键靶点基因主要富集于核受体活性和膜筏等方面;KEGG富集分析表明,关键靶点基因主要富集于脂质和动脉粥样硬化和AGE-RAGE信号通路。通过分子对接显示,清养活血汤主要活性成分与核心靶蛋白结合具有较好的亲和力。结论 清养活血汤具有多活性成分,能够通过抗炎、抗氧化、改善血管功能等多种途径发挥治疗SAP的作用,可为临床清养活血汤治疗SAP进一步研究提供科学依据。

基于网络药理学及分子对接探讨四逆散对溃疡性结肠炎与抑郁症“异病同治”的作用机制

目的 基于网络药理学及分子对接探讨四逆散对溃疡性结肠炎与抑郁症“异病同治”的作用机制。方法 利用TCMSP数据库获取四逆散的潜在活性成分及其相关作用靶点;利用GeneCards、CTD、TTD数据库筛选溃疡性结肠炎和抑郁症的疾病相关靶点;对上述预测得到的活性成分作用靶点与疾病相关靶点取交集,获得四逆散治疗溃疡性结肠炎和抑郁症的潜在作用靶点(共有靶点),采用Cytoscape 3.7.2软件构建“中药-活性成分-疾病-共有靶点”网络,分析核心成分;将共有靶点导入STRING数据库,构建共有靶蛋白相互作用(PPI)网络,分析关键靶点;通过DAVID数据库对共有靶点进行GO功能及KEGG通路富集分析;对核心成分与关键靶点进行分子对接验证。结果 共获得四逆散的活性成分136个,四逆散治疗溃疡性结肠炎和抑郁症的潜在作用靶点(共有靶点)220个,涉及657个生物过程、70个细胞组分、147个分子功能以及133条信号通路。筛选得到槲皮素、山柰酚、木犀草素、柚皮素、7-甲氧基-2-甲基异黄酮等核心活性化合物,JUN、MAPK3、STAT3、AKT1、MAPK1等关键靶蛋白,以及TNF、IL-17、Th17细胞分化、HIF-1、Toll样受体等信号通路。5个关键靶点均与槲皮素、山柰酚、木犀草素、柚皮素有较强的结合活性。结论 四逆散可能是通过槲皮素、山柰酚、木犀草素、柚皮素等活性成分,作用于JUN、MAPK3、STAT3、AKT1、MAPK1等关键靶点,通过TNF、IL-17、HIF-1、Toll样受体、Th17细胞分化等信号通路,发挥对溃疡性结肠炎与抑郁症“异病同治”的作用。

基于网络药理学探讨知柏地黄汤化裁方治疗性早熟的分子机制研究

目的 目的 采用网络药理学探讨知柏地黄汤化裁方防治特发性中枢性性早熟(idiopathic central precocious puberty,ICPP)的分子机制。方法 使用中药系统平台搜集知柏地黄汤化裁方单味药活性成分;PubChem数据库和Uniprot数据库获取知柏地黄汤化裁方的主要活性成分靶基因;DisGeNET数据库获取ICPP的靶点;STRING数据库和Cytoscape软件构建蛋白相互作用网络模型及KEGG代谢通路分析;PyMOL软件绘图。结果 获得活性成分61个,与疾病的交集基因靶点13个,涉及的重要信号通路3条。结论 知柏地黄汤化裁方主要通过多成分、多靶点、多通路发挥对ICPP的治疗作用,为临床治疗提供一定的理论依据。

四逆散药理作用及治疗内科疾病的临床应用研究

四逆散为《伤寒论》中记载的经典名方,至今约有1800年的历史,适用于少阴病症,临床多以手足不温、泄利下重、腹痛、脉弦等为辨证要点,具有透邪解郁、疏肝理脾之功效。中医认为该方剂治疗病症与阳衰阴盛有本质的区别,该证属外邪传经入里,气机为之郁遏,失于疏泄,阳气内郁不能达于四末所致,为阴中涵阳、惟气不宣通而致四肢逆冷。四逆散的应用十分广泛,几乎各系统疾病均可以该方剂为基础方进行辨证施治,尤其是现临床对四逆散的研究更加深入,其药理作用和应用领域也进一步被拓展,可广泛用于治疗胃肠肝胆疾病、精神类疾病、肿瘤疾病等。文章通过分析近年来四逆散的应用文献,总结其药理和治疗作用,为临床对四逆散有更加深入地了解,推动该方剂在临床的进一步开发应用。

基于网络药理学及动物实验研究温肾宣痹汤抗骨质疏松的机制

目的应用网络药理学、分子对接及体内实验技术,预测以及验证温肾宣痹汤(wenshen xuanbi tang,WSXBT)抗骨质疏松(osteoporosis,OP)的作用机制。方法利用网络药理学筛选WSXBT治疗OP的关键成分及核心靶点,Metascape数据库对核心靶点进行基因本体论(gene ontology,GO)功能分析和京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)通路富集分析,AutoDockTools 1.5.7软件进行分子对接模拟关键活性成分与核心靶点的结合活性。切除大鼠双侧卵巢建立OP大鼠模型,研究WSXBT对OP大鼠的药效及验证相关靶点通路。酶联免疫吸附(ELISA)法检测血清中OPG、PINP、RANKL水平,生物力学测试仪测定大鼠股骨生物力学,Micro-CT检测股骨骨密度,进而通过Western blot法检测PI3K和Akt的蛋白表达水平。结果筛选出WSXBT活性成分156个,涉及229个潜在作用靶点,筛选核心靶点23个,共涉及145条信号通路;分子对接结果显示,槲皮素、异补骨脂黄酮、β-谷甾醇等关键成分与PIK3R1、AKT1核心靶点均拥有良好的结合能力。体内实验结果表明,WSXBT可明显升高OP大鼠骨密度,改善OP大鼠骨组织微结构,提高大鼠股骨生物力学,增加大鼠PINP表达及OPG/RANKL比值,Western blot结果显示,WSXBT可明显升高p-PI3K/PI3K、p-Akt/Akt比值。结论WSXBT可能通过PI3K/Akt信号通路及升高OPG/RANKL比值改善绝经后OP大鼠骨密度。

当归四逆汤物质基础研究进展

当归四逆汤是治疗血虚寒厥证的代表方剂,具有温经散寒、养血通脉等功效。现代研究发现,其具有抗凝及抗血栓形成、改善末梢及全身血液循环、抗炎镇痛、解痉、提高神经传导速度等药理活性。在对当归四逆汤化学成分、药理作用综述的基础上,基于传统植物化学分离分析、血清药物化学、代谢组学、谱效关系、网络药理学和多靶点高通量筛选等技术方法,对当归四逆汤的药效物质基础予以总结和分析,为当归四逆汤的深入开发及相关制剂的质量控制等后续研究提供参考。参考文献49篇。

基于网络药理学的二仙汤“异病同治”乳腺增生和围绝经期综合征的作用机制

目的:基于网络药理学探讨二仙汤“异病同治”乳腺增生和围绝经期综合征的作用机制。方法:通过中药系统药理学数据库与分析平台(traditional Chinese medicine systems pharmacology database and analysis platform,TCMSP)筛选二仙汤中6味中药的活性成分并预测其潜在靶点;通过人类基因数据库(the human gene database,GeneCards)及在线人类孟德尔遗传数据库(online mendelian inheritance in man,OMIM)平台检索乳腺增生和围绝经期综合征的疾病靶点,借助Venn在线工具构建药物与两种疾病的交集靶点。运用Cytoscape 3.7.2软件构建“药物-成分-靶点-疾病”网络;利用STRING数据库构建PPI网络,按Dgree值大于等于平均值进一步筛选核心靶点;采用DAVID数据库进行基因本体论(gene ontology,GO)富集分析,同时实现京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)通路富集分析。结果 :根据口服生物利用度(oral bioavailability,OB)≥30%和药物类药性(druglikeness,DL)≥0.18筛选得到二仙汤有效活性成分104个,预测潜在作用靶点147个;通过筛选得到乳腺增生靶点4153个,围绝经期综合征靶点155个,药物与疾病的交集靶点29个,其中IL-6、VEGFA、TNF、TP53、ESR1、CAT、IL-1β等可能是二仙汤治疗乳腺增生和围绝经期综合征的关键靶点。活性成分及靶点主要参与DNA模板转录正调控、基因表达的正调控、胞外间隙、胞外区、类固醇结合、酶结合等;靶基因主要富集在TNF、NOD样体、HIF-1、癌症、PI3K-Akt等信号通路。结论:二仙汤可能通过调控PI3K-Akt、HIF-1等信号通路达到防治乳腺增生和围绝经期综合征的目的。

基于网络药理学和实验验证探讨麦门冬汤治疗特发性肺纤维化的作用机制

目的:利用网络药理学方法并结合实验研究,深入探究麦门冬汤对特发性肺纤维化的治疗作用及其机制。方法:采用中药系统药理学数据库TCMSP、中国传统医学百科全书ETCM和SwissADME筛选并确定麦门冬汤中的活性成分。接着利用PubChem、SwissTargetPrediction和Uniport数据库挑选出中药活性成分的潜在作用靶标。借助GeneCards和OMIM数据库获取特发性肺纤维化的靶点基因。Venn diagrams绘图工具筛选出中药与疾病的交集靶点,利用Cytoscape3.9.1软件构建“中药-活性成分-疾病-靶点”网络关系图,并通过CytoNCA插件构建蛋白质相互作用网络,筛选得到核心靶点蛋白。运用DAVID进行GO及KEGG通路富集分析。最后使用博来霉素建立SD大鼠肺纤维化模型,观察大鼠肺组织肉眼标本及病理切片,并对其进行实时荧光定量PCR分析,比较治疗组与对照组TGF-β1、α-SMA、IL-4、IFN-γ、LC3-Ⅱ、beclin1的mRNA表达水平。结果:本研究共筛选得到麦门冬汤治疗IPF的作用靶点402个,其中核心靶点50个,对应5种中药的159种有效成分。GO富集分析和KEGG富集分析涉及PI3K-AKT信号通路、MAPK信号通路等信号通路治疗特发性肺纤维化。动物实验结果显示,与模型对照组相比,麦门冬汤治疗组可显著下调TGF-β1、α-SMA、IL-4 mRNA的相对表达水平(P<0.05),显著上调LC3-Ⅱ、beclin1、IFN-γmRNA的相对表达水平(P<0.05)。结论:本研究提示,麦门冬汤中关键活性成分可能在细胞自噬、炎症反应、巨噬细胞极化等生物过程方面发挥作用,发挥改善肺纤维化的作用。

四逆散药理作用研究进展及质量标志物(Q-marker)预测分析

四逆散由炙甘草、柴胡、白芍、枳实组成,具有透邪解郁、疏肝理脾的功效。现代药理学研究表明该药具有抗抑郁、保肝、治疗功能性消化不良、改善动脉硬化、镇静催眠及抗溃疡等药理作用。本文在对四逆散药理作用的研究进展进行总结的基础上,依据中药质量标志物(qualitymarker,Q-marker)的“五原则”对四逆散的Q-marker进行预测分析。结果提示甘草苷、甘草素、甘草次酸、甘草酸、山柰酚、槲皮素、柚皮苷、柴胡皂苷a、柴胡皂苷d、芍药苷、芍药内酯苷、橙皮苷、新橙皮苷、辛弗林可考虑作为四逆散的Q-marker,以期为四逆散质量控制研究提供参考。