Potential active compounds and molecular mechanism of Xuefu Zhuyu decoction for atherosclerosis,based on network pharmacology and molecular docking

To explore the potential active compounds and molecular mechanism of Xuefu Zhuyu decoction (XFZYD) in the treatment of atherosclerosis (AS) based on network pharmacology and molecular docking.The effective components and action targets of XFZYD were screened by using TCMSP database. And then, the action targets of AS were collected by GeneCards database. The intersection targets between the effective components’ targets of XFZYD and AS-related action targets were used to construct PPI networks. GO and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were performed on these intersection targets. Finally, molecular docking software was used to excavate the active compounds of the core targets VEGFA and AKT1.We detected 225 active components of XFZYD, and found that quercetin, kaempferol, luteolin, naringenin, β-sitosterol, isorhamnetin, stigmasterol, baicalein, nobiletin, and β-carotene are the potential active compounds of XFZYD; STAT3, IL6, JUN, VEGFA, MAPK14, and AKT1 are the core target proteins of the active compounds, among which VEGFA and AKT1 are the key target proteins. PPI network results showed that β-carotene, quercetin, kaempferol, luteolin, and naringenin had higher degree values and more corresponding targets than other 5 active compounds and had the stable binding ability to regulatory proteins VEGFA and AKT1. The core components β-carotene, quercetin, kaempferol, and luteolin exerted their therapeutic effects on AS by acting on the key target proteins VEGFA and AKT1 to regulate fluid shear stress and the AGE-RAGE signaling pathway and IL-17 signaling pathway of diabetic complications of AS. The molecular docking results showed that VEGFA and AKT1 had great docking ability with the targeted active compounds, and β-carotene is the best.The active components of XFZYD, including β -carotene, quercetin, kamanol, and luteolin, can act on VEGFA and AKT1. These active ingredients play a role in alleviating and treating AS by regulating fluid shear stress and participating in signaling pathways such AS AGE-RAGE of atherosclerosis and diabetes mellitus complicated with AS. β-carotene is a potential inhibitor of VEGFA and AKT1 and treats AS through antioxidant action.     

基于网络药理学和分子对接探究余甘子治疗肝细胞癌的分子机制

目的:基于网络药理学及分子对接虚拟预测方法,探究余甘子治疗肝细胞癌的潜在分子机制。方法:通过公共数据库获取余甘子的有效活性成分及作用靶点,并筛选肝细胞癌相关靶点,构建“活性成分-靶点”关系图与PPI网络,进行GO分析和KEGG、Reactome通路富集,采用分子对接评价活性成分与核心靶点的结合活性。结果:共获得19个有效活性成分和12个重要靶点。通过GO分析获得了1794个细胞生物过程,而KEGG和Reactome富集分析分别涉及315和391个相关通路。结论:余甘子的主要有效活性成分为鞣花酸、木犀草素、槲皮素和山奈酚,可能作用于AKT1、MMP9、SRC、ESR1、PPARG和AR等关键靶点,调控内分泌抵抗、癌症中的蛋白多糖、癌症通路、受体酪氨酸激酶信号、白细胞介素信号通路、生长因子受体和第二信使信号转导、PI3K/AKT信号通路等以治疗肝癌。除了直接的肿瘤相关信号通路,间接的炎症、代谢通路在抑制肝癌进展中发挥了重要作用。     

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.     

川芎抗动脉粥样硬化作用机制的网络药理学与分子对接技术研究

目的使用网络药理学与分子对接技术探究川芎抗动脉粥样硬化的作用机制。方法运用中药系统药理(TCMSP)数据库筛选川芎的活性成分及质控成分,通过Swiss Target Prediction预测药物靶点。在DrugBank和DisGeNET数据库筛选出动脉粥样硬化的相关靶点。通过STRING构建靶点蛋白互作网络,运用Cytoscape绘制网络并进行拓扑学分析。使用Omicshare对相关靶点进行GO富集分析与KEGG富集分析。运用DockThor进行分子对接。结果获得川芎抗动脉粥样硬化的167个相关治疗靶点,通过网络拓扑分析发现钙敏感受体、丝裂原活化蛋白激酶3等46个靶点为核心靶点。GO富集分析发现川芎在生物过程、分子功能、细胞组成多方面影响动脉粥样硬化的发生发展。KEGG通路富集分析发现,川芎可能通过调节神经活性配体-受体相互作用、钙信号通路等多条代谢通路来发挥抗动脉粥样硬化的作用。结论运用网络药理学的方法证实了川芎抗动脉粥样硬化具有多途径、多靶点作用的特点。预测了川芎抗动脉粥样硬化的可能机制,为其后续基础研究提供了参考和理论依据。     

基于网络药理学及分子对接技术探讨五苓散治疗慢性心力衰竭的作用机制

目的应用网络药理学及分子对接技术探讨五苓散治疗慢性心力衰竭(CHF)的作用机制。方法在中药系统药理学技术平台(TCMSP)检索五苓散主要成分及对应靶点;检索GeneCards、TTD、DrugBank、DisGeNET数据库,筛选CHF相关靶点;取疾病与药物交集靶点,构建韦恩图;应用Cytoscape 3.8.0软件建立五苓散药物-活性成分-靶点网络及药物成分-交集靶点网络,获得关键化合物;应用STRING平台构建交集靶点蛋白-蛋白相互作用(PPI)的网络图,分析网络图得到关键靶点;应用Metascape数据库对交集基因进行基因本体(GO)及京都基因与基因组百科全书(KEGG)通路富集分析。比较关键靶点及KEGG通路富集基因,选取主要靶点蛋白及关键化合物,应用CB-Dock平台进行分子对接验证。结果通过口服生物利用度(OB)及生物活性分子类药性(DL)筛选得到五苓散共有46个活性成分,共涉及63个作用靶点,与CHF重合的靶点有36个,得到谷甾醇、3β-乙酰氧基-白术酮、二氢槲皮素等10个关键化合物,NOS3、CASP3、PTGS2等10个关键靶点。GO分析得到与循环系统、细胞膜成分及蛋白质相关的注释条目。KEGG通路富集通路主要包括AGE-RAGE信号通路、细胞凋亡、白细胞介素-17(IL-17)信号通路、肿瘤坏死因子(TNF)信号通路等。分子对接结果显示,五苓散关键化合物与新型利尿剂托伐普坦,与治疗靶点均具有良好结合活性。结论五苓散包括多个活性成分,作用于多个靶点,通过抑制细胞凋亡、氧化应激、心肌重构、炎症通路等多种机制作用于CHF,体现了中药治疗疾病多成分、多靶点、多途径的特点。     

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。     

Exploring the mechanism of Xiaoqinglong decoction in the treatment of infantile asthma based on network pharmacology and molecular docking

To explore the mechanism of Xiaoqinglong decoction (XQLD) in the treatment of infantile asthma (IA) based on network pharmacology and molecular docking. The active ingredients of fdrugs in XQLD were retrieved from Traditional Chinese Medicine Systems Pharmacology database and then the targets of drug ingredients were screened. The disease targets of IA were obtained from OMIM and Gencards databases, and the intersection targets of XQLD in the treatment of IA were obtained by Venny 2.1 mapping of ingredient targets and disease targets. Cytoscape software was used to construct active ingredient-intersection target network. The potential targets of XQLD in the treatment of IA were analyzed by protein-protein interaction network using STRING platform, and the Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were obtained by R Studio software. AutoDock was used to perform molecular docking for verification. In this study, 150 active ingredients of XQLD were obtained, including quercetin, kaempferol, β-sitosterol, luteolin, stigmasterol, and so on. And 92 intersection targets of drugs and diseases were obtained, including interleukin 6 (IL6), cystatin 3, estrogen receptor 1, hypoxia inducible factor 1A, HSP90AA1, epidermal growth factor receptor and so on. There were 127 items of Gene Ontology enrichment analysis and 125 Kyoto Encyclopedia of Genes and Genomes enrichment results, showing that apoptosis, IL-17 signaling pathway, tumor necrosis factor signaling pathway, P13K-Akt signaling pathway and other pathways may play a key role in the treatment of IA by XQLD. The results of molecular docking showed that the key active ingredients including quercetin, kaempferol, β-sitosterol, luteolin, stigmasterol, and the core targets including IL6, cystatin 3, estrogen receptor 1, hypoxia inducible factor 1A, HSP90AA1, and epidermal growth factor receptor had good binding activity. Through network pharmacology and molecular docking, the potential targets and modern biological mechanisms of XQLD in the treatment of IA were preliminarily revealed in the study, which will provide reference for subsequent animal experiments and clinical trials.     

Network pharmacology-based strategy to investigate the active ingredients and molecular mechanisms of Scutellaria Barbata D. Don against radiation pneumonitis

Introduction:Herbal medicines combined with radiotherapy significantly reduced the incidence of radiation pneumonitis (RP), and the Scutellaria barbata D. Don (SBD) is a perennial herb that has been reported to protect against radiation-induced pneumonitis. However, the exact molecular mechanism is not known. The objective of this research was to investigate the against radiation pneumonitis ingredients and their functional mechanisms in SBD.Methods:Based on the network pharmacology approaches, we collected active ingredients and target genes in SBD against RP through Traditional Chinese Medicine System Pharmacology (TCMSP) Database, and the “Herb–Ingredients–Target Genes–Disease” Network was constructed by using of Cytoscape. STRING analysis was performed to reveal the protein-protein interactions, and then we applied enrichment analysis on these target proteins, gene function, and pathways.Results:A total of 18 ingredients in SBD regulate 65 RP related target proteins, which show that quercetin, luteolin, baicalein, wogonin may be the key active ingredients, while IL6, AKT1, VEGFA, MMP9, CCL2, prostaglandin-endoperoxide synthase 2 (PTGS2) (cyclooxygenase-2 [COX-2]), CXCL8, IL1B, mitogen-activated protein kinase (MAPK1), and IL10 were identified as critical targets. Besides, the results of Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis indicated that predicted targets of SBD are mostly associated with the pathological process of oxidative stress and inflammation. AGE- Receptor of Advanced Glycation Endproducts (RAGE) signaling pathway in diabetic complications, IL-17 signaling pathway, hypoxia-inducible factor-1 (HIF-1) signaling pathway, NF-kappa B signaling pathway might serve as the principal pathways for RP treatment.Conclusion:In our study, the pharmacological and molecular mechanism of SBD against RP was predicted from a holistic perspective, and the results provided theoretical guidance for researchers to explore the mechanism in further research.     

Network pharmacology-based study of the protective mechanism of conciliatory anti-allergic decoction on asthma

BackgroundThis study aimed to explore the underlying anti-asthma pharmacological mechanisms of conciliatory anti-allergic decoction (CAD) with a network pharmacology approach.MethodsTraditional Chinese medicine related databases were utilized to screen the active ingredients of CAD. Targets of CAD for asthma treatment were also identified based on related databases. The protein-protein interaction network, biological function and KEGG pathway enrichment analysis, and molecular docking of the targets were performed. Furthermore, an asthma mouse model experiment involving HE staining, AB-PAS staining, and ELISA was also performed to assess the anti-asthma effect of CAD.ResultsThere were 77 active ingredients in CAD, including quercetin, kaempferol, stigmasterol, luteolin, cryptotanshinone, beta-sitosterol, acacetin, naringenin, baicalin, and 48 related targets for asthma treatment, mainly including TNF, IL4, IL5, IL10, IL13 and IFN-γ, were identified with ideal molecular docking binding scores by network pharmacology analysis. KEGG pathway analysis revealed that these targets were directly involved in the asthma pathway, Th1 and Th2 cell differentiation, and signaling pathways correlated with asthma (NF-κB, IL17, T cell receptor, TNF, JAK-STAT signaling pathways, etc.). Animal experiments also confirmed that CAD could attenuate inflammatory cell invasion, goblet cell hyperplasia and mucus secretion. The levels of the major targets TNF-α, IL4, IL5, and IL13 can also be regulated by CAD in an asthma mouse model.ConclusionThe anti-asthma mechanism of CAD possibly stemmed from the active ingredients targeting asthma-related targets, which are involved in the asthma pathway and signaling pathways to exhibit therapeutic effects.     

基于网络药理学探讨清痰化瘀方治疗冠心病痰热瘀结证的作用机制

目的运用网络药理学探讨清痰化瘀方治疗冠心病痰热瘀结证的作用机制。方法从中药系统药理学数据库与分析平台(TCMSP)筛选出清痰化瘀方的化学成分和潜在靶点,利用DrugBank、治疗靶点数据库(TTD)、DisGeNET、美国国家生物技术信息中心(NCBI)数据库筛选冠心病靶点,将疾病靶点与药物靶点进行Venn分析,筛选二者共同靶点,应用String数据库构建蛋白-蛋白相互作用网络,并通过DAVID(6.8)数据库对共同靶点进行基因本体(GO)功能富集和京都基因与基因组百科全书(KEGG)通路富集分析,运用Cytoscape 3.5.1构建"中药-化合物-共同靶点-疾病"网络,预测其作用机制。结果通过筛选获得清痰化瘀方101种化学成分和253个作用靶点,共同靶点112个,获得640条生物学过程和108条信号通路。通过对112个靶蛋白进行PPI分析发现,肿瘤坏死因子(TNF)、蛋白激酶(AKT1)、白介素-6(IL-6)、丝裂原活化蛋白激酶(MAPK)3、MAPK8、血管内皮生长因子A(VEGFA)、原癌基因蛋白(FOS)等靶蛋白度值较大,KEGG通路富集结果显示,清痰化瘀方治疗冠心病的较多...     

Analyzing network pharmacology and molecular docking to clarify Duhuo Jisheng decoction potential mechanism of osteoarthritis mitigation

As a classic remedy for treating Osteoarthritis (OA), Duhuo Jisheng decoction has successfully treated countless patients. Nevertheless, its specific mechanism is unknown. This study explored the active constituents of Duhuo Jisheng decoction and the potential molecular mechanisms for treating OA using a Network Pharmacology approaches. Screening active components and corresponding targets of Duhuo parasite decoction by traditional Chinese medicine systems pharmacology database and analysis platform database. Combining the following databases yielded OA disease targets: GeneCards, DrugBank, PharmGkb, Online Mendelian Inheritance in Man, and therapeutic target database. The interaction analysis of the herb-active ingredient-core target network and protein–protein interaction protein network was constructed by STRING platform and Cytoscape software. Gene ontology functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were carried out. PyMOL and other software were used to verify the molecular docking between the essential active components and the core target. 262 active ingredients were screened, and their main components were quercetin, kaempferol, wogonin, baicalein, and beta-carotene. 108 intersection targets of disease and drug were identified, and their main components were RELA, FOS, STAT3, MAPK14, MAPK1, JUN, and ESR1. Gene ontology analysis showed that the key targets were mainly involved in biological processes such as response to lipopolysaccharide, response to xenobiotic stimulus, and response to nutrient levels. The results of Kyoto Encyclopedia of Genes and Genomes analysis show that the signal pathways include the AGE − RAGE signaling pathway, IL − 17 signaling pathway, TNF signaling pathway, and Toll − like receptor signaling pathway. Molecular docking showed that the main active components of Duhuo parasitic decoction had a good bonding activity with the key targets in treating OA. Duhuo Jisheng decoction can reduce the immune-inflammatory reaction, inhibit apoptosis of chondrocytes, strengthen proliferation and repair of chondrocytes and reduce the inflammatory response in a multi-component-multi-target-multi-pathway way to play a role in the treatment of OA.     

Identification of molecular mechanisms underlying the therapeutic effects of Xintong granule in coronary artery disease by a network pharmacology and molecular docking approach

Coronary artery disease (CAD) is a cardiovascular disease characterized by atherosclerosis, angiogenesis, thrombogenesis, inflammation, etc. Xintong granule (XTG) is considered a practical therapeutic strategy in China for CAD. Although its therapeutic role in CAD has been reported, the molecular mechanisms of XTG in CAD have not yet been explored.A network pharmacology approach including drug-likeness (DL) evaluation, oral bioavailability (OB) prediction, protein-protein interaction (PPI) network construction and analysis, and Gene Ontology term and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses was used to predict the active ingredients, potential targets, and molecular mechanisms of XTG associated with the treatment of CAD. Molecular docking analysis was performed to investigate the interactions between the active compounds and the underlying targets.Fifty-one active ingredients of XTG and 294 CAD-related targets were screened for analysis. Gene Ontology enrichment analysis showed that the therapeutic targets of XTG in CAD are mainly involved in blood circulation and vascular regulation. KEGG pathway analysis indicated that XTG intervenes in CAD mainly through the regulation of fluid shear stress and atherosclerosis, the AGE-RAGE signaling pathway in diabetic complications, and the relaxin signaling pathway. Molecular docking analysis showed that each key active ingredient (quercetin, luteolin, kaempferol, stigmasterol, resveratrol, fisetin, gamma-sitosterol, and beta-sitosterol) of XTG can bind to the core targets of CAD (AKT1, JUN, RELA, MAPK8, NFKB1, EDN1, and NOS3).The present study revealed the CAD treatment-related active ingredients, underlying targets, and potential molecular mechanisms of XTG acting by regulating fluid shear stress and atherosclerosis, AGE-RAGE signaling pathway in diabetic complications, and relaxin signaling pathway.     

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。     

Exploring the mechanism of Buyang Huanwu decoction in the treatment of lumbar disc herniation based on network pharmacology and molecular docking

Buyang Huanwu decoction (BYHWD), as one of the traditional Chinese medicine formulas, is widely used in the clinical treatment of lumbar disc herniation (LDH) with curative effect. It has the characteristics of multi-component, multi-target, and mutual synergy, but the mechanism of action is often unclear. It needs some research to explore the molecular mechanism of BYHWD in the treatment of LDH based on network pharmacology and molecular docking. Screen the active compounds of BYHWD and predict drug-related gene/protein targets, which could determine the specific target of BYHWD in the treatment of LDH. Construct the “Drugs-Compounds-Targets” network and search for the core targets. Use Gene Ontology functional enrichment analysis, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and molecular docking verification to explore the possible molecular mechanism. Eighty-two effective compounds and 666 targets of BYHWD, 187 targets for LDH treatment, and 20 core candidate targets were excavated. A total of 3414 entries were identified by Gene Ontology enrichment analysis, 173 related signal pathways were identified by Kyoto Encyclopedia of Genes and Genomes enrichment analysis, and 5 core compounds were identified by molecular docking, which had a good affinity with core genes STAT3, JUN, AKT1, MAPK1, RELA, and PIK3CA. BYHWD may play the role of analgesic and improving function by synergistic anti-inflammatory and analgesic compounds, regulating cell metabolic differentiation, regulating immunity, and anticoagulation. BYHWD in the treatment of LDH may play a role in analgesia and improve function through multiple signaling pathways, including PI3K-Akt, mitogen-activated protein kinase, tumor necrosis factor, and interleukin-17. The PI3K-Akt signaling may be one of the key mechanisms.     

Network pharmacology-based screening of the active ingredients and mechanisms of Huangqi against aging

Studies have shown that Huangqi (HQ) has anti-aging efficacy. However, its active ingredients and mechanisms for anti-aging are still unclear. In this study, we will systematically screen the active ingredients of HQ and explore the possible mechanism of HQ in prevention from aging through network pharmacology technology.The main active ingredients of HQ were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The possible targets were predicted by TCMSP. The related targets for aging were obtained from GeneCards (The Human Gene Database) and Online Mendelian Inheritance in Man (OMIM) database. The common targets of HQ and aging were obtained using R 3.6.3 software. The protein–protein interaction (PPI) network and the ingredient-target-disease network were constructed using Cytoscape 3.7.2 software for visualization. In addition, the Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation of potential targets were performed using R 3.6.3 software.Based on the screening conditions, 16 active ingredients and 28 drug targets were obtained. The PPI network contained 29 proteins, including PTGS2, AR, NOS2, and so on. GO functional enrichment analysis obtained 40 GO items (P < .05). KEGG pathway enrichment analysis obtained 110 aging related pathways (P < .05), including hypoxia inducible factor 1 signaling pathway, PI3K-Akt signaling pathway, AGE-RAGE signaling pathway in diabetic complication, among others.Sixteen effective ingredients of HQ and 28 targets against aging were identified through network pharmacology. Multiple pathways were involved in the effect of HQ on preventing aging.     

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。     

Mechanism research of Salvia miltiorrhiza on treating myocardial ischemia reperfusion injury according to network pharmacology combined with molecular docking technique

Myocardial ischemia reperfusion injury (MIRI) is a kind of complicated disease with an increasing incidence all over the world. Danshen was shown to exert therapeutic effect on MIRI. However, its chemical and pharmacological profiles remain to be elucidated. Network pharmacology was applied to characterize the mechanisms of Danshen on MIRI.The active compounds were screened from the online database according to their oral bioavailability and drug-likeness. The potential proteins of Danshen were collected from the TCMSP database, whereas the potential genes of MIRI were obtained from Gene Card database. The function of gene and pathways involved were researched by GO and KEGG enrichment analysis. The compounds-targets and protein–protein interaction networks were constructed by Cytoscape software. The affinity between active components and potential targets was detected by molecular docking simulation.A total of 202 compounds in Danshen were obtained, and 65 were further selected as active components for which conforming to criteria. Combined the network analysis and molecular docking simulation, the results firstly demonstrated that the effect of Danshen on MIRI may be realized through the targeting of vascular endothelial growth factor A, interleukin-6, and AKT1 by its active components tanshinone IIA, cryptotanshinone, and luteolin. The main regulatory pathways involved may include PI3K/ Akt signaling pathway, HIF-1 signaling pathway, and interleukin-17 signaling pathway. The present study firstly researched the mechanism of Danshen on MIRI based on network pharmacology.The results revealed the multicomponents and multi-targets effects of Danshen in the treatment of MIRI. Importantly, the study provides objective basis for further experimental research.     

非特异性间质性肺炎相关基因筛选和生物信息学分析

目的通过生物信息学的方法筛选非特异性间质性肺炎(nonspecific interstitial pneumonia, NSIP)的致病基因,为进一步研究提供靶点。 方法从GEO数据库下载基因芯片数据集GSE110147、GSE21369、GSE40839,使用limma包分析工具筛选正常组织与NSIP的差异表达基因。通过clusterProfiler包对差异表达基因进行GO分析和KEGG通路富集分析,找到NSIP发病过程中差异表达基因主要参与的生物功能及其集中的信号通路。利用STRING数据库和CYTOSCAPE软件构建蛋白相互作用网络,使用MCODE软件提取蛋白相互作用网络中的子网络模块。 结果3个数据集的差异表达基因做韦恩图得到3个共同差异表达基因。GO富集分析表明NSIP中上调的差异表达基因主要影响RNA剪接、抗病毒感染、对肽的细胞反应等相关的生物过程,富集的分子主要参与细胞组分的囊腔合成分泌、剪接复合体,富集的分子功能主要参与ATP酶活性,受体配体活性及DNA结合转录激活因子活性。NSIP中下调的蛋白主要涉及转移酶活性调节的生物过程。KEGG通路分析表明NSIP中上调的差异表达基因主要参与PI3K-Akt、人类乳头瘤病毒感染及MAPK等信号通路。 结论利用生物信息学筛选出差异表达基因,可能是NSIP发病机制的新靶点,对诊断治疗NSIP具有临床意义。     

基于网络药理学与分子对接技术探究三棱-莪术药对治疗动脉粥样硬化的作用机制

[目的]运用网络药理学与分子对接技术探究三棱-莪术药对治疗动脉粥样硬化(As)的作用机制。[方法]通过TCMSP、Swiss Target Prediction、STRING数据库和Cytoscape软件发现并探究相关治疗靶点的作用关系,通过Omicshare平台进行GO富集分析与KEGG通路富集分析,运用DockThor平台进行分子对接。[结果]研究结果发现158个相关治疗靶点,其中丝氨酸/苏氨酸激酶1、SRC原癌基因、肿瘤坏死因子、丝裂原激活蛋白激酶3、白细胞介素6等49个靶点为核心靶点。GO富集分析发现三棱-莪术药对可以在多方面影响As的发生发展。KEGG通路富集分析发现,三棱-莪术药对可能通过C型凝集素受体信号通路、癌症通路等多条代谢通路来发挥治疗As的作用。分子对接显示靶点TNF与常春藤皂苷元的结合活性最高。[结论]三棱-莪术药对治疗As的作用机制复杂,主要通过C型凝集素受体信号通路、癌症通路等多条代谢通路发挥作用。