Objective:To explore the molecular mechanism of Xuanbai Chengqi Decoction(宣白承气汤)in the treatment of Coronavirus Disease 2019(COVID-19)based on network pharmacology,and to verify by molecular docking technology.Me...Objective:To explore the molecular mechanism of Xuanbai Chengqi Decoction(宣白承气汤)in the treatment of Coronavirus Disease 2019(COVID-19)based on network pharmacology,and to verify by molecular docking technology.Methods:The components and targets of Xuanbai Chengqi Decoction(宣白承气汤)were obtained by TCMSP,targets’information was corrected based on the databases such as UniP rot and DrugBank,and the software Cytoscape3.7.1 was adopted to construct TCM-Component-Target and Component-Target network.The main targets were mapped to the KEGG pathway and the GO biological process with the help of DAVID to further elucidate the potential relationship between the main targets and Xuanbai Chengqi Decoction(宣白承气汤)therapy for COVID-19.In the end,the Swiss Dock platform was adopted for the molecular docking verification of key components and targets.Results:The Component-Target network consists of 35 components and 106 corresponding targets,the main targets include COX-2,NCOA2,PTGS1,HSP90 AB1,PRKACA and PGR,etc.There are 561 GO entries of target mapping(P 0.05),including 155 entries for Biological Processes(BP),147 entries for Cell Composition(CC),and 259 entries for Molecular Function(MF).There are 38 KEGG mapping pathways(P 0.05),including many aspects of infectious disease,immune system and endocrine system,as well as Calcium signaling pathway,VEGF signaling pathway,PI3K-Akt signaling pathway and other processes.Conclusion:The result of molecular docking shows that the affinity of the key components such as beta-sitosterol and stigmasterol are similar to recommended medications for COVID-19.Its effect in the treatment of middle stage of COVID-19 may be related to the blocking of the binding of COVID-19 virus and ACE2,antivirus,and relieving inflammatory storm.展开更多
The current study was designed to explore the brain protection mechanism of Xinglou Chengqi Decoction(XCD)based on gut microbiota analysis and network pharmacology. A transient middle cerebral artery occlusion(MCAO) m...The current study was designed to explore the brain protection mechanism of Xinglou Chengqi Decoction(XCD)based on gut microbiota analysis and network pharmacology. A transient middle cerebral artery occlusion(MCAO) model of mice was established, followed by behavioral evaluation, TTC and TUNEL staining. Additionally, to investigate the effects of gut microbiota on neurological function after stroke, C57BL/6 mice were treated with anti-biotic cocktails 14 days prior to ischemic stroke(IS) to deplete the gut microbiota. High-throughput 16S rDNA gene sequencing, metabonomics technique, and flow multifactor technology were used to analyze bacterial communities, SCFAs and inflammatory cytokines respectively. Finally, as a supplement, network pharmacology and molecular docking were applied to fully explore the multicomponent-multitarget-multichannel mechanism of XCD in treating IS, implicated in ADME screening, target identification, network analysis, functional annotation, and pathway enrichment analysis.We found that XCD effectively improved neurological function, relieved cerebral infarction and decreased the neuronal apoptosis.Moreover, XCD promoted the release of anti-inflammatory factor like IL-10, while down-regulating pro-inflammatory factors such as TNF-α, IL-17A, and IL-22. Furthermore, XCD significantly increased the levels of short chain fatty acids(SCFAs), especially butyric acid. The mechanism might be related to the regulation of SCFAs-producing bacteria like Verrucomicrobia and Akkermansia, and bacteria that regulate inflammation like Paraprevotella, Roseburia, Streptophyta and Enterococcu. Finally, in the network pharmacological analysis, 51 active compounds in XCD and 44 intersection targets of IS and XCD were selected. As a validation, components in XCD docked well with key targets. It was obviously that biological processes were mainly involved in the regulation of apoptotic process, inflammatory response, response to fatty acid, and regulation of establishment of endothelial barrier in GO enrichment. XCD can improve neurological function in experimental stroke mice, partly due to the regulation of gut microbiota. Besises, XCD has the characteristic of "multi-component, multi-target and multi-channel" in the treatment of IS revealed by network pharmacology and molecular docking.展开更多
目的基于网络药理学方法探析桃核承气汤治疗精索静脉曲张的作用机制。方法通过中药系统药理学数据库与分析平台(TCMSP)、UniProt数据库、化源网、PharmMapper数据库筛选桃核承气汤中桃仁、大黄、甘草、桂枝、芒硝5味药物活性化合物和相...目的基于网络药理学方法探析桃核承气汤治疗精索静脉曲张的作用机制。方法通过中药系统药理学数据库与分析平台(TCMSP)、UniProt数据库、化源网、PharmMapper数据库筛选桃核承气汤中桃仁、大黄、甘草、桂枝、芒硝5味药物活性化合物和相关作用靶点,通过GeneCards数据库搜索精索静脉曲张相对应的疾病靶点,使用韦恩图对药物靶点与疾病靶点进行交集获得两者交集靶点,再通过Cytoscape 3.8.2软件构建“药物-成分-靶点-疾病”网络图,将交集靶点导入STRING数据库进行剖析,并绘制蛋白质-蛋白质相互作用(PPI)网络图,通过Metascape数据库对“化合物-疾病”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,在Omicshare云工具将富集结果可视化。结果共得到桃核承气汤活性成分141个,作用靶点230个,精索静脉曲张疾病靶点208个,交集靶点40个,其中起主要作用的活性成分为槲皮素、山萘酚、β-谷甾醇等,核心靶点为丝氨酸/苏氨酸蛋白激酶1(AKT1)、肿瘤坏死因子(TNF)、肿瘤蛋白p53(TP53)等;GO功能富集分析共得到2268个数据条目,其中生物过程(BP)1970个、细胞组分(CC)109个、分子功能(MF)189个,主要涉及对含氧化物的反应(response to oxygen-containing compound)、凋亡过程的调控(regulation of apoptotic process)、程序性细胞死亡的调节(regulation of programmed cell death)等生物过程;KEGG通路富集分析共得到129条代谢通路,主要涉及有癌症相关通路(Pathways in cancer)、流体剪切应力和动脉粥样硬化(Fluid shear stress and atherosclerosis)、乙型肝炎(Hepatitis B)等。结论桃核承气汤治疗精索静脉曲张具有多成分、多靶点、多通路的作用特点,通过抑制炎性反应、促进血管再生、调节细胞生长等以达到治疗精索静脉曲张的效果。展开更多
基金Supported by Wannan Medical College Youth Fund,No.WK201804。
文摘Objective:To explore the molecular mechanism of Xuanbai Chengqi Decoction(宣白承气汤)in the treatment of Coronavirus Disease 2019(COVID-19)based on network pharmacology,and to verify by molecular docking technology.Methods:The components and targets of Xuanbai Chengqi Decoction(宣白承气汤)were obtained by TCMSP,targets’information was corrected based on the databases such as UniP rot and DrugBank,and the software Cytoscape3.7.1 was adopted to construct TCM-Component-Target and Component-Target network.The main targets were mapped to the KEGG pathway and the GO biological process with the help of DAVID to further elucidate the potential relationship between the main targets and Xuanbai Chengqi Decoction(宣白承气汤)therapy for COVID-19.In the end,the Swiss Dock platform was adopted for the molecular docking verification of key components and targets.Results:The Component-Target network consists of 35 components and 106 corresponding targets,the main targets include COX-2,NCOA2,PTGS1,HSP90 AB1,PRKACA and PGR,etc.There are 561 GO entries of target mapping(P 0.05),including 155 entries for Biological Processes(BP),147 entries for Cell Composition(CC),and 259 entries for Molecular Function(MF).There are 38 KEGG mapping pathways(P 0.05),including many aspects of infectious disease,immune system and endocrine system,as well as Calcium signaling pathway,VEGF signaling pathway,PI3K-Akt signaling pathway and other processes.Conclusion:The result of molecular docking shows that the affinity of the key components such as beta-sitosterol and stigmasterol are similar to recommended medications for COVID-19.Its effect in the treatment of middle stage of COVID-19 may be related to the blocking of the binding of COVID-19 virus and ACE2,antivirus,and relieving inflammatory storm.
基金supported by the National Natural Science Foundation of China(No.81704049)“Young Talents”Project of Dongzhimen Hospital of Beijing University of Chinese Medicine(No.DZMYS-201803)。
文摘The current study was designed to explore the brain protection mechanism of Xinglou Chengqi Decoction(XCD)based on gut microbiota analysis and network pharmacology. A transient middle cerebral artery occlusion(MCAO) model of mice was established, followed by behavioral evaluation, TTC and TUNEL staining. Additionally, to investigate the effects of gut microbiota on neurological function after stroke, C57BL/6 mice were treated with anti-biotic cocktails 14 days prior to ischemic stroke(IS) to deplete the gut microbiota. High-throughput 16S rDNA gene sequencing, metabonomics technique, and flow multifactor technology were used to analyze bacterial communities, SCFAs and inflammatory cytokines respectively. Finally, as a supplement, network pharmacology and molecular docking were applied to fully explore the multicomponent-multitarget-multichannel mechanism of XCD in treating IS, implicated in ADME screening, target identification, network analysis, functional annotation, and pathway enrichment analysis.We found that XCD effectively improved neurological function, relieved cerebral infarction and decreased the neuronal apoptosis.Moreover, XCD promoted the release of anti-inflammatory factor like IL-10, while down-regulating pro-inflammatory factors such as TNF-α, IL-17A, and IL-22. Furthermore, XCD significantly increased the levels of short chain fatty acids(SCFAs), especially butyric acid. The mechanism might be related to the regulation of SCFAs-producing bacteria like Verrucomicrobia and Akkermansia, and bacteria that regulate inflammation like Paraprevotella, Roseburia, Streptophyta and Enterococcu. Finally, in the network pharmacological analysis, 51 active compounds in XCD and 44 intersection targets of IS and XCD were selected. As a validation, components in XCD docked well with key targets. It was obviously that biological processes were mainly involved in the regulation of apoptotic process, inflammatory response, response to fatty acid, and regulation of establishment of endothelial barrier in GO enrichment. XCD can improve neurological function in experimental stroke mice, partly due to the regulation of gut microbiota. Besises, XCD has the characteristic of "multi-component, multi-target and multi-channel" in the treatment of IS revealed by network pharmacology and molecular docking.
文摘目的 观察调胃承气汤加减内服与苦参汤外洗联合治疗斑块型银屑病胃肠湿热证的临床疗效。方法 选取2019年6月—2021年6月期间河南省商丘市中医院就诊的斑块型银屑病胃肠湿热证患者90例,按照入院先后顺序进行编号,采用随机数字表法进行分组,编号为单数的45例设为对照组,编号为双数的45例设为治疗组。对照组采用卡泊三醇乳膏、维A酸乳膏外擦,治疗组采用调胃承气汤加减内服与苦参汤外洗。治疗3个疗程后,观察比较两组患者的临床疗效,中医证候评分、银屑病面积与严重程度指数(Psoriasis Area and Severity Index, PASI)评分、生活质量指数(Dermatology Life Quality Index, DLQI)评分,观察比较治疗前后血清炎性因子[白细胞介素-2(Interleukin-2,IL-2)、白细胞介素-4(Interleukin-2,IL-4)及白细胞介素-10(Interleukin-10,IL-10)]水平。结果 治疗后治疗组总有效率93.33%(42/45)明显高于对照组77.78%(35/45),差异有统计学意义(P<0.05)。治疗后两组患者红斑、鳞屑、乏力困倦及瘙痒积分均较治疗前降低,差异有统计学意义(P<0.05);且治疗组红斑、鳞屑、乏力困倦及瘙痒积分均低于对照组,差异有统计学意义(P<0.05)。治疗后两组患者PASI评分及DLQI评分均较治疗前降低,差异有统计学意义(P<0.05);且治疗组患者PASI评分及DLQI评分明显低于对照组,差异有统计学意义(P<0.05)。治疗后两组患者血清IL-2、IL-4及IL-10水平均较治疗前降低,差异有统计学意义(P<0.05);且治疗组患者血清IL-2、IL-4及IL-10水平均明显低于对照组,差异有统计学意义(P<0.05)。结论 调胃承气汤加减内服与苦参汤外洗联用能提高斑块型银屑病胃肠湿热证的治疗有效率,改善中医证候症状,促进皮损消退,改善生活质量,减轻炎症反应。
文摘目的基于网络药理学方法探析桃核承气汤治疗精索静脉曲张的作用机制。方法通过中药系统药理学数据库与分析平台(TCMSP)、UniProt数据库、化源网、PharmMapper数据库筛选桃核承气汤中桃仁、大黄、甘草、桂枝、芒硝5味药物活性化合物和相关作用靶点,通过GeneCards数据库搜索精索静脉曲张相对应的疾病靶点,使用韦恩图对药物靶点与疾病靶点进行交集获得两者交集靶点,再通过Cytoscape 3.8.2软件构建“药物-成分-靶点-疾病”网络图,将交集靶点导入STRING数据库进行剖析,并绘制蛋白质-蛋白质相互作用(PPI)网络图,通过Metascape数据库对“化合物-疾病”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,在Omicshare云工具将富集结果可视化。结果共得到桃核承气汤活性成分141个,作用靶点230个,精索静脉曲张疾病靶点208个,交集靶点40个,其中起主要作用的活性成分为槲皮素、山萘酚、β-谷甾醇等,核心靶点为丝氨酸/苏氨酸蛋白激酶1(AKT1)、肿瘤坏死因子(TNF)、肿瘤蛋白p53(TP53)等;GO功能富集分析共得到2268个数据条目,其中生物过程(BP)1970个、细胞组分(CC)109个、分子功能(MF)189个,主要涉及对含氧化物的反应(response to oxygen-containing compound)、凋亡过程的调控(regulation of apoptotic process)、程序性细胞死亡的调节(regulation of programmed cell death)等生物过程;KEGG通路富集分析共得到129条代谢通路,主要涉及有癌症相关通路(Pathways in cancer)、流体剪切应力和动脉粥样硬化(Fluid shear stress and atherosclerosis)、乙型肝炎(Hepatitis B)等。结论桃核承气汤治疗精索静脉曲张具有多成分、多靶点、多通路的作用特点,通过抑制炎性反应、促进血管再生、调节细胞生长等以达到治疗精索静脉曲张的效果。
