Background:Ischemic stroke(IS)is a global health issue and the current treatment options for IS are inadequate.Buyang Huanwu decoction(BHD)has demonstrated effectiveness in treating IS.However,the mechanisms by which ...Background:Ischemic stroke(IS)is a global health issue and the current treatment options for IS are inadequate.Buyang Huanwu decoction(BHD)has demonstrated effectiveness in treating IS.However,the mechanisms by which BHD treats IS remain unclear,and no studies have been conducted to analyze these mechanisms from the perspective of Cuproptosis.In order to investigate the potential of BHD to intervene in IS through Cuproptosis,this study employed a systematic pharmacological approach and molecular docking verification.Methods:To investigate the mechanism of BHD in treating IS through Cuproptosis,relevant information on the structure,targets,and major biological functions and pathways of compounds related to BHD was collected from databases such as PubChem,PharmMapper,UniProt,and GeneCards.The results were then visualized using Cytoscape3.6.1,Ledock,and pymol software.Results:BHD is composed of 7 Chinese medicines,which contain 82 compounds,including 10 core compounds.These compounds are associated with 241 genes,of which 97 are common to BHD,IS,and Cuproptosis.The 97 common genes,including 10 core genes,are involved in biological processes such as proteolysis,regulation of apoptosis and cholesterol storage,as well as cellular components and molecular functions.The common genes among BHD,IS,and Cuproptosis,including 10 core genes,participate mainly in Kyoto Encyclopedia of Genes and Genomes pathways such as pathways in cancer,PI3K-Akt signaling pathway,and Estrogen signaling pathway.According to molecular docking results,linolenic acid showed good docking scores with 9 out of 10 core genes,except for SRC.13-hydroxy-9,11-octadecadienoic acid also demonstrated good docking scores with EGFR,MAPK14,and F2.Similarly,senkyunone also had good docking scores with EGFR,MAPK14,and F2,all of which had docking energy greater than−5 kcal.Conclusion:In this study,the potential of BHD for treating IS through Cuproptosis and its underlying mechanisms were explored and partially validated through molecular docking.However,due to the limitations of the systems pharmacology research method,further validation through cell experiments,animal experiments,and clinical trials may be necessary to confirm these findings.展开更多
目的:运用网络药理学方法建立补阳还五汤靶点-疾病网络,挖掘补阳还五汤治疗勃起功能障碍(erectile dysfunction,ED)的作用机制。方法:运用中药系统药理学数据库与分析平台(traditional Chinese medicine systems pharmacology database ...目的:运用网络药理学方法建立补阳还五汤靶点-疾病网络,挖掘补阳还五汤治疗勃起功能障碍(erectile dysfunction,ED)的作用机制。方法:运用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)收集补阳还五汤组成药物的主要活性成分,采用Swiss target prediction和TCMSP靶点预测工具预测药物成分潜在作用靶点,在GENECARDS等多个数据库获取ED相关靶标。寻找复方成分与疾病共有靶标,应用拓扑分析明确重要靶点,借助AVID在线工具进行关键作用靶点的基因本体论功能富集分析(gene ontology,GO)和KEGG富集(kyoto encyclopedia of genes and genomes,KEGG)分析。最后通过Cytoscape 3.5.1构建补阳还五汤中药-靶点-疾病可视化网络图。结果:补阳还五汤中共收集到符合条件的活性成分73个,其中黄芪18个,当归尾2个,赤芍14个,川芎6个,桃仁18个,红花15个。这些活性成分有621个潜在靶标,ED疾病靶标308个,补阳还五汤靶标基因与ED疾病靶标基因的交集基因有71个,其中hub节点36个。对这36个关键作用靶点进行整合分析发现,补阳还五汤主要通过细胞因子与细胞因子受体的相互作用、PI3K-Akt信号通路、肿瘤坏死因子信号通路、核转录因子κB信号通路、HIF-1信号通路、NOD样受体信号通路、Jak-STAT信号通路、p53信号通路、前列腺癌等途径实现对基因表达的干预,从而治疗ED。结论:网络药理学方法揭示补阳还五汤治疗ED是多成分、多靶点、多条信号通路共同作用的结果。展开更多
Objective:The objective of this study was to investigate the molecular mechanism of Buyang Huanwu decoction(BYHWD)in the treatment of diabetic foot(DF).Methods:The TCMSP,BATMAN,PubChem,PharmMapper,UniProt,GeneCards,We...Objective:The objective of this study was to investigate the molecular mechanism of Buyang Huanwu decoction(BYHWD)in the treatment of diabetic foot(DF).Methods:The TCMSP,BATMAN,PubChem,PharmMapper,UniProt,GeneCards,Webgestalt,and Kobas databases were used to obtain the structures,targets,main biological functions,and pathways of the active ingredients of BYHWD,and the results were visualized using Cytoscape3.6.1,Ledock,and PyMol software.Results:A total of 82 active components of BYHWD and 193 targets related to BYHWD were identified,and 5295 genes related to DF were identified using the GeneCards database,including 65 key targets of BYHWD in the treatment of DF.GO and KEGG enrichment analyses of the 65 targets for BYHWD treatment of DF showed that 47 GO items were involved in the treatment.It was mainly involved in biological processes,such as biological regulation,metabolism,and stress response.It is primarily involved in protein binding,ion binding,nucleotide binding,and other molecular functions.It is mainly involved in membrane encapsulation,membrane lumen closure,and other biological components and involved in the VEGF,TNF,RAS,RAP1,PI3K-AKT,MAPK,and IL-17 signaling pathways.Most targets were enriched in the PI3K-AKT and MAPK signaling pathways.Molecular docking results showed that the 59 key active components of BYHWD had strong binding activity with 64 key DF targets.Conclusion:The therapeutic effect of BYHWD on DF is based on the pharmacological effects of multiple targets and pathways.展开更多
基金This study was funded by the National Natural Science Foundation of China(81874416)Hunan Science and Technology Innovation Team Project(2020RC4050)+1 种基金Hunan Provincial Innovation Foundation for Postgraduate(CX20220788)Foshan Medical Research Fund(20210311).
文摘Background:Ischemic stroke(IS)is a global health issue and the current treatment options for IS are inadequate.Buyang Huanwu decoction(BHD)has demonstrated effectiveness in treating IS.However,the mechanisms by which BHD treats IS remain unclear,and no studies have been conducted to analyze these mechanisms from the perspective of Cuproptosis.In order to investigate the potential of BHD to intervene in IS through Cuproptosis,this study employed a systematic pharmacological approach and molecular docking verification.Methods:To investigate the mechanism of BHD in treating IS through Cuproptosis,relevant information on the structure,targets,and major biological functions and pathways of compounds related to BHD was collected from databases such as PubChem,PharmMapper,UniProt,and GeneCards.The results were then visualized using Cytoscape3.6.1,Ledock,and pymol software.Results:BHD is composed of 7 Chinese medicines,which contain 82 compounds,including 10 core compounds.These compounds are associated with 241 genes,of which 97 are common to BHD,IS,and Cuproptosis.The 97 common genes,including 10 core genes,are involved in biological processes such as proteolysis,regulation of apoptosis and cholesterol storage,as well as cellular components and molecular functions.The common genes among BHD,IS,and Cuproptosis,including 10 core genes,participate mainly in Kyoto Encyclopedia of Genes and Genomes pathways such as pathways in cancer,PI3K-Akt signaling pathway,and Estrogen signaling pathway.According to molecular docking results,linolenic acid showed good docking scores with 9 out of 10 core genes,except for SRC.13-hydroxy-9,11-octadecadienoic acid also demonstrated good docking scores with EGFR,MAPK14,and F2.Similarly,senkyunone also had good docking scores with EGFR,MAPK14,and F2,all of which had docking energy greater than−5 kcal.Conclusion:In this study,the potential of BHD for treating IS through Cuproptosis and its underlying mechanisms were explored and partially validated through molecular docking.However,due to the limitations of the systems pharmacology research method,further validation through cell experiments,animal experiments,and clinical trials may be necessary to confirm these findings.
文摘目的:运用网络药理学方法建立补阳还五汤靶点-疾病网络,挖掘补阳还五汤治疗勃起功能障碍(erectile dysfunction,ED)的作用机制。方法:运用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)收集补阳还五汤组成药物的主要活性成分,采用Swiss target prediction和TCMSP靶点预测工具预测药物成分潜在作用靶点,在GENECARDS等多个数据库获取ED相关靶标。寻找复方成分与疾病共有靶标,应用拓扑分析明确重要靶点,借助AVID在线工具进行关键作用靶点的基因本体论功能富集分析(gene ontology,GO)和KEGG富集(kyoto encyclopedia of genes and genomes,KEGG)分析。最后通过Cytoscape 3.5.1构建补阳还五汤中药-靶点-疾病可视化网络图。结果:补阳还五汤中共收集到符合条件的活性成分73个,其中黄芪18个,当归尾2个,赤芍14个,川芎6个,桃仁18个,红花15个。这些活性成分有621个潜在靶标,ED疾病靶标308个,补阳还五汤靶标基因与ED疾病靶标基因的交集基因有71个,其中hub节点36个。对这36个关键作用靶点进行整合分析发现,补阳还五汤主要通过细胞因子与细胞因子受体的相互作用、PI3K-Akt信号通路、肿瘤坏死因子信号通路、核转录因子κB信号通路、HIF-1信号通路、NOD样受体信号通路、Jak-STAT信号通路、p53信号通路、前列腺癌等途径实现对基因表达的干预,从而治疗ED。结论:网络药理学方法揭示补阳还五汤治疗ED是多成分、多靶点、多条信号通路共同作用的结果。
基金funded by the National Natural Science Foundation of China(grant number 81874416).
文摘Objective:The objective of this study was to investigate the molecular mechanism of Buyang Huanwu decoction(BYHWD)in the treatment of diabetic foot(DF).Methods:The TCMSP,BATMAN,PubChem,PharmMapper,UniProt,GeneCards,Webgestalt,and Kobas databases were used to obtain the structures,targets,main biological functions,and pathways of the active ingredients of BYHWD,and the results were visualized using Cytoscape3.6.1,Ledock,and PyMol software.Results:A total of 82 active components of BYHWD and 193 targets related to BYHWD were identified,and 5295 genes related to DF were identified using the GeneCards database,including 65 key targets of BYHWD in the treatment of DF.GO and KEGG enrichment analyses of the 65 targets for BYHWD treatment of DF showed that 47 GO items were involved in the treatment.It was mainly involved in biological processes,such as biological regulation,metabolism,and stress response.It is primarily involved in protein binding,ion binding,nucleotide binding,and other molecular functions.It is mainly involved in membrane encapsulation,membrane lumen closure,and other biological components and involved in the VEGF,TNF,RAS,RAP1,PI3K-AKT,MAPK,and IL-17 signaling pathways.Most targets were enriched in the PI3K-AKT and MAPK signaling pathways.Molecular docking results showed that the 59 key active components of BYHWD had strong binding activity with 64 key DF targets.Conclusion:The therapeutic effect of BYHWD on DF is based on the pharmacological effects of multiple targets and pathways.
