目的:利用网络药理学及分子对接技术探讨少腹逐瘀汤治疗癌性疼痛的作用靶点及机制。方法:利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)及BATMAN-TCM...目的:利用网络药理学及分子对接技术探讨少腹逐瘀汤治疗癌性疼痛的作用靶点及机制。方法:利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)及BATMAN-TCM (a bioinformatics analysis tool for molecular mechANism of traditional Chinese medicine)数据库筛选少腹逐瘀汤化合物及有效化合物相关的靶点。利用GeneCards数据库筛选癌性疼痛相关靶点。将以上数据导入String数据库进行蛋白互作(protein-protein interaction, PPI)网络分析。利用Cytoscape构建化合物靶点网络、PPI网络。利用Bioconductor中的R包进行GO分析和KEGG分析。采用AutoDock对关键药效分子及筛选的核心靶点进行分子对接。结果:筛选出139种活性成分,药物与疾病相同靶点共有104个。GO和KEGG富集结果表明,少腹逐瘀汤可能通过调节神经元动作电位及炎症,影响MAPK信号通路和NF-kappa B信号通路从而达到抑制疼痛的作用。分子对接结果表明,少腹逐瘀汤关键化合物与CHRM2、F2R、p38 MAPK及TNF-α关键靶蛋白结合更为紧密。结论:少腹逐瘀汤对癌性疼痛的治疗是基于多组分、多靶点、多通道的综合药理作用。本研究预测了少腹逐瘀汤治疗癌性疼痛的可能机制,并为下一步深入研究提供了理论基础。展开更多
Cancer-related fatigue(CRF)is associated with cancer-related anemia(CRA).As the common comorbidities of cancer,both of them can seriously affect the quality of patient life.Yishen Qutong Granules(益肾祛痛颗粒,YSQTG)ha...Cancer-related fatigue(CRF)is associated with cancer-related anemia(CRA).As the common comorbidities of cancer,both of them can seriously affect the quality of patient life.Yishen Qutong Granules(益肾祛痛颗粒,YSQTG)have achieved good curative effects in the treatment of CRA.However,the mechanism of whether it can alleviate CRF needs further confirmation.We used network pharmacology and molecular docking to investigate the molecular mechanism and the effective compounds of the prescription.Through the analysis and research in this paper,we obtained 76 effective compounds and 76 drug-disease intersection targets to construct a network,indicating that quercetin,luteolin,baicalein,β-sitosterol and stigmasterol were possibly the most important compounds in YSQTG.The key targets of YSQTG for CRF were mainly enriched in IL-17 and TNF pathways.816 GO entries and 113 pathways were obtained by GO and KEGG enrichment,respectively,which proved that YSQTG might have a comprehensive therapeutic effect on CRF mainly through regulating IL-17,TNF,MAPK,NF-κB and chemokines,as well as cholinergic synapse and 5-HT synapse pathways.The results of molecular docking showed thatβ-sitosterol and stigmasterol could form PI-Alkyl or Alkyl hydrophobic interactions with CXCL8 and ESR1 at residues LEU25,ARG26,PHE65,ALA69 and LEU346,ALA350,LEU391,PHE404,LEU525,VAL533,respectively.In conclusion,the therapeutic effect of YSQTG on CRF is based on the comprehensive pharmacological effect of multicomponent,multitarget,and multichannel pathways.This study provides a theoretical basis for further experimental research.展开更多
文摘目的:利用网络药理学及分子对接技术探讨少腹逐瘀汤治疗癌性疼痛的作用靶点及机制。方法:利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)及BATMAN-TCM (a bioinformatics analysis tool for molecular mechANism of traditional Chinese medicine)数据库筛选少腹逐瘀汤化合物及有效化合物相关的靶点。利用GeneCards数据库筛选癌性疼痛相关靶点。将以上数据导入String数据库进行蛋白互作(protein-protein interaction, PPI)网络分析。利用Cytoscape构建化合物靶点网络、PPI网络。利用Bioconductor中的R包进行GO分析和KEGG分析。采用AutoDock对关键药效分子及筛选的核心靶点进行分子对接。结果:筛选出139种活性成分,药物与疾病相同靶点共有104个。GO和KEGG富集结果表明,少腹逐瘀汤可能通过调节神经元动作电位及炎症,影响MAPK信号通路和NF-kappa B信号通路从而达到抑制疼痛的作用。分子对接结果表明,少腹逐瘀汤关键化合物与CHRM2、F2R、p38 MAPK及TNF-α关键靶蛋白结合更为紧密。结论:少腹逐瘀汤对癌性疼痛的治疗是基于多组分、多靶点、多通道的综合药理作用。本研究预测了少腹逐瘀汤治疗癌性疼痛的可能机制,并为下一步深入研究提供了理论基础。
基金the Capital Health Development Scientific Research Project(2020-2-4026)Clinical and Translational Medicine Research Fund Projects of Cancer Hospital of Chinese Academy of Medical Science(2019XK320072)
文摘Cancer-related fatigue(CRF)is associated with cancer-related anemia(CRA).As the common comorbidities of cancer,both of them can seriously affect the quality of patient life.Yishen Qutong Granules(益肾祛痛颗粒,YSQTG)have achieved good curative effects in the treatment of CRA.However,the mechanism of whether it can alleviate CRF needs further confirmation.We used network pharmacology and molecular docking to investigate the molecular mechanism and the effective compounds of the prescription.Through the analysis and research in this paper,we obtained 76 effective compounds and 76 drug-disease intersection targets to construct a network,indicating that quercetin,luteolin,baicalein,β-sitosterol and stigmasterol were possibly the most important compounds in YSQTG.The key targets of YSQTG for CRF were mainly enriched in IL-17 and TNF pathways.816 GO entries and 113 pathways were obtained by GO and KEGG enrichment,respectively,which proved that YSQTG might have a comprehensive therapeutic effect on CRF mainly through regulating IL-17,TNF,MAPK,NF-κB and chemokines,as well as cholinergic synapse and 5-HT synapse pathways.The results of molecular docking showed thatβ-sitosterol and stigmasterol could form PI-Alkyl or Alkyl hydrophobic interactions with CXCL8 and ESR1 at residues LEU25,ARG26,PHE65,ALA69 and LEU346,ALA350,LEU391,PHE404,LEU525,VAL533,respectively.In conclusion,the therapeutic effect of YSQTG on CRF is based on the comprehensive pharmacological effect of multicomponent,multitarget,and multichannel pathways.This study provides a theoretical basis for further experimental research.
