目的:探究加味香薷口服液治疗腹泻疾病的潜在机制。方法:通过网络药理学和分子对接技术预测加味香薷口服液抗腹泻的主要活性成分、靶点及信号通路,并对预测的结果进行体外实验验证。结果:网络药理学结果表明,加味香薷口服液通过槲皮素...目的:探究加味香薷口服液治疗腹泻疾病的潜在机制。方法:通过网络药理学和分子对接技术预测加味香薷口服液抗腹泻的主要活性成分、靶点及信号通路,并对预测的结果进行体外实验验证。结果:网络药理学结果表明,加味香薷口服液通过槲皮素、木犀草素、大豆苷元等黄酮类化合物及β-谷甾醇、β-胡萝卜素作用于丝/苏氨酸蛋白激酶1(serine/threonine protein kinase 1,AKT1)、信号传导和转录激活因子3(signal transducer and activator of transcription 3,STAT3)、白细胞介素-6等核心靶蛋白密切参与腹泻症状的发展进程;依据分子对接数据,其关键化合物与核心靶蛋白间结合能力普遍较强;脂多糖诱导的IEC-6肠上皮细胞实验表明,与模型组相比,加味香薷口服液能提高细胞存活率(P<0.05),使炎症因子白细胞介素-1β、肿瘤坏死因子-α和白细胞介素-6分泌水平降低(P<0.05),白细胞介素-10水平上升(P<0.01),并与剂量呈依赖趋势;还能下调磷酸化AKT1、肿瘤蛋白p53和磷酸化传导及转录激活因子3蛋白表达(P<0.05),上调表皮生长因子受体蛋白表达(P<0.05)。结论:加味香薷口服液主要通过多靶点、多信号通路以有效缓解脂多糖诱导的腹泻,其机制可能与STAT3、AKT1等关联信号通路的持续激活、调控肠道炎症状态、细胞应激反应有关。展开更多
法尼酯X受体(farnesoid X receptor,FXR)是核受体超家族成员,主要在肝脏和小肠中表达并由胆汁酸激活。靶向FXR已成为治疗多种代谢性疾病的有效方法,然而目前已开发的FXR激动剂在结构和疗效上仍存在一定缺陷。前期研究发现,新型FXR激动...法尼酯X受体(farnesoid X receptor,FXR)是核受体超家族成员,主要在肝脏和小肠中表达并由胆汁酸激活。靶向FXR已成为治疗多种代谢性疾病的有效方法,然而目前已开发的FXR激动剂在结构和疗效上仍存在一定缺陷。前期研究发现,新型FXR激动剂主要包括异噁唑类、磺胺类、萜类等化合物。这些新型FXR激动剂主要在调节脂质和胆汁酸代谢、抗炎、抗纤维化、对抗氧化应激等方面发挥重要作用,且部分新型FXR激动剂已进入临床研究阶段,具有良好的应用前景。该文对近几年新型FXR激动剂的结构改进、药理机制及应用前景作一综述,以期为以FXR为靶点的激动剂开发与应用提供思路。展开更多
To elucidate the mechanisms underlying the therapeutic effects of the herbal medicine pair Smilax Glabra and Semen Coicis in treating gout and hyperuricemia,a comprehensive analysis was conducted using network pharmac...To elucidate the mechanisms underlying the therapeutic effects of the herbal medicine pair Smilax Glabra and Semen Coicis in treating gout and hyperuricemia,a comprehensive analysis was conducted using network pharmacology and molecular docking methods.Disease-associated targets for gout and hyperuricemia were identified from the GeneCards,OMIM,Disgenet,and TTD databases,while the key active components and their corresponding targets for Smilax Glabra and Semen Coicis were obtained from the TCSMP database.The intersection of these targets enabled the construction of a protein-protein interaction(PPI)network,which was subsequently visualized and analyzed.Core targets were further subjected to Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses to elucidate the biological processes and pathways involved.Molecular docking was then employed to validate the reliability of the interactions between the active components and the identified targets.The analysis revealed that Smilax Glabra and Semen Coicis contained 15 bioactive components that interacted with 393 potential targets,while gout and hyperuricemia were associated with 660 targets in total.The primary active compounds implicated in treating these conditions included diosgenin,quercetin,and naringenin,which were found to interact with crucial hub targets such as BCL2,CASP3,and MAPK3.These interactions suggested that the herbal medicine pair modulated several biological processes,including gland development and the regulation of body fluid levels,through pathways involving membrane rafts,membrane microdomains,and nuclear receptor activities.Enrichment analyses highlighted their involvement in multiple signaling pathways,such as EGFR tyrosine kinase inhibitor resistance,phospholipase D signaling,and platelet activation.Molecular docking confirmed the strong binding affinities between the hub genes and the major active components,supporting their potential role in therapeutic efficacy.This study demonstrated that Smilax Glabra and Semen Coicis might offer a promising therapeutic strategy for gout and hyperuricemia by targeting multiple molecular components,biological functions,and pathways.The findings underscored the unique potential of traditional Chinese medicine(TCM)in managing complex diseases by leveraging synergistic effects across diverse biological mechanisms.展开更多
Euphorbia helioscopia,a natural plant recognized for its anti-tumor properties,has been extensively investigated in various cancers.However,its therapeutic potential in gastric cancer with positive lymph node metastas...Euphorbia helioscopia,a natural plant recognized for its anti-tumor properties,has been extensively investigated in various cancers.However,its therapeutic potential in gastric cancer with positive lymph node metastasis remains underexplored.This study aimed to elucidate the role of E.helioscopia in treating gastric cancer with lymph node metastasis using an integrative approach that combined network pharmacology,molecular docking,and molecular dynamics simulations.Initially,shared target data between E.helioscopia and gastric cancer with positive lymph node metastasis were identified and systematically analyzed.Subsequently,molecular docking was conducted to validate the interactions between key components and targets.Finally,molecular dynamics simulations were employed,with binding free energy calculations performed using the MM-PBSA algorithm.The findings revealed that the primary bioactive compounds of E.helioscopia in this context included quercetin and luteolin,targeting core molecules such as EGFR and MMP9.Key pathways implicated in its mechanism of action included resistance to EGFR tyrosine kinase inhibitors,among others.Molecular docking demonstrated robust binding affinity between the active compounds and critical targets,with molecular dynamics and binding free energy analyses highlighting a particularly stable interaction between luteolin and MMP9.In conclusion,E.helioscopia exhibited a multi-component,multi-target,and multi-pathway therapeutic profile in treating gastric cancer with positive lymph node metastasis.These findings offered valuable theoretical insights supporting its potential clinical application in oncology.展开更多
文摘目的:探究加味香薷口服液治疗腹泻疾病的潜在机制。方法:通过网络药理学和分子对接技术预测加味香薷口服液抗腹泻的主要活性成分、靶点及信号通路,并对预测的结果进行体外实验验证。结果:网络药理学结果表明,加味香薷口服液通过槲皮素、木犀草素、大豆苷元等黄酮类化合物及β-谷甾醇、β-胡萝卜素作用于丝/苏氨酸蛋白激酶1(serine/threonine protein kinase 1,AKT1)、信号传导和转录激活因子3(signal transducer and activator of transcription 3,STAT3)、白细胞介素-6等核心靶蛋白密切参与腹泻症状的发展进程;依据分子对接数据,其关键化合物与核心靶蛋白间结合能力普遍较强;脂多糖诱导的IEC-6肠上皮细胞实验表明,与模型组相比,加味香薷口服液能提高细胞存活率(P<0.05),使炎症因子白细胞介素-1β、肿瘤坏死因子-α和白细胞介素-6分泌水平降低(P<0.05),白细胞介素-10水平上升(P<0.01),并与剂量呈依赖趋势;还能下调磷酸化AKT1、肿瘤蛋白p53和磷酸化传导及转录激活因子3蛋白表达(P<0.05),上调表皮生长因子受体蛋白表达(P<0.05)。结论:加味香薷口服液主要通过多靶点、多信号通路以有效缓解脂多糖诱导的腹泻,其机制可能与STAT3、AKT1等关联信号通路的持续激活、调控肠道炎症状态、细胞应激反应有关。
文摘法尼酯X受体(farnesoid X receptor,FXR)是核受体超家族成员,主要在肝脏和小肠中表达并由胆汁酸激活。靶向FXR已成为治疗多种代谢性疾病的有效方法,然而目前已开发的FXR激动剂在结构和疗效上仍存在一定缺陷。前期研究发现,新型FXR激动剂主要包括异噁唑类、磺胺类、萜类等化合物。这些新型FXR激动剂主要在调节脂质和胆汁酸代谢、抗炎、抗纤维化、对抗氧化应激等方面发挥重要作用,且部分新型FXR激动剂已进入临床研究阶段,具有良好的应用前景。该文对近几年新型FXR激动剂的结构改进、药理机制及应用前景作一综述,以期为以FXR为靶点的激动剂开发与应用提供思路。
文摘To elucidate the mechanisms underlying the therapeutic effects of the herbal medicine pair Smilax Glabra and Semen Coicis in treating gout and hyperuricemia,a comprehensive analysis was conducted using network pharmacology and molecular docking methods.Disease-associated targets for gout and hyperuricemia were identified from the GeneCards,OMIM,Disgenet,and TTD databases,while the key active components and their corresponding targets for Smilax Glabra and Semen Coicis were obtained from the TCSMP database.The intersection of these targets enabled the construction of a protein-protein interaction(PPI)network,which was subsequently visualized and analyzed.Core targets were further subjected to Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses to elucidate the biological processes and pathways involved.Molecular docking was then employed to validate the reliability of the interactions between the active components and the identified targets.The analysis revealed that Smilax Glabra and Semen Coicis contained 15 bioactive components that interacted with 393 potential targets,while gout and hyperuricemia were associated with 660 targets in total.The primary active compounds implicated in treating these conditions included diosgenin,quercetin,and naringenin,which were found to interact with crucial hub targets such as BCL2,CASP3,and MAPK3.These interactions suggested that the herbal medicine pair modulated several biological processes,including gland development and the regulation of body fluid levels,through pathways involving membrane rafts,membrane microdomains,and nuclear receptor activities.Enrichment analyses highlighted their involvement in multiple signaling pathways,such as EGFR tyrosine kinase inhibitor resistance,phospholipase D signaling,and platelet activation.Molecular docking confirmed the strong binding affinities between the hub genes and the major active components,supporting their potential role in therapeutic efficacy.This study demonstrated that Smilax Glabra and Semen Coicis might offer a promising therapeutic strategy for gout and hyperuricemia by targeting multiple molecular components,biological functions,and pathways.The findings underscored the unique potential of traditional Chinese medicine(TCM)in managing complex diseases by leveraging synergistic effects across diverse biological mechanisms.
基金The Gansu Province University Industrial Support Plan(Grant No.2023CYZC-05)the Cuiying Technology Innovation Project of Lanzhou University Second Hospital(Grant No.CY2022-MS-B04)+1 种基金the Doctoral Students Training Research Fund of Lanzhou University Second Hospital(Grant No.YJS-BD-32)the Gansu Province Drug Regulatory Science Research Project in 2024(Grant No.2024GSMPA032).
文摘Euphorbia helioscopia,a natural plant recognized for its anti-tumor properties,has been extensively investigated in various cancers.However,its therapeutic potential in gastric cancer with positive lymph node metastasis remains underexplored.This study aimed to elucidate the role of E.helioscopia in treating gastric cancer with lymph node metastasis using an integrative approach that combined network pharmacology,molecular docking,and molecular dynamics simulations.Initially,shared target data between E.helioscopia and gastric cancer with positive lymph node metastasis were identified and systematically analyzed.Subsequently,molecular docking was conducted to validate the interactions between key components and targets.Finally,molecular dynamics simulations were employed,with binding free energy calculations performed using the MM-PBSA algorithm.The findings revealed that the primary bioactive compounds of E.helioscopia in this context included quercetin and luteolin,targeting core molecules such as EGFR and MMP9.Key pathways implicated in its mechanism of action included resistance to EGFR tyrosine kinase inhibitors,among others.Molecular docking demonstrated robust binding affinity between the active compounds and critical targets,with molecular dynamics and binding free energy analyses highlighting a particularly stable interaction between luteolin and MMP9.In conclusion,E.helioscopia exhibited a multi-component,multi-target,and multi-pathway therapeutic profile in treating gastric cancer with positive lymph node metastasis.These findings offered valuable theoretical insights supporting its potential clinical application in oncology.
