Objective:To examine the therapeutic effect of Fangji Fuling Decoction(FFD) on sepsis through network pharmacological analysis combined with in vitro and in vivo experiments.Methods:A sepsis mouse model was constructe...Objective:To examine the therapeutic effect of Fangji Fuling Decoction(FFD) on sepsis through network pharmacological analysis combined with in vitro and in vivo experiments.Methods:A sepsis mouse model was constructed through intraperitoneal injection of 20 mg/kg lipopolysaccharide(LPS).RAW264.7 cells were stimulated by 250 ng/m L LPS to establish an in vitro cell model.Network pharmacology analysis identified the key molecular pathway associated with FFD in sepsis.Through ectopic expression and depletion experiments,the effect of FFD on multiple organ damage in septic mice,as well as on cell proliferation and apoptosis in relation to the mitogen-activated protein kinase 14/Forkhead Box O 3A(MAPK14/FOXO3A) signaling pathway,was analyzed.Results:FFD reduced organ damage and inflammation in LPS-induced septic mice and suppressed LPS-induced macrophage apoptosis and inflammation in vitro(P<0.05).Network pharmacology analysis showed that FFD could regulate the MAPK14/FOXO signaling pathway during sepsis.As confirmed by in vitro cell experiments,FFD inhibited the MAPK14 signaling pathway or FOXO3A expression to relieve LPS-induced macrophage apoptosis and inflammation(P<0.05).Furthermore,FFD inhibited the MAPK14/FOXO3A signaling pathway to inhibit LPS-induced macrophage apoptosis in the lung tissue of septic mice(P<0.05).Conclusion:FFD could ameliorate the LPS-induced inflammatory response in septic mice by inhibiting the MAPK14/FOXO3A signaling pathway.展开更多
目的运用计算机网络药理学技术预测桃核承气汤治疗脓毒症心肌功能障碍的作用靶点和信号通路,进一步分析其防治脓毒症心肌功能障碍的基础和作用机制。方法运用中药系统药理学成分分析平台Traditional Chinese Medicine Systems Pharmacol...目的运用计算机网络药理学技术预测桃核承气汤治疗脓毒症心肌功能障碍的作用靶点和信号通路,进一步分析其防治脓毒症心肌功能障碍的基础和作用机制。方法运用中药系统药理学成分分析平台Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP)数据库获取桃核承气汤的有效成分及作用靶标基因,从GeneCards数据库收集脓毒症心肌功能障碍的靶标基因,将两者取交集后得到疾病-药物蛋白靶基因,运用STRING构建蛋白质间相互作用网络,并通过Cytoscape软件将结果进行网络可视化展示,通过网络结构和节点间加权重联系的计算分析算法筛选出作用的关键基因。借助Webgestalt在线工具进行疾病-药物交集靶基因的基因本体论(GO)分析和京都基因与基因组百科全书(KEGG)通路富集分析,并可视化展示。最后利用CTD数据库并结合文献学习,获取关键基因于脓毒症心肌功能障碍的疾病治疗作用。结果桃核承气汤的135个化合物中有64成分通过20个靶点与脓毒症心肌功能障碍相互关联。其中AKT1、HMOX1、JUN、TNF、IL1B、MAPK14、NOS3、PPARG、ICAM1、NOS2、VCAM1、STAT1等关键基因主要通过调控炎症反应、促进细胞存活、抗细胞凋亡、参与能量代谢、病原识别、毒物代谢等路径,在质膜、细胞膜、吞噬细胞、线粒体自噬等分子反应中发挥作用。结论网络药理学方法科学预测桃核承气汤防治脓毒症心肌功能障碍的关键靶标及其参与的相关通路,提示该方剂对脓毒症心肌功能障碍的防治作用为多靶点、多通路、多选择的复杂机制,并且多与抗炎、抗细胞凋亡、促进细胞存活等机制相关。展开更多
文摘Objective:To examine the therapeutic effect of Fangji Fuling Decoction(FFD) on sepsis through network pharmacological analysis combined with in vitro and in vivo experiments.Methods:A sepsis mouse model was constructed through intraperitoneal injection of 20 mg/kg lipopolysaccharide(LPS).RAW264.7 cells were stimulated by 250 ng/m L LPS to establish an in vitro cell model.Network pharmacology analysis identified the key molecular pathway associated with FFD in sepsis.Through ectopic expression and depletion experiments,the effect of FFD on multiple organ damage in septic mice,as well as on cell proliferation and apoptosis in relation to the mitogen-activated protein kinase 14/Forkhead Box O 3A(MAPK14/FOXO3A) signaling pathway,was analyzed.Results:FFD reduced organ damage and inflammation in LPS-induced septic mice and suppressed LPS-induced macrophage apoptosis and inflammation in vitro(P<0.05).Network pharmacology analysis showed that FFD could regulate the MAPK14/FOXO signaling pathway during sepsis.As confirmed by in vitro cell experiments,FFD inhibited the MAPK14 signaling pathway or FOXO3A expression to relieve LPS-induced macrophage apoptosis and inflammation(P<0.05).Furthermore,FFD inhibited the MAPK14/FOXO3A signaling pathway to inhibit LPS-induced macrophage apoptosis in the lung tissue of septic mice(P<0.05).Conclusion:FFD could ameliorate the LPS-induced inflammatory response in septic mice by inhibiting the MAPK14/FOXO3A signaling pathway.
文摘目的运用计算机网络药理学技术预测桃核承气汤治疗脓毒症心肌功能障碍的作用靶点和信号通路,进一步分析其防治脓毒症心肌功能障碍的基础和作用机制。方法运用中药系统药理学成分分析平台Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP)数据库获取桃核承气汤的有效成分及作用靶标基因,从GeneCards数据库收集脓毒症心肌功能障碍的靶标基因,将两者取交集后得到疾病-药物蛋白靶基因,运用STRING构建蛋白质间相互作用网络,并通过Cytoscape软件将结果进行网络可视化展示,通过网络结构和节点间加权重联系的计算分析算法筛选出作用的关键基因。借助Webgestalt在线工具进行疾病-药物交集靶基因的基因本体论(GO)分析和京都基因与基因组百科全书(KEGG)通路富集分析,并可视化展示。最后利用CTD数据库并结合文献学习,获取关键基因于脓毒症心肌功能障碍的疾病治疗作用。结果桃核承气汤的135个化合物中有64成分通过20个靶点与脓毒症心肌功能障碍相互关联。其中AKT1、HMOX1、JUN、TNF、IL1B、MAPK14、NOS3、PPARG、ICAM1、NOS2、VCAM1、STAT1等关键基因主要通过调控炎症反应、促进细胞存活、抗细胞凋亡、参与能量代谢、病原识别、毒物代谢等路径,在质膜、细胞膜、吞噬细胞、线粒体自噬等分子反应中发挥作用。结论网络药理学方法科学预测桃核承气汤防治脓毒症心肌功能障碍的关键靶标及其参与的相关通路,提示该方剂对脓毒症心肌功能障碍的防治作用为多靶点、多通路、多选择的复杂机制,并且多与抗炎、抗细胞凋亡、促进细胞存活等机制相关。
