基于网络药理学探讨五味消毒饮治疗盆腔炎的作用机制OA
Network pharmacology-based study on the effects and mechanisms of Wuwei Xiaodu Decoction in the treatment of pelvic inflammation in mice
目的 采用网络药理学和体外细胞实验方法探讨五味消毒饮对小鼠盆腔炎的治疗作用及其分子机制.方法 构建盆腔炎小鼠模型,通过观察小鼠体质量变化、盆腔组织形态及子宫病理学改变,评价五味消毒饮对盆腔炎小鼠的治疗作用;基于TCMSP、PubChem数据库筛选出五味消毒饮的活性成分及靶标、STRING平台构建蛋白相互作用(protein-protein interaction,PPI)网络;通过Metascape数据库对核心靶点进行GO和KEGG富集分析;使用Cytoscape软件构建成分-疾病靶点图;采用LPS诱导RAW264.7炎症细胞模型,通过Griess法检测五味消毒饮提取物对细胞一氧化氮(nitric oxide,NO)释放量的影响;Western blot 检测五味消毒饮提取物对 RAW264.7 细胞 iNOS、p-NF-κB、NF-κB、p-JNK、JNK、p-ERK、ERK蛋白水平的影响.结果 体内实验结果显示,五味消毒饮提取物能够治疗小鼠盆腔炎,改善小鼠盆腔炎模型子宫充血肿胀及与周围组织粘连的问题.经网络药理学筛选,五味消毒饮治疗盆腔炎的可能活性成分有49个,交集靶点共544个,经蛋白相互作用预测,半胱天冬酶-3(caspase-3,CASP3)、信号转导和转录激活因子3(signal transducer and activator of transcription 3,STAT3)、Src 酪氨酸蛋白激酶(SRC proto-oncogene,non-receptor tyrosine kinase,SRC)可能是五味消毒饮治疗盆腔炎的关键靶点,主要涉及糖皮质激素受体调控通路、缺氧诱导因子-1信号通路.体外实验结果显示,五味消毒饮提取物能够显著降低LPS诱导的RAW264.7细胞的NO释放量.Western blot结果表明,五味消毒饮提取物能够抑制LPS诱导的RAW264.7细胞的iNOS蛋白表达及NF-κB、MAPK信号通路中关键蛋白的活化.结论 五味消毒饮水提物和醇提物对盆腔炎小鼠炎症都有缓解效果,基于网络药理学研究,五味消毒饮具有多靶点、多通路协同作用发挥药效的特点,细胞实验表明,五味消毒饮抑制NF-κB和MAPK信号途径异常激活.
Objective To employ the network pharmacology approach and in vitro cell experiments to investigate the thera-peutic effects and molecular mechanisms of Wuwei Xiaodu Decoction in the treatment of pelvic inflammatory disease in mice.Methods Firstly,a mouse model of pelvic inflammatory disease was constructed,and the therapeutic effect of Wuwei Xiaodu Decoction on pelvic inflammatory disease mice was evaluated through weight changes,morphological examination of pelvic tis-sues,and pathological observation of uterine tissues as evaluation indicators;TCMSP and Pubchem databases were used to screen out the active ingredients and targets of Wuwei Xiaodu Decoction,and the STRING platform was used to construct a protein-pro-tein interaction(PPI)network;the Metascape database was used to perform GO and KEGG enrichment analysis on core targets;the Cytoscape software was used to construct a component disease target map;the LPS was used to induce RAW264.7 inflamma-tory cell model,and the effect of Wuwei Xiaodu Decoction on the secretion of nitric oxide(NO)in cells was detected by Griess method;the Western blot was used to detect the effects of Wuwei Xiaodu Decoction extract on iNOS,p-NF-κB、NF-κB,p-JNK、JNK,p-ERK and ERK protein levels in RAW264.7 cells.Results In vivo,Wuwei Xiaodu Decoction could be used to improve uterine congestion,swelling,and adhesion to surrounding tissues in the mouse pelvic inflammatory disease model.Through net-work pharmacology screening,there were 49 potential active ingredients and 544 intersecting targets in Wuwei Xiaodu Decoction for treating pelvic inflammatory disease.Protein interaction prediction suggested that caspase-3,STAT3,and SRC might be key targets for Wuwei Xiaodu Decoction in treating pelvic inflammatory disease,mainly involving the glucocorticoid receptor regulato-ry pathway and hypoxia inducible factor-1 signaling pathway.In vitro,Wuwei Xiaodu Decoction significantly reduced the secre-tion of NO in RAW264.7 cells induced by LPS.Wuwei Xiaodu Decoction could inhibit the expression of iNOS protein and the activation of key proteins in the NF-κB and MAPK signaling pathways induced by LPS in RAW264.7 cells.Conclusion Wuwei Xiaodu Decoction has a relieving effect on pelvic inflammatory disease in mice.Based on network pharmacology research,Wuwei Xiaodu Decoction has the characteristics of multi-target and multi pathway synergistic effects to exert its therapeutic effects.Cell experiments show that Wuwei Xiaodu Decoction inhibits abnormal pathway activation of NF-κB and MAPK signaling pathways.
邵婉君;荣小倩;徐汝飛;于聪颖;杨爱琳
山东医药大学 山东烟台 264003山东医药大学 山东烟台 264003山东医药大学 山东烟台 264003山东医药大学 山东烟台 264003山东医药大学 山东烟台 264003
医药卫生
五味消毒饮盆腔炎网络药理学
Wuwei Xiaodu Decoctionpelvic infectionnetwork pharmacology
《滨州医学院学报》 2026 (3)
296-303,8
山东省高等学校"青创团队计划"(2024KJJ007)滨州医学院高层次人才引进计划(BY2020KYQD13)国家中医药管理局科技司科技共建项目(GZY-KJS-SD-2024-049)
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