摘要
目的通过动物模型观察麦冬各部位提取物止咳化痰作用,并结合网络药理学与分子对接技术探讨其作用机制。方法分离制备麦冬总提取物、总黄酮、总多糖及总皂苷部位。采用氨水引咳小鼠模型观察各提取物(120 mg·kg^(-1))止咳活性(咳嗽次数及咳嗽潜伏期);气管酚红排泄实验检测祛痰效果。结合网络药理学分析:1)通过公共数据库(BATMAN-TCM等)和Swiss-ADME药动学参数筛选确定麦冬化学成分;2)使用SwissTargetPrediction预测潜在靶点;3)从GeneCards、OMIM等数据库中收集疾病靶点(“咳嗽”/“咳痰”)。通过基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析确定关键通路,并利用AutoDock Vina分子对接验证关键靶点。结果与对照组比较,麦冬各部位提取物显著减少咳嗽次数、延长咳嗽潜伏期,增加酚红排泌量(P<0.001)。网络药理学筛选出122个活性成分和384个作用靶点,其中80个与止咳祛痰相关。通路富集显示PI3K/Akt/mTOR为潜在核心信号通路,HSP90AB1和BRAF可能为关键调控靶点。结论首次整合动物实验、网络药理学和分子对接技术,揭示麦冬止咳化痰的多组分协同作用,其机制可能涉及PI3K/Akt/mTOR通路调控。
Objective To investigate the antitussive and expectorant effects of Ophiopogon japonicus extracts using animal models,and to elucidate the mechanism of action through an integrated approach combining network pharmacology and molecular docking.Methods Total extracts and bioactive fractions(flavonoids,polysaccharides,saponins)were isolated from O.japonicus.Antitussive activity was evaluated via ammonia-induced cough model(quantifying cough frequency and latency),while expectorant efficacy was assessed through tracheal phenol red excretion.Network pharmacology analysis was performed by:1)Identifying O.japonicus chemical constituents through public databases(BATMAN-TCM)and Swiss-ADME pharmacokinetic screening;2)Predicting potential targets using SwissTargetPrediction;3)Collecting disease targets(cough/expectoration)from databases GeneCards and OMIM.Key pathways were identified through GO/KEGG enrichment analysis,with critical targets validated by AutoDock Vina molecular docking.Results The extracts of all parts of O.japonicus significantly reduced the number of coughs,prolonged the latency period,and increased phenol red excretion.Network pharmacological screening identified 122 active ingredients and 384 targets.Of note,80 targets were identified as being associated with cough and expectorant properties.Pathway enrichment analysis identified the PI3K/Akt/mTOR signaling pathway as a potentially key regulator,with HSP90AB1 and BRAF as significant targets for regulation.Conclusion The animal experiments were integrated with network pharmacology and molecular docking techniques to elucidate the multicomponent synergistic effects of O.japonicus in alleviating cough and promoting expectoration.The underlying mechanism may involve regulating the PI3K/Akt/mTOR pathway.
作者
张沛沛
崔名杨
郑永哲
申玥
才谦
曾克武
屠鹏飞
ZHANG Peipei;CUI Mingyang;ZHENG Yongzhe;SHEN Yue;CAI Qian;ZENG Kewu;TU Pengfei(State Key Laboratory of Natural and Biomimetic Drugs,School of Pharmaceutical Sciences,Peking University,Beijing 100191,China;School of Chinese Medicine,China Pharmaceutical University,Nanjing 211198,China;School of Chinese Medicine,Liaoning University of Traditional Chinese Medicine,Shenyang 116600,China)
出处
《药物评价研究》
北大核心
2025年第11期3151-3163,共13页
Drug Evaluation Research
基金
四川省中医药科技产业创新团队专项课题项目(2022C002)。
关键词
麦冬
止咳化痰
药效物质
分子对接
分子机制
PI3K/Akt/mTOR通路
Ophiopogon japonicas(L.f)Ker-Gawl.
antitussive and expectorant effect
active substance
molecular docking
molecular mechanism
PI3K/Akt/mTOR pathway
