目的 基于超高效液相色谱-四极杆/静电场轨道阱高分辨质谱（UHPLC-Q-Orbitrap HRMS）与网络药理学方法系统解析芪萆饮的化学成分及其体内入血特征，并从分子网络层面探讨其治疗前列腺癌的潜在作用机制。方法 采用UHPLC-Q-Orbitrap HRMS鉴定芪萆饮化学成分并解析入血特征，结合多数据库靶标预测与前列腺癌多队列转录组数据，通过差异分析、WGCNA、蛋白相互作用（PPI）网络及基因本体（GO）/京都基因和基因组百科全书（KEGG）富集分析系统探讨其潜在作用机制。采用分子对接方法验证主要活性成分与核心靶标之间的结合特征。结果 共鉴定出生物碱类、酚酸类、黄酮及异黄酮类、皂苷类等81种化合物，其中49种以原型形式入血，未观察到明显的相Ⅰ或相Ⅱ代谢产物信号，提示芪萆饮关键成分具有良好的体内暴露基础。网络药理学分析共筛选出89个可能介导芪萆饮治疗前列腺癌的关键潜在靶标。GO富集结果显示，这些靶标主要参与细胞黏附调控、生物刺激应答及凝血相关过程，并显著定位于黏着斑、细胞-基质连接位点等结构；KEGG通路分析表明其显著富集于磷酸肌醇3-激酶（PI3K）/蛋白激酶B（Akt）、丝裂原活化蛋白激酶（MAPK）、Rap1、血管内皮生长因子（VEGF）及钙信号通路等癌症相关通路。分子对接结果显示整合素α5（ITGA5）与多种入血活性成分（如黄芪皂苷IV、王不留行环肽A）表现出较强结合能力，而ErbB3受体酪氨酸激酶（ERBB3）直接结合能力较弱。结论 芪萆饮可能通过调控细胞外基质-整合素介导的黏着斑信号，联动多条经典致癌及微环境相关通路，对前列腺癌发生发展实施多靶点、多层级的整体干预作用。

Objective To characterize the chemical constituents and in vivo absorbed components of Qibi Decoction by using UHPLC-Q-Orbitrap HRMS, and to explore its potential mechanisms against prostate cancer through network pharmacology. Methods Chemical constituents and absorbed components of Qibi Decoction were identified by UHPLC-Q-Orbitrap HRMS. Potential targets were predicted using multiple databases and integrated with multi-cohort prostate cancer transcriptomic data. Differential expression analysis, WGCNA, PPI network construction, and GO/KEGG enrichment analyses were performed to investigate the underlying mechanisms. Molecular docking was conducted to evaluate the binding characteristics between major active components and core targets. Molecular docking was employed to validate the binding characteristics between major active components and core targets. Results Eighty-one compounds were identified, including alkaloids, phenolic acids, flavonoids/isoflavonoids, and saponins, among which 49 prototype compounds were detected in plasma. No evident phase I or phase II metabolites were observed, indicating favorable in vivo exposure of key components. Network pharmacology analysis identified 89 potential targets associated with the anti prostate cancer effects of Qibi Decoction, which were mainly involved in cell adhesion regulation and enriched in cancer-related pathways, including PI3K/Akt, MAPK, Rap1, VEGF, and calcium signaling. Molecular docking revealed strong binding affinities between ITGA5 and several absorbed active components (astragaloside IV, vaccariae cyclopeptide A), whereas ERBB3 showed relatively weak direct binding capacity. Conclusion Qibi Decoction may exert multi-target and multi-level therapeutic effects on prostate cancer by modulating extracellular matrix integrin mediated focal adhesion signaling and multiple oncogenic pathways.

R287.3

天津市教育委员会项目（2022KJ174）；天津市卫健委项目（2025050）