目的 基于超高效液相色谱-四级杆飞行时间串联质谱法（UPLC-Q-TOF-MS/MS）分析商陆水提物的化学成分，并结合网络毒理学和分子对接方法预测商陆致肝损伤的毒性成分和潜在的作用靶点及通路。方法 根据色谱峰保留时间、精确相对分子质量、二级质谱裂解碎片等信息，并结合文献数据，对商陆水提物化学成分进行分析鉴定。通过Swiss TargetPrediction、TCMSP、ETCM和BATMAN-TCM数据库预测商陆成分靶点；通过CTD和GeneCards数据库筛选肝损伤靶点；采用String数据库和Cytoscape 3.7.1软件构建蛋白质相互作用（PPI）网络，并筛选核心靶点；利用Metascape数据库对核心靶点进行基因本体（GO）注释和京都基因与基因组百科全书（KEGG）通路富集分析；应用Cytoscape 3.7.1软件构建“成分-核心靶点-通路”网络，并筛选核心成分。通过AutoDock Vina 1.2.0软件对核心成分和核心靶点进行分子对接验证。结果 利用UPLC-Q-TOF-MS/MS法从商陆水提物中共鉴定出40个化学成分，主要为三萜皂苷类及少量黄酮、酚酸、挥发油等。共获得101个共有靶点，筛选出26个核心靶点，包括ALB、TNF、AKT1等；涉及通路包括HIF-1信号通路、MAPK信号通路、PI3K-Akt信号通路、TNF信号通路等，与炎症、肝细胞凋亡、肝纤维化途径密切相关。筛选到6个核心成分进行分子对接，结果显示，美商陆苷F、美商陆皂苷元、商陆皂苷A、商陆皂苷元、山柰酚3-O-α-L-鼠李吡喃糖基（1→2）-β-D-吡喃葡萄糖苷及芥子酸与ALB、TNF、AKTI等靶点蛋白具有良好的结合活性。结论 商陆在大剂量使用时可能具有潜在的肝毒性，推测主要毒性成分可能为三萜皂苷类，通过促进炎症发生、调控肝纤维化进程、诱导肝细胞凋亡途径导致肝损伤。

Objective To analyze the chemical components of Phytolaccae Radix based on ultra performance liquid chromatographyquadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS). And to predict the toxic components, potential targets and pathways of liver injury induced by Phytolaccae Radix based on network toxicology and molecular docking. Methods According to the retention time of chromatographic peak, accurate molecular weight and fragmentation information of secondary mass spectrometry, combined with the literature data, the chemical components of Phytolaccae Radix were analyzed and identified. The component targets of Phytolaccae Radix were predict by Swiss Target Prediction, TCMSP, ETCM and BATMAN-TCM Database. The liver injury targets were screened by CTD and GeneCards databases. By using String database and Cytoscape 3.7.1 software, PPI network was constructed and core targets were screened. By using Metascape database, Gene Ontology (GO) annotation and KEGG pathway enrichment were analyzed of core targets. Cytoscape 3.7.1 software was used to construct the "component-core target-pathway" network and screen the core components. The molecular docking verification of core components and core targets was performed by AutoDock Vina 1.2.0 software. Results A total of 40 chemical components were identified from the aqueous extract of Phytolaccae Radix, mainly triterpenoid saponins, and a small amount of flavonoids, phenolic acids, volatile oil. A total of 101 common targets were obtained, and 26 core targets were screened, including ALB, TNF, AKT1, etc. The pathways involved include HIF-1 signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway, TNF signaling pathway and so on, which are closely related to inflammation, hepatocyte apoptosis and hepatic fibrosis. Six core components were screened for molecular docking. The results showed that phytolaccoside F, phytolaccagenin, esculentoside A, esculentagenin, kaempferol 3-O-alpha-L-rhamnopyranosyl (1→2)-beta-D-glucopyranoside and sinapic acid had good binding activities with ALB, TNF, AKT1 and other target proteins. Conclusion Phytolaccae Radix may have potential hepatotoxicity when used in large doses. It is speculated that the main toxic components may be triterpenoid saponins, which play a role in liver injury by promoting inflammation, regulating liver fibrosis, and inducing hepatocyte apoptosis.

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国家自然科学基金资助项目（82173955）