目的 基于超高效液相色譜-四級(jí)桿飛行時(shí)間串聯(lián)質(zhì)譜法（UPLC-Q-TOF-MS/MS）分析商陸水提物的化學(xué)成分，并結(jié)合網(wǎng)絡(luò)毒理學(xué)和分子對(duì)接方法預(yù)測(cè)商陸致肝損傷的毒性成分和潛在的作用靶點(diǎn)及通路。方法 根據(jù)色譜峰保留時(shí)間、精確相對(duì)分子質(zhì)量、二級(jí)質(zhì)譜裂解碎片等信息，并結(jié)合文獻(xiàn)數(shù)據(jù)，對(duì)商陸水提物化學(xué)成分進(jìn)行分析鑒定。通過(guò)Swiss TargetPrediction、TCMSP、ETCM和BATMAN-TCM數(shù)據(jù)庫(kù)預(yù)測(cè)商陸成分靶點(diǎn)；通過(guò)CTD和GeneCards數(shù)據(jù)庫(kù)篩選肝損傷靶點(diǎn)；采用String數(shù)據(jù)庫(kù)和Cytoscape 3.7.1軟件構(gòu)建蛋白質(zhì)相互作用（PPI）網(wǎng)絡(luò)，并篩選核心靶點(diǎn)；利用Metascape數(shù)據(jù)庫(kù)對(duì)核心靶點(diǎn)進(jìn)行基因本體（GO）注釋和京都基因與基因組百科全書(shū)（KEGG）通路富集分析；應(yīng)用Cytoscape 3.7.1軟件構(gòu)建“成分-核心靶點(diǎn)-通路”網(wǎng)絡(luò)，并篩選核心成分。通過(guò)AutoDock Vina 1.2.0軟件對(duì)核心成分和核心靶點(diǎn)進(jìn)行分子對(duì)接驗(yàn)證。結(jié)果 利用UPLC-Q-TOF-MS/MS法從商陸水提物中共鑒定出40個(gè)化學(xué)成分，主要為三萜皂苷類及少量黃酮、酚酸、揮發(fā)油等。共獲得101個(gè)共有靶點(diǎn)，篩選出26個(gè)核心靶點(diǎn)，包括ALB、TNF、AKT1等；涉及通路包括HIF-1信號(hào)通路、MAPK信號(hào)通路、PI3K-Akt信號(hào)通路、TNF信號(hào)通路等，與炎癥、肝細(xì)胞凋亡、肝纖維化途徑密切相關(guān)。篩選到6個(gè)核心成分進(jìn)行分子對(duì)接，結(jié)果顯示，美商陸苷F、美商陸皂苷元、商陸皂苷A、商陸皂苷元、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與ALB、TNF、AKTI等靶點(diǎn)蛋白具有良好的結(jié)合活性。結(jié)論 商陸在大劑量使用時(shí)可能具有潛在的肝毒性，推測(cè)主要毒性成分可能為三萜皂苷類，通過(guò)促進(jìn)炎癥發(fā)生、調(diào)控肝纖維化進(jìn)程、誘導(dǎo)肝細(xì)胞凋亡途徑導(dǎo)致肝損傷。

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.

R994

國(guó)家自然科學(xué)基金資助項(xiàng)目（82173955）