目的 采用超高效液相色譜-四極桿靜電場(chǎng)軌道阱質(zhì)譜（UPLC-Orbitrap-MS/MS）技術(shù)對(duì)巴戟天化學(xué)成分快速分析，并開(kāi)展環(huán)烯醚萜類成分抗類風(fēng)濕性關(guān)節(jié)炎（RA）的網(wǎng)絡(luò)藥理學(xué)研究。方法 運(yùn)用UPLC-Orbitrap-MS/MS技術(shù)在正、負(fù)離子模式下分別對(duì)巴戟天中化學(xué)成分進(jìn)行定性分析，利用UPLC-MS/MS技術(shù)、proteowizard和XCMS軟件、輔助應(yīng)用公共數(shù)據(jù)庫(kù)和自建中藥物質(zhì)庫(kù)，表征巴戟天化學(xué)成分。利用網(wǎng)絡(luò)靶點(diǎn)數(shù)據(jù)庫(kù)獲取已鑒定到的環(huán)烯醚萜類成分的作用靶點(diǎn)和RA相關(guān)疾病靶點(diǎn)信息；采用DAVID數(shù)據(jù)庫(kù)對(duì)核心靶點(diǎn)進(jìn)行基因本體（GO）和京都基因與基因組百科全書(shū)（KEGG）富集分析；借助GeneMANIA平臺(tái)繪制交集蛋白質(zhì)-蛋白質(zhì)相互作用（PPI）網(wǎng)絡(luò)篩選關(guān)鍵靶點(diǎn)；利用分子對(duì)接技術(shù)聚焦環(huán)烯醚萜類成分作用靶標(biāo)。結(jié)果 利用UPLC-Orbitrap-MS/MS技術(shù)共鑒定出巴戟天中的370個(gè)化學(xué)成分，共檢測(cè)出環(huán)烯醚萜類物質(zhì)4個(gè)；篩選了4個(gè)環(huán)烯醚萜類物質(zhì)的藥效作用靶點(diǎn)318個(gè)，RA疾病靶點(diǎn)1 001個(gè)，交集靶點(diǎn)69個(gè)。GO 478條和KEGG富集到相關(guān)通路137條，最終確定環(huán)烯醚萜類成分可能通過(guò)腫瘤壞死因子α（TNF-α）、Janus激酶2（JAK2）、信號(hào)傳導(dǎo)及轉(zhuǎn)錄激活蛋白3（SATA3）和蛋白酪氨酸磷酸酶受體C（PTPRC）關(guān)鍵靶點(diǎn)，協(xié)同調(diào)控TNF-α、磷脂酰肌醇3激酶（PI3K）-蘇氨酸激酶（Akt）和JAK-STAT等信號(hào)通路發(fā)揮抗RA的治療作用。分子對(duì)接得分顯示水晶蘭苷與關(guān)鍵靶點(diǎn)較好地結(jié)合。結(jié)論 巴戟天中的環(huán)烯醚萜類成分可能通過(guò)干預(yù)TNF、JAK2、SATA3和PTPRC靶點(diǎn)，調(diào)控PI3K-Akt和JAK-STAT等信號(hào)通路發(fā)揮抗RA的治療作用。

Objective To rapidly analyze the chemical constituents of Morinda officinalis using ultra-performance liquid chromatography coupled with quadrupole-orbitrap tandem mass spectrometry (UPLC-Orbitrap-MS/MS) and to investigate the antirheumatoid arthritis (RA) effects of its iridoid glycosides through network pharmacology.Methods Qualitative analysis of the chemical constituents in M. officinalis was conducted using UPLC-Orbitrap-MS/MS technology in both positive and negative ion modes. The characterization of chemical components was achieved through the application of UPLC-MS/MS technology, complemented by ProteoWizard and XCMS software platforms, with additional support from public databases and a proprietary traditional Chinese medicine substance library. Network target databases were systematically utilized to identify the target proteins of the detected iridoid components and the disease targets associated with RA. The DAVID database was employed for Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the core targets. The GeneMANIA platform was used to construct a protein-protein interaction (PPI) network of overlapping targets to screen key targets. Molecular docking technology was applied to focus on monotropein.Results A total of 370 chemical constituents were identified in M. officinalis using UPLC-Orbitrap-MS/MS technology, including four iridoid glycosides. Through systematic screening, 318 potential therapeutic targets of these iridoid glycosides and 1 001 RA-related targets were identified, with 69 overlapping targets identified. Functional enrichment analysis revealed 478 significant GO terms and 137 KEGG pathways. The results suggest that iridoid glycosides may exert anti-RA therapeutic effects through key targets including TNF, JAK2, STAT3, and PTPRC, potentially modulating critical signaling pathways such as tumor necrosis factor, PI3K-Akt, and JAK-STAT. Molecular docking analysis indicated that monotropein exhibited superior binding affinity compared to other constituents.Conclusion Iridoid glycosides of M. officinalis may exert anti-RA therapeutic effects by targeting TNF, JAK2, STAT3, and PTPRC, and by regulating signaling pathways such as PI3KAkt and JAK-STAT to promote FLS apoptosis.

R285.5

國(guó)家自然科學(xué)基金青年科學(xué)基金項(xiàng)目（82104733）；海南省“南海新星”科技創(chuàng)新人才平臺(tái)項(xiàng)目（NHXXRCXM202317）；孫申田青年人才基金（2021SC-01）；海南省自然科學(xué)基金（825QN330）