目的 基于超高效液相色譜-線性離子阱串聯(lián)靜電場軌道高分辨質(zhì)譜（UHPLC-LTQ-Orbitrap-MS/MS）技術(shù)、網(wǎng)絡(luò)藥理學(xué)和分子對接探究蒲公英改善高脂血癥的有效成分及其作用機(jī)制。方法 根據(jù)質(zhì)譜信息結(jié)合對照品裂解規(guī)律并參考文獻(xiàn)指認(rèn)蒲公英中化學(xué)成分；利用STITCH、SwissTargetPredection、TCMSP數(shù)據(jù)庫構(gòu)建蒲公英的潛在藥效成分靶點(diǎn)數(shù)據(jù)庫，通過GeneCards、DrugBank、OMIM、TherapeuticTargetDatabase、PharmGKB獲取血脂異常潛在靶點(diǎn)；使用STRING數(shù)據(jù)庫構(gòu)建關(guān)鍵靶點(diǎn)蛋白相互作用（PPI）網(wǎng)絡(luò)；通過Metascape數(shù)據(jù)庫對關(guān)鍵靶點(diǎn)進(jìn)行基因本體論（GO）功能與京都基因與基因組百科全書（KEGG）信號通路富集分析；借助Cytoscape軟件構(gòu)建"活性成分-靶點(diǎn)-通路"網(wǎng)絡(luò)；采用分子對接技術(shù)進(jìn)行虛擬驗(yàn)證。結(jié)果 從蒲公英中共鑒別出126個(gè)化合物，包括黃酮類58個(gè)，有機(jī)酸類29個(gè)，萜類23個(gè)，苯丙素8個(gè)，核苷類3個(gè)和其他類5個(gè)。網(wǎng)絡(luò)藥理學(xué)研究表明，蒲公英可能通過槲皮素、異鼠李素、香葉木素、白楊素、芹菜素等成分作用于碳酸酐酶2（CA2）、碳酸酐酶7（CA7）、醛糖還原酶（AKR1B1）、基質(zhì)金屬蛋白酶2（MMP-2）、蛋白激酶1（Akt1）等核心靶點(diǎn)，來調(diào)節(jié)脂質(zhì)和動(dòng)脈粥樣硬化、磷脂酰肌醇-3-激酶（PI3K）/Akt、絲裂原活化蛋白激酶（MAPK）、流體剪切應(yīng)力和動(dòng)脈粥樣硬化和晚期糖基化終末產(chǎn)物（AGE）/AGEs受體（RAGE）等信號通路，從而發(fā)揮調(diào)血脂作用；分子對接驗(yàn)證結(jié)果表明，蒲公英改善高脂血癥有效成分與疾病靶點(diǎn)蛋白具有較強(qiáng)的結(jié)合活性。結(jié)論 蒲公英可能通過調(diào)控脂質(zhì)代謝、炎癥反應(yīng)、內(nèi)質(zhì)網(wǎng)應(yīng)激、氧化應(yīng)激和免疫調(diào)節(jié)等多方面發(fā)揮改善高脂血癥的作用。

Objective To investigate the active components and its mechanism for improving hyperlipidemia of Taraxacum mongolicum Hand.-Mazz. using UHPLC-LTQ-Orbitrap-MS/MS, network pharmacology and molecular docking. Methods Chemical composition of Taraxacum mongolicum was identified by mass spectrometry information combined with the fragmentation patterns of reference compounds and references. Potential pharmacological targets of Taraxacum mongolicum were screened using STITCH, SwissTargetPrediction, and TCMSP databases, while potential targets for dyslipidemia were obtained from GeneCards, DrugBank, OMIM, TherapeuticTarget, and PharmGKB Database. PPI network of key targets was constructed using STRING database. Key targets were subjected to GO and KEGG pathway enrichment analysis using Metascape database. The active ingredient-target-pathway network was built using Cytoscape software. Finally, molecular docking verification was performed between the active ingredients and the key targets. Results A total of 126 compounds were identified from Taraxacum mongolicum, including 58 flavonoids, 29 organic acids, 23 terpenes, 8 coumarins, 3 nucleosides, and 5 other compounds. Network pharmacology studies showed that Taraxacum mongolicum may act on CA2, CA7, AKR1B1, MMP-2, AKT1, and other core targets through quercetin, isorhamnetin, diosmetin, chrysin, apigenin, and other components. It regulates lipid and atherosclerosis, PI3K/Akt, MAPK, fluid shear stress and atherosclerosis, and AGE/RAGE signaling pathways to play a role in regulating blood lipids. Molecular docking validation results demonstrate that the active components exhibit strong binding activity with disease target proteins. Conclusion Taraxacum mongolicum may play a role in improving hyperlipidemia by regulating lipid metabolism, inflammatory response, endoplasmic reticulum stress, oxidative stress and immunomodulation.

R285

國家自然科學(xué)基金青年基金資助項(xiàng)目（81503244）；北京中醫(yī)藥大學(xué)縱向發(fā)展基金項(xiàng)目（2019-ZXFZJJ-052）