目的 通過超高效液相色譜-四級桿-飛行時間串聯(lián)質(zhì)譜（UHPLC-Q-TOF/MS）和氣相色譜-質(zhì)譜（GC-MS）鑒定陳皮中的化學(xué)成分，結(jié)合網(wǎng)絡(luò)藥理學(xué)分析其治療“痰、咳、喘”的藥效物質(zhì)基礎(chǔ)及作用機制。方法 建立UHPLC-Q-TOF/MS和GC-MS結(jié)合診斷特征濾過和標(biāo)準(zhǔn)譜庫比較的分析方法，表征陳皮的化學(xué)成分。利用Swiss Target Prediction數(shù)據(jù)庫獲取陳皮主要成分的作用靶點信息；通過GeneCards數(shù)據(jù)庫獲取“痰、咳、喘”相關(guān)的靶點；將陳皮主要成分對應(yīng)靶點與“痰、咳、喘”相關(guān)靶點取交集，借助String平臺和Cytoscape 3.10.0軟件繪制交集靶點蛋白質(zhì)-蛋白質(zhì)相互作用（PPI）網(wǎng)絡(luò)；利用DAVID數(shù)據(jù)庫對核心靶點進(jìn)行基因本體（GO）功能與京都基因與基因組百科全書（KEGG）通路富集分析，通過微生信云平臺對富集結(jié)果可視化。結(jié)果 共鑒定了108個非揮發(fā)性成分和28個揮發(fā)性成分；陳皮的主要活性成分可能為乙酸香茅酯、乙酸香葉酯、（-）-紫蘇醛、（1R，5S）-香芹醇、癸醛、（+）-α-松油醇、（-）-4-萜品醇、芳樟醇、壬醛、桔皮素、甜橙黃酮、異橙黃酮、香葉木素、枸橘苷、日當(dāng)藥黃素；陳皮可能通過熱休克蛋白（HSP90AA1）、表皮生長因子受體（EGFR）、SCR蛋白激酶（SRC）、磷酸化蛋白激酶（AKT1）、磷酸肌醇激酶（PIK3CA）、信號傳導(dǎo)轉(zhuǎn)錄激活因子（STAT1）等關(guān)鍵靶點，協(xié)同調(diào)控磷脂酰肌醇-3-激酶-蛋白激酶B （PI3K-Akt）、Janus激酶-信號傳導(dǎo)和轉(zhuǎn)錄激活蛋白（JAK-STAT）等信號通路發(fā)揮止咳平喘祛痰的治療作用。結(jié)論 分析獲得了陳皮發(fā)揮止咳平喘祛痰功效可能的藥效物質(zhì)基礎(chǔ)及作用機制，可為其質(zhì)量標(biāo)志物和質(zhì)量標(biāo)準(zhǔn)的提升研究奠定基礎(chǔ)。

Objective To identify the chemical constituents in Citri Reticulatae Pericarpium by ultra performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry (UHPLC-Q-TOF/MS) and gas chromatography-mass spectrometry (GC-MS), and to analyze the pharmacological basis of its efficacy in the treatment of phlegm, cough and asthma and its mechanism of action by combining with network pharmacology. Methods A UHPLC-Q-TOF/MS and GC-MS analytical method was established to characterize the chemical constituents of Citri Reticulatae Pericarpium by combining diagnostic feature filtering and comparison of standard spectral libraries. The Swiss Target Prediction database was used to obtain the target information of the main components of Citri Reticulatae Pericarpium; the GeneCards database was used to obtain the targets related to "phlegm, cough and asthma"; The intersection of the main components of Citri Reticulatae Pericarpium and the targets related to "phlegm, cough and asthma" was taken, and the protein-protein interaction (PPI) network of the intersected targets was drawn with the help of the String platform and the Cytoscape 3.10.0 software; the core targets were enriched by the Gene Ontology (GO) function and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway using the DAVID database; the results of the enrichment were visualized by the Microbiology Cloud platform. Results A total of 108 nonvolatile and 28 volatile components were identified; the main active components of Citri Reticulatae Pericarpium may be geranyl acetate, citronellyl acetate, (-)-perillaldehyde, (1R,5S)-carveol, decanal, (+ ) -alpha-terpineol, (-) -terpinen-4-ol, nonanal, linalool, tangeretin, sinensetin, isosinensetin, diosmetin, poncirin and swertiajaponin; Citri Reticulatae Pericarpium may exert the therapeutic effects of cough suppressant, asthma and expectorant through the synergistic regulation of PI3K-Akt, JAK-STAT signaling pathways via the key targets of HSP90AA1, EGFR, SRC, AKT1, PIK3CA, STAT1 and so on. Conclusion The possible pharmacological basis and mechanism of action of Citri Reticulatae Pericarpium in relieving cough, asthma and phlegm were analyzed, which can lay the foundation for the improvement of its quality markers and quality standards.

R284,R285.5

廣西青年科學(xué)基金資助項目（2023GXNSFBA026276）;廣西科技基地與人才專項（桂科AD21238032）;國家重大新藥創(chuàng)制科技重大專項資助項目（2019ZX09201004）;國家自然科學(xué)基金資助項目（82160771）;廣西中醫(yī)藥大學(xué)博士科研啟動項目（2020BS015）;廣西中醫(yī)藥大學(xué)青年科學(xué)基金資助項目（2021QN006）;廣西中醫(yī)藥大學(xué)第三批“岐黃工程”高層次人才團(tuán)隊培育項目（202406）