目的 通過 HPLC-Q-TOF-MS/MS分析小兒佛芍和中顆粒（XFHG）中的化學(xué)成分，依據(jù)解析的化學(xué)成分結(jié)合網(wǎng)絡(luò)藥理學(xué)預(yù)測其治療功能性腹痛的藥效物質(zhì)基礎(chǔ)，篩選出潛在功效成分，預(yù)測作用機(jī)制。方法 采用HPLC-Q-TOF-MS/MS對XFHG進(jìn)行化學(xué)成分分析，分別在正、負(fù)離子模式下掃描，結(jié)合對照品與中藥系統(tǒng)藥理學(xué)數(shù)據(jù)庫與分析平臺（TCMSP）、文獻(xiàn)中的碎片離子信息、保留時間進(jìn)行匹配，確認(rèn)化學(xué)成分。篩選質(zhì)譜解析得到的化學(xué)成分中口服生物利用度≥20%、類藥性≥0.5 的成分，同時納入《中國藥典》2020 年版中規(guī)定的指標(biāo)成分以及 SwissADME 數(shù)據(jù)庫篩選得到的成分作為活性成分；通過TCMSP、Massbank、本草組鑒數(shù)據(jù)庫、Genecards數(shù)據(jù)庫及文獻(xiàn)篩選，分別建立XFHG活性成分靶點(diǎn)數(shù)據(jù)庫、功能性腹痛相關(guān)疾病的靶點(diǎn)數(shù)據(jù)庫，篩選出共同靶點(diǎn)，導(dǎo)入網(wǎng)絡(luò)可視化軟件 Cytoscape 3.9.1中，構(gòu)建“XFHG-成分-功能性腹痛”靶點(diǎn)相互作用網(wǎng)絡(luò)圖，篩選出核心成分；共有靶點(diǎn)導(dǎo)入STRING11.5數(shù)據(jù)庫中，構(gòu)建蛋白質(zhì)-蛋白質(zhì)相互作用（PPI）網(wǎng)絡(luò)圖，并將得到的數(shù)據(jù)導(dǎo)入Cytoscape 3.9.1中，篩選出核心作用的靶點(diǎn)；將核心靶點(diǎn)導(dǎo)入DAVID數(shù)據(jù)庫進(jìn)行京都基因與基因組百科全書（KEGG）通路和基因本體（GO）富集分析。結(jié)果 XFHG定性分析中共解析出96個化學(xué)成分，包括26個黃酮類、17個有機(jī)酸類、13個萜類、11個生物堿類、6個檸檬苦素類、8個苯丙素類、4個苯乙醇苷類及11個其他類；篩選出發(fā)揮治療功能性腹痛作用的核心成分 15 個，來源于 6 味藥材，包括小檗堿、芍藥苷、連翹酯苷 A、連翹苷、吳茱萸堿、吳茱萸次堿等；XFHG 治療功能性腹痛的核心靶點(diǎn)有 TNF、AKT1、IL6、IL-1β、VEGFA、TP53、CASP3、PTGS2、CAT、MAPK3；KEGG 通路分析共得到 109 條通路，免疫應(yīng)答、炎癥反應(yīng)相關(guān)的信號通路排名靠前；GO 富集分析得到生物過程（BP）條目 145 個、細(xì)胞組分（CC）條目10個、分子功能（MF）條目9個，富集值排名靠前的條目涉及脂多糖介導(dǎo)的信號通路、糖皮質(zhì)激素反應(yīng)、一氧化氮生物合成過程的正向調(diào)控等與炎癥反應(yīng)相關(guān)的生物過程。結(jié)論 根據(jù)HPLC-Q-TOF-MS/MS解析的化學(xué)成分結(jié)合網(wǎng)絡(luò)藥理學(xué)預(yù)測了XFHG治療功能性腹痛的潛在功效成分，預(yù)測其作用機(jī)制與免疫調(diào)節(jié)、抗炎相關(guān)。

Objective To Analyze the chemical composition of Xiaoer Foshao Hezhong Granules (XFHG) by HPLC-Q-TOF-MS/ MS, then predicting the pharmacodynamic substance basis of treating functional abdominal pain based on its chemical composition and network pharmacology, checking out the potential efficacy ingredients and mechanism of action.Methods HPLC-Q-TOF-MS/ MS was used to analyze the chemical composition of XFHG, which were scanned in positive and negative modes respectively. The chemical composition was confirmed by matching the reference substance with the fragment ion information and retention time in the Systems Pharmacology Database and Analysis Platform of traditional Chinese medicine (TCMSP) and literatures. The chemical components obtained through mass spectrometry analysis with oral bioavailability ≥ 20% and drug like properties ≥ 0.5 were selected, and the target components specified in the 2020 edition of the Chinese Pharmacopoeia and the components screened from the SwissADME database were included as active ingredients. By using TCMSP, Massbank, Herbal Pharmacopoeia Database, Genecards Database, and literature screening, we established target databases for active ingredients of XFHG, as well as target databases for functional abdominal pain related diseases. We screened common targets and imported them into the network visualization software Cytoscape 3.9.1 to construct a target interaction network diagram for "XFHG-components-functional abdominal pain", and screened the core components. Import common targets into the STRING 11.5 database, construct a protein protein interaction (PPI) network diagram, and import the obtained data into Cytoscape 3.9.1 to screen out the core targets. The core targets were imported into the DAVID database for Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) enrichment analysis.Results There were 96 chemical components analyzed by qualitative analysis of XFHG, including 26 flavonoids, 17 organic acids, 13 terpenoids, 11 alkaloids, 6 lemon, 8 phenylpropanoids, 4 benzylethanol side and 11 other classes. Screening out 15 core components that play a therapeutic role in functional abdominal pain, sourced from six medicinal herbs, including berberine, paeoniflorin, forsythrin A, forsythrin, evodiamine, rutaecarpine, etc. The core targets of XFHG for treating functional abdominal pain include TNF, AKT1, IL6, IL-1β, VEGFA, TP53, CASP3, PTGS2, CAT, and MAPK3. A total of 109 pathways were identified through KEGG pathway analysis, with immune response and inflammatory response related signaling pathways ranking high. GO enrichment analysis yielded 145 entries for biological processes (BP), 10 entries for cellular components (CC), and nine entries for molecular functions (MF). The entries with the highest enrichment values involved biological processes related to inflammation, such as lipopolysaccharide-mediated signaling pathways, glucocorticoid responses, and positive regulation of nitric oxide biosynthesis processes.Conclusion Based on the chemical components analyzed by HPLC-Q-TOF-MS/ MS combined with network pharmacology, the potential efficacy components of XFHG in the treatment of functional abdominal pain were predicted, and its mechanism of action was predicted to be related to immune regulation and anti-inflammatory effects.

R284.1，R285.5

2021年國家中醫(yī)藥管理局岐黃學(xué)者項目