目的 基于網(wǎng)絡藥理學與分子對接技術(shù)探討廣藿香抗肝癌的作用靶點及信號通路，闡明其可能的作用機制。方法 通過中藥系統(tǒng)藥理學數(shù)據(jù)庫與分析平臺（TCMSP）數(shù)據(jù)庫檢索廣藿香的化學成分、作用靶點，運用Uniprot數(shù)據(jù)庫對靶點名稱進行規(guī)范，利用GeneCards數(shù)據(jù)庫及OMIM數(shù)據(jù)庫收集肝癌作用靶點，使用Venny 2.1網(wǎng)站將廣藿香作用靶點與肝癌靶點取交集，通過STRING平臺構(gòu)建蛋白質(zhì)相互作用（PPI）網(wǎng)絡圖，采用DAVID網(wǎng)站進行基因本體（GO）功能富集分析和京都基因與基因組百科全書（KEGG）通路富集分析。通過Cytoscape 3.8.2軟件用于構(gòu)建“藥物-活性成分-靶點-疾病”網(wǎng)絡，篩選出核心靶點，并將活性成分與排名前5位的核心靶點進行分子對接。結(jié)果 篩選出10個廣藿香主要活性成分及165個活性成分作用靶點，123個交集靶點。核心靶點為蛋白激酶B（Akt）、腫瘤蛋白P53（TP53）、白細胞介素-6（IL-6）、轉(zhuǎn)錄因子AP-1（JUN）、半胱氨酸天冬氨酸蛋白酶（CASP3）。GO分析表明廣藿香對肝癌的治療作用主要涉及RNA聚合酶Ⅱ啟動子轉(zhuǎn)錄的正調(diào)控、轉(zhuǎn)錄的正調(diào)控和DNA模板化等283條生物過程，蛋白質(zhì)結(jié)合、相同蛋白質(zhì)結(jié)合和RNA聚合酶Ⅱ核心啟動子近端區(qū)序列特異性DNA結(jié)合等57個分子功能，核和胞質(zhì)溶膠等26個細胞組分；KEGG富集分析得到95條信號通路，主要包括癌癥通路、乙型肝炎、人類T淋巴細胞病毒Ⅰ（HTLV-I）感染、腫瘤蛋白、磷脂酰肌醇3-激酶（PI3K）/Akt等信號通路。分子對接結(jié)果顯示，廣藿香有效成分能夠與核心靶點有效結(jié)合。結(jié)論 廣藿香可通過作用于Akt1、TP53、IL-6、JUN、CASP3等靶點，調(diào)控乙型肝炎、HTLV-I感染、PI3K/Akt等信號通路發(fā)揮肝癌治療作用。

Objective To analysis the targets, signal pathways and possible mechanisms of action of Pogostemonis Herba in treatment of liver cancer based on the method of network pharmacology and molecular docking. Methods The TCMSP database was used to screen the chemical components and targets of Pogostemonis Herba, the Uniprot database was used to query the corresponding genes of the target, the Genecards database and the online human Mendelian Inheritance (OMIM) database were used to collect the targets of liver cancer. Venny 2.1 was used to intersect the target of Pogostemonis Herba and the target of liver cancer, and build a protein interaction (PPI) network through the STRING platform. DAVID was used for GO enrichment analysis and KEGG analysis. Visual analysis was performed by Cytoscape 3.8.2 software. Cytoscape 3.8.2 software was used to construct the “drug-active ingredient-target-disease” network, screen out the core targets, and docked the active ingredients with the top five core targets. Results 10 Compounds and 165 corresponding targets were screened from Pogostemonis Herba medicinal materials. 123 Key targets were obtained by intersecting the regulatory targets of the main active components of Pogostemonis Herba and the targets of liver cancer. Akt, TP53, IL-6, JUN, and CASP3 were key targets. The GO analysis showed that the therapeutic effect of Pogostemonis Herba on liver cancer mainly involves 283 biological processes such as positive regulation of transcription from RNA polymerase Ⅱ promoter and positive regulation of transcription, DNA-templated, 57 molecular functions such as protein binding, identical protein binding, and RNA polymerase Ⅱ core promoter proximal region sequence-specific DNA binding, as well as 26 cellular components such as nucleus and cytosol; Through KEGG enrichment analysis, 95 signaling pathways were identified, mainly including pathways in cancer, hepatitis B, HTLV-I infection, tumor proteins, PI3K/Akt, and other signaling pathways. The effective components of Pogostemonis Herba can effectively combine with core targets. Conclusion Pogostemonis Herba can play an anti-hepatoma role by acting on targets such as Akt1, TP53, IL-6 and regulating hepatitis B, HTLV-I infection, PI3K/Akt and other signal pathways.

R285.5

湖北省中醫(yī)藥管理局2023—2024年度中醫(yī)藥科研項目（ZY2023M037）；深圳市“醫(yī)療衛(wèi)生三名工程”項目（SZZYSM202106004）；深圳市寶安區(qū)醫(yī)療衛(wèi)生基礎(chǔ)研究項目（2021JD166）；國藥東風總醫(yī)院青年人才項目（2023Q01，2023Q02）