目的 基于成分分析、網(wǎng)絡(luò)藥理學(xué)和分子對接技術(shù)探討郁金治療胃癌的作用機制。方法 通過HPLC-Q-TOF-MS/MS技術(shù)及PubChem、SwissTargetPrediction和中藥系統(tǒng)藥理學(xué)數(shù)據(jù)庫與分析平臺（TCMSP）數(shù)據(jù)庫收集郁金的活性成分和相關(guān)靶點；利用Disgenet、GeneCards數(shù)據(jù)庫檢索胃癌疾病靶點，利用韋恩圖繪制平臺獲取共有的關(guān)鍵作用靶點，并將信息導(dǎo)入Cytoscope 3.9.1軟件和STRING在線分析平臺，進(jìn)行網(wǎng)絡(luò)拓?fù)鋵W(xué)分析，構(gòu)建郁金有效成分–核心作用靶點網(wǎng)絡(luò)；基于核心作用靶點通過DAVID數(shù)據(jù)庫進(jìn)行基因本體（GO）和京都基因與基因組百科全書（KEGG）富集分析；然后通過Autodock Tools 1.5.6軟件對有效成分-核心作用靶點進(jìn)行分子對接驗證，得到郁金治療胃癌疾病的關(guān)鍵有效成分。結(jié)果 結(jié)合質(zhì)譜分析與數(shù)據(jù)庫篩選得到郁金化學(xué)成分65個，其中活性成分62個，活性成分的對應(yīng)作用靶點599個，胃癌疾病靶點1 813個，兩者的共同交集靶點262個，對應(yīng)的關(guān)鍵活性成分49個；經(jīng)蛋白質(zhì)相互作用（PPI）及網(wǎng)絡(luò)拓?fù)浞治龊?，獲取核心作用靶點7個，有效成分16個，核心作用靶點分別是表皮生長因子受體（EGFR）、信號轉(zhuǎn)導(dǎo)和轉(zhuǎn)錄激活因子3（STAT3）、絲氨酸/蘇氨酸蛋白激酶1（Akt1）、非受體酪氨酸激酶（SRC）、白細(xì)胞介素-6（IL-6）、熱休克蛋白HSP 90α家族A類成員1（HSP90AA1）、缺氧誘導(dǎo)因子-1α（HIF-1A）；GO富集到基因功能122個，KEGG富集到基因通路71條，分析結(jié)果表明，郁金治療胃癌的作用機制是通過調(diào)節(jié)癌癥通路、缺氧誘導(dǎo)因子1（HIF-1）信號通路、人類巨細(xì)胞病毒感染、腫瘤中程序性死亡配體1（PD-L1）的表達(dá)和程序死亡蛋白1（PD-1）關(guān)卡通路、Th17 細(xì)胞分化、叉頭框蛋白O（FoxO）信號通路、雌激素信號通路、酪氨酸激酶-信號轉(zhuǎn)導(dǎo)和轉(zhuǎn)錄激活因子（JAK/STAT）信號通路、磷脂酰肌醇3激酶（PI3K）-蛋白激酶B（Akt）信號通路等來發(fā)揮治療胃癌的作用。通過分子對接驗證，篩選得到郁金治療胃癌疾病的10個關(guān)鍵有效成分，包括原莪術(shù)二醇、莪術(shù)內(nèi)酯B、雪松烯、β-欖香烯、β-芹子烯、γ-欖香烯、β-cuparenone、新莪術(shù)二酮、石竹烯氧化物、姜黃內(nèi)酯C。結(jié)論 揭示了郁金治療胃癌的有效成分和作用機制，為郁金治療胃癌的臨床實踐及后續(xù)研究提供參考。

Objective Based on component analysis, network pharmacology and molecular docking technology, to explore the effective components and mechanism of Curcumae Radix in treatment of gastric cancer. Methods The active components and related targets of Curcumae Radix were collected by HPLC-Q-TOF-MS/MS technology, PubChem, SwissTargetPrediction, and TCMSP. The targets of gastric cancer diseases were retrieved by using Disgenet and GeneCards databases, and the common key targets were obtained by using Venn mapping platform, and the information was imported into Cytoscope 3.9.1 software and STRING online analysis platform, and the network topology analysis was carried out to construct the effective component-core target network of Curcumae Radix. GO and KEGG were enriched and analyzed by DAVID database based on the core target. Then, the key effective components of Curcumae Radix in treatment of gastric cancer were obtained by molecular docking verification of the effective components-core target through Autodock Tools 1.5.6 software. Results 65 Chemical constituents of Curcumae Radix were obtained by combining mass spectrometry analysis and database screening, including 62 active constituents, 599 corresponding targets of active constituents, 1 813 targets of gastric cancer diseases, 262 common targets and 49 corresponding key active constituents. After protein interaction analysis (PPI) and network topology analysis, 7 core targets and 16 effective components were obtained. The core targets were EGFR, STAT3, Akt1, SRC, IL-6, and HSP90AA1. GO enriched 122 gene functions and KEGG enriched 71 gene pathways. The analysis results showed that, The mechanism of Curcumae Radix in treating gastric cancer is through regulating cancer pathway, HIF-1 signaling pathway, human cytomegalovirus infection, the expression of programmed death ligand 1(PD-L1) and programmed death protein 1 (PD-1) checkpoint pathway, Th17 cell differentiation, foxo signaling pathway, estrogen signaling pathway, tyrosine kinase-signal transduction and transcription. Through molecular docking verification, 10 key effective components of Curcumae Radix for treating gastric cancer were screened out, including protocurcumdiol, curcumolide B, cedrene, β-elemene, β-selinene, γ-elemene, β-cuparenone, new curdione, caryophyllene oxide, and curcumolide C. Conclusion The effective components and mechanism of Curcumae Radix in treatment of gastric cancer were preliminarily revealed, which provided reference for clinical practice and follow-up research of Curcumae Radix in treatment of gastric cancer and the development of anti-gastric cancer drugs.

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國家中醫(yī)藥管理局科技司-浙江省中醫(yī)藥管理局共建科技計劃項目(GZY-ZJ-KJ-24040);杭州市農(nóng)業(yè)與社會發(fā)展科研重點項目(202204A06);浙江中醫(yī)藥大學(xué)中藥飲片有限公司科技創(chuàng)新項目(2022ZZKY001);浙江中醫(yī)藥大學(xué)中藥飲片有限公司科技創(chuàng)新項目(2024ZZKY002)