目的 利用網(wǎng)絡(luò)藥理學(xué)探討訶子Terminalia chebula治療非小細(xì)胞肺癌的作用機(jī)制，并通過(guò)分子對(duì)接驗(yàn)證。方法 通過(guò)文獻(xiàn)綜述篩選訶子有效活性成分，利用PubChem數(shù)據(jù)庫(kù)、Swiss Target Prediction網(wǎng)站進(jìn)行藥物靶點(diǎn)預(yù)測(cè)。通過(guò)GEO數(shù)據(jù)庫(kù)、GeneCards數(shù)據(jù)庫(kù)、TTD數(shù)據(jù)庫(kù)、DrugBank數(shù)據(jù)庫(kù)檢索、歸納、篩選非小細(xì)胞肺癌相關(guān)靶點(diǎn)。通過(guò)Venn圖對(duì)訶子活性成分作用靶點(diǎn)與非小細(xì)胞肺癌相關(guān)靶點(diǎn)取交集。將共同靶點(diǎn)導(dǎo)入STRING數(shù)據(jù)庫(kù)，構(gòu)建蛋白相互作用（PPI）網(wǎng)絡(luò)。利用DAVID數(shù)據(jù)庫(kù)對(duì)訶子和非小細(xì)胞肺癌潛在的作用靶點(diǎn)進(jìn)行GO功能富集分析及KEGG通路富集分析。通過(guò)AutoDockTools 1.5.6軟件對(duì)訶子成分與非小細(xì)胞肺癌核心靶點(diǎn)進(jìn)行分子對(duì)接驗(yàn)證。結(jié)果 篩選匯總了10種訶子的有效成分，通過(guò)網(wǎng)絡(luò)藥理學(xué)驗(yàn)證玫瑰樹(shù)堿、硫酸奎尼丁、鞣花酸等為藥物主要活性成分。通過(guò)微生信平臺(tái)獲取243個(gè)藥物成分靶點(diǎn)與疾病靶點(diǎn)的交集。受體酪氨酸蛋白激酶erbB-2（ERBB2）、蛋白激酶B1（Akt1）、多肽n-乙酰半乳糖氨基轉(zhuǎn)移酶（GALNT2）等為主要的核心靶點(diǎn)。KEGG通路富集分析顯示主要涉及磷脂酰肌醇3-激酶（PI3K）/Akt信號(hào)通路、癌癥通路等。分子對(duì)接顯示，訶子主要活性成分與預(yù)測(cè)的核心靶點(diǎn)對(duì)接顯示較好的結(jié)合活性。結(jié)論 訶子可能通過(guò)多成分、多靶點(diǎn)作用治療非小細(xì)胞肺癌。

Objective To investigate the mechanism of Terminalia chebula in treating non-small cell lung cancer using network pharmacology, and validate it through molecular docking. Methods Active components of Terminalia chebula were screened via literature review, and their targets were predicted using PubChem and Swiss Target Prediction. Non-small cell lung cancer -related targets were identified from GEO, GeneCards, TTD, and DrugBank databases. Common targets between Terminalia chebula and non-small cell lung cancer were analyzed via Venn diagram. The protein interaction network was algorithmically generated from STRING-derived interaction data. The DAVID database was used to conduct GO functional enrichment analysis and KEGG pathway enrichment analysis on potential targets of Terminalia chebula and non-small cell lung cancer. The molecular docking verification of the Terminalia chebula component with the core target of non-small cell lung cancer was conducted through AutoDockTools 1.5.6 software. Results Ten active components of Terminalia chebula were identified, with ellipticine, quinidine sulfate, ellagic acid as primary candidates. A total of 243 drug component targets and disease targets were identified, including ERBB2, Akt1, and GALNT2. KEGG analysis revealed significant involvement of the PI3K/Akt signaling pathway and cancer-related pathways. Molecular docking showed that the docking results of the main active components of Terminalia chebula with the predicted core targets indicated good binding activity. Conclusion Terminalia chebula may exert therapeutic effects on non-small cell lung cancer through multi-component, multi-target mechanisms.

R285.5

內(nèi)蒙古自治區(qū)自然基金項(xiàng)目（2024MS08067）；2019年度自治區(qū)本級(jí)事業(yè)單位引進(jìn)人才科研啟動(dòng)支持項(xiàng)目（RCQD19003）