[關(guān)鍵詞]
[摘要]
目的 利用網(wǎng)絡(luò)藥理學(xué)探討訶子Terminalia chebula治療非小細胞肺癌的作用機制,并通過分子對接驗證。方法 通過文獻綜述篩選訶子有效活性成分,利用PubChem數(shù)據(jù)庫、Swiss Target Prediction網(wǎng)站進行藥物靶點預(yù)測。通過GEO數(shù)據(jù)庫、GeneCards數(shù)據(jù)庫、TTD數(shù)據(jù)庫、DrugBank數(shù)據(jù)庫檢索、歸納、篩選非小細胞肺癌相關(guān)靶點。通過Venn圖對訶子活性成分作用靶點與非小細胞肺癌相關(guān)靶點取交集。將共同靶點導(dǎo)入STRING數(shù)據(jù)庫,構(gòu)建蛋白相互作用(PPI)網(wǎng)絡(luò)。利用DAVID數(shù)據(jù)庫對訶子和非小細胞肺癌潛在的作用靶點進行GO功能富集分析及KEGG通路富集分析。通過AutoDockTools 1.5.6軟件對訶子成分與非小細胞肺癌核心靶點進行分子對接驗證。結(jié)果 篩選匯總了10種訶子的有效成分,通過網(wǎng)絡(luò)藥理學(xué)驗證玫瑰樹堿、硫酸奎尼丁、鞣花酸等為藥物主要活性成分。通過微生信平臺獲取243個藥物成分靶點與疾病靶點的交集。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。KEGG通路富集分析顯示主要涉及磷脂酰肌醇3-激酶(PI3K)/Akt信號通路、癌癥通路等。分子對接顯示,訶子主要活性成分與預(yù)測的核心靶點對接顯示較好的結(jié)合活性。結(jié)論 訶子可能通過多成分、多靶點作用治療非小細胞肺癌。
[Key word]
[Abstract]
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.
[中圖分類號]
R285.5
[基金項目]
內(nèi)蒙古自治區(qū)自然基金項目(2024MS08067);2019年度自治區(qū)本級事業(yè)單位引進人才科研啟動支持項目(RCQD19003)