目的 運用網(wǎng)絡藥理學方法和分子對接技術探討黃芩抗糖尿病心肌病的活性成分及潛在的作用機制,為后續(xù)開展實驗研究提供生物信息學基礎。方法 通過TCMSP數(shù)據(jù)庫及Swiss Target Prediction數(shù)據(jù)搜集黃芩活性成分與靶點;采用GeneCards、OMIM數(shù)據(jù)庫查找糖尿病心肌病相關靶點;利用Venny 2.1.0獲取藥物和糖尿病心肌病的交集靶點;借助String平臺和Cytoscape 3.9.0軟件拓撲分析并篩選出核心成分及靶點;利用DAVID數(shù)據(jù)庫進行黃芩治療糖尿病心肌病靶點基因本體(GO)分析和基因組百科全書(KEGG)通路富集分析;采用AutoDock 1.5.7和PyMOL 2.4.1軟件進行分子對接及可視化作圖。結果 共篩選出36個黃芩活性成分,與糖尿病心肌病的151個交集靶點。GO富集分析得到775條生物過程,167條分子功能,86條細胞組分;KEGG通路分析得到169條,其中晚期糖基化終末產(chǎn)物及其受體(AGE-RAGE)、磷脂酰肌醇-3-激酶(PI3K)-蛋白激酶B(Akt)、絲裂原活化蛋白激酶(MAPK)、腫瘤壞死因子(TNF)、低氧誘導因子-1(HIF-1)是較關鍵的通路。分子對接結果顯示,漢黃芩素、黃芩素、表小檗堿、黃芩新素等與Akt1、TNF、甘油醛-3-磷酸脫氫酶(GAPDH)、白細胞介素-6(IL-6)蛋白等有較強的相互作用,其中與黃芩素結合性最好。結論 黃芩對糖尿病心肌病的治療作用可能是漢黃芩素、黃芩素、表小檗堿、黃芩新素等活性成分通過調控Akt1、TNF、GAPDH、IL-6等靶點,作用于AGE-RAGE、PI3K-Akt、MAPK等信號通路來實現(xiàn)的。

Objective To explore the active ingredients and potential mechanism of Scutellariae Radix anti-diabetic cardiomyopathy by network pharmacology and molecular docking techniques, and to provide a bioinformatics basis for further experimental studies. Methods The effective components and drug targets of Scutellariae Radix were collected by TCMSP database and SwissTargetPrediction data. GeneCards and OMIM databases were used to identify diabetic cardiomyopathy-related targets. Using Venny 2.1.0 obtain crossover targets of drug and diabetic cardiomyopathy. With String Platform and Cytoscape 3.9.0 Software topology analysis and screening of nucleotide components and targets. DAVID databases was used to analyze the KEGG and GO enrichment pathway of Scutellariae Radix against diabetic cardiomyopathy. Finally, AutoDock1.5.6 and PyMOL2.4.1 software were used for molecular docking and visualization. Results A total of 36 active ingredients of Scutellariae Radix were screened, and 151 crossover targets were identified. GO enrichment analysis yielded 775 biological processes, 167 molecular functions and 86 cellular components. KEGG pathway analysis was performed on 169 genes, of which AGE-RAGE, PI3K-Akt, MAPK, TNF, and HIF-1 were the more critical pathways. Molecular docking results showed that wogonin, baicalein, epiberberine, Skullcapflavone II had strong interaction with Akt1, TNF, GAPDH, IL-6 proteins, among which the binding with baicalein was the best. Conclusion Effect of Scutellariae Radix on diabetic cardiomyopathy may be realized by the regulation of Akt1, TNF, GAPDH1, IL-6 and other core targets by active ingredients such as wogonin, baicalein, epiberberine, and Skullcapflavone II, acting on AGE-RAGE, PI3K-Akt, MAPK, and other signaling pathways to achieve.

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貴州省衛(wèi)生健康委員會科學技術基金項目(gzwkj2021-461)；貴州省高層次創(chuàng)新型人才“千層次”人才培養(yǎng)項目(GZSYQCC[2023]008)