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| 基于网络药理学和分子对接探讨黄连温胆汤“异病同治”胆囊胆固醇结石和冠心病的作用机制 |
| 梁磊,彭鑫,王天麟,冯彬彬,张雨田,韩俊泉,曲鹏飞,贺燕丽,王红 |
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| 天津中医药大学天津 301617;天津中医药大学第二附属医院天津 300250 |
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| 摘要: |
| 目的:借助网络药理学与分子对接技术探讨黄连温胆汤“异病同治”胆囊胆固醇结石(CG)和冠心病(CHD)的作用机制。方法:利用传统中药系统药理学数据库与分析平台(TCMSP)、中医药整合药理学研究平台数据库(TCMIP)获取黄连温胆汤的潜在活性成分及其作用靶点，使用GeneCards、OMIM数据库筛选两种疾病靶点，借助Venny 2.1将上述筛选的药物活性成分作用靶点与疾病相关靶点取交集，使用Cytoscape 3.10.2软件构建“中药-活性成分-靶点-疾病”网络。通过STRING数据库对交集靶点进行蛋白质互作分析，使用DAVID数据库对共有靶点进行基因本体(GO)功能分析和京都基因与基因组百科全书(KEGG)通路富集分析，利用Autodock Vina对关键靶点进行分子对接并验证结合活性。结果:共筛选出135个黄连温胆汤有效成分及947个潜在作用靶点，与两种疾病的交集靶点207个；PPI网络拓扑分析筛选出肿瘤坏死因子(TNF)、白细胞介素-6(IL-6)、丝氨酸/苏氨酸蛋白激酶(AKT1)、白蛋白(ALB)、肿瘤蛋白53(TP53)等核心靶点；GO功能富集分析涉及生物过程854项，细胞组成92项，分子功能206项，KEGG主要富集在脂质与动脉粥样硬化、流体剪切应力与动脉粥样硬化、磷脂酰肌醇3激酶/蛋白激酶B(PI3K/AKT)、TNF信号通路、IL-17信号通路和腺苷酸活化蛋白激酶(AMPK)等相关通路；分子对接结果表明，黄连温胆汤主要活性成分与疾病核心靶点具有较好的构象。结论:黄连温胆汤可能作用于TNF、IL-6、AKT1、ALB、TP53等关键靶点，调控PI3K/AKT、AMPK、TNF和IL-17信号通路发挥“胆心同治”的作用。 |
| 关键词: 黄连温胆汤 胆固醇结石 冠心病 网络药理学 分子对接 |
| DOI：10.3969/j.issn.1007-6948.2025.05.023 |
| 投稿时间：2025-03-04 |
| 基金项目:国家自然科学基金(82274522)；天津市名中医工作室项目(津卫中〔2024〕61号) |
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| Mechanism of Huanglian Wendan decoction in treatment of cholesterol gallstones and coronary heart disease based on network pharmacology and molecular docking |
| LIANG Lei,PENG Xin,WANG Tian-lin |
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| Abstract: |
| Objective To explore the mechanism of Huanglian Wendan decoction in treatment of cholesterol gallstones and coronary heart disease based on network pharmacology and molecular docking. Methods The potential active components and their action targets of Huanglian Wendan decoction were obtained from the TCMSP and TCMIP databases. The disease targets of two disease were screened from the GeneCards and OMIM databases. The intersection of the drug active component action targets and disease-related targets was obtained by using Venny 2.1. The “Chinese medicine-active component-target-disease” network was constructed by using Cytoscape 3.10.2 software. The protein-protein interaction analysis of the intersection targets was conducted through the STRING database. The gene ontology (GO) functional analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the common targets were performed by using the DAVID database. The molecular docking of the core component key targets was verified by using Autodock Vina to confirm the binding activity. Results A total of 135 active components and 947 potential targets of Huanglian Wendan decoction were identified, with 207 overlapping targets associated with the two diseases. The PPI network topology analysis revealed key targets including TNF, IL-6, Akt1, ALB and TP53. GO enrichment analysis covered 854 biological processes, 92 cellular components and 206 molecular functions. KEGG pathway analysis highlighted significant enrichment in pathways related to lipid metabolism and atherosclerosis, fluid shear stress and atherosclerosis, PI3K/Akt signaling, TNF signaling, IL-17 signaling and AMPK signaling. Molecular docking studies demonstrated that the primary active components of Huanglian Wendan decoction exhibited favorable binding conformations with these core disease targets. Conclusion Huanglian Wendan decoction may act on key targets such as TNF, IL-6, Akt1, ALB, TP53 and regulate PI3K/Akt, AMPK, TNF and IL-17 signaling pathways to play a role of “Treating gallbladder and heart together”. |
| Key words: Huanglian Wendan decoction cholesterol gallstones coronary heart disease network pharmacology molecular docking |
