摘要
目的:基于网络药理学和分子对接技术探讨瓜蒌薤白半夏汤“异病同治”冠状动脉微血管疾病(CMVD)和高脂血症(HLP)的物质基础和作用机制。方法:通过中药系统药理学数据库和分析平台(TCMSP)挖掘瓜蒌薤白半夏汤的活性成分及靶点。借助GeneCards和OMIM数据库查询CMVD和HLP的相关靶点。构建Venn图得到瓜蒌薤白半夏汤与CMVD和HLP的共同靶点。通过Cytoscape 3.10.0软件绘制“瓜蒌薤白半夏汤-活性成分-共同靶点”网络图,并筛选核心活性成分。运用STRING数据库构建蛋白-蛋白互作(PPI)网络,筛选核心靶点。利用DAVID数据库对共有基因进行基因本体(GO)功能富集分析、京都基因与基因组百科全书(KEGG)通路富集分析。运用AutoDock Vina 1.5.7软件将核心活性成分与核心靶点进行分子对接。结果:共得到瓜蒌薤白半夏汤主要活性成分35种,筛选出豆甾醇、槲皮素、黄芩苷、柚皮素等30种核心活性成分。83个共同靶点中筛选得到32个核心靶点,主要涉及丝氨酸/苏氨酸蛋白激酶(AKT1)、白细胞介素6(IL6)、白细胞介素-1β(IL1B)、缺氧诱导因子-1α(HIF1A)、胱天蛋白酶3(CASP3)等。GO分析中,生物过程主要包括对长波紫外线(UV-A)的反应、化学信号对心脏收缩力的调节、平滑肌增生、氮利用调控和脂肪酸代谢过程的正向调节等;细胞组分主要包括丝氨酸型肽酶复合物、酪氨酸激酶受体复合物、丝氨酸蛋白酶抑制剂复合物、转录因子激活蛋白-1(AP-1)复合体和Bcl-2家族蛋白复合物等;分子功能主要包括一氧化氮合酶活性、四氢生物蝶呤、雌激素反应元件结合、表皮生长因子受体3(ErbB-3)类受体结合和一氧化氮合酶调节剂活性等。KEGG富集通路主要涉及癌症信号通路、晚期糖化终产物-晚期糖化终产物受体(AGE-RAGE)信号通路在糖尿病并发症中的作用、血流剪切力调控动脉粥样硬化信号通路、肿瘤坏死因子信号通路、脂质与动脉粥样硬化信号通路和缺氧诱导因子-1(HIF-1)信号通路等。分子对接结果显示,核心活性成分与核心靶点蛋白的结合活性均较好,活性成分与靶蛋白具有强烈的结合活性。结论:瓜蒌薤白半夏汤可能通过多靶点、多通路发挥对CMVD和HLP的治疗作用。
Objective:To explore the material basis and mechanism of Gualou Xiebai Banxia Decoction for treating coronary microvascular disease(CMVD)and hyperlipidemia(HLP)by"treating different diseases with same method"based on network pharmacology and molecular docking technology.Methods:The active ingredients and targets of Gualou Xiebai Banxia Decoction were obtained using the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform(TCMSP).Query the relevant targets of CMVD,and HLP were screened by GeneCards and OMIM databases.The Venn map was constructed to obtain the common targets of Gualou Xiebai Banxia Decoction with CMVD and HLP.The network diagram of"Gualou Xiebai Banxia Decoction-active ingredients-common targets"was drawn by Cytoscape 3.10.0 software,and the core active ingredients were screened.The STRING database was used to construct the protein-protein interaction(PPI)network and to screen the core targets.The DAVID database was used to conduct gene ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis on common genes.The core active ingredients were analyzed for molecular docking with the core targets using the AutoDock Vina 1.5.7 software.Results:A total of 35 main active ingredients of Gualou Xiebai Banxia Decoction were obtained,and 30 core active ingredients such as stigmasterol,quercetin,baicalein and naringenin were screened out.Among the 83 common targets,32 core targets were screened out,mainly involving serine/threonine protein kinase(AKT1),interleukin-6(IL6),interleukin-1β(IL1B),hypoxia-inducible factor-1α(HIF1A),Caspase 3(CASP3).In GO analysis,the biological processes mainly included the response to long-wave ultraviolet(UV-A),the regulation of cardiac contractility by chemical signals,smooth muscle proliferation,the regulation of nitrogen utilization,and the positive regulation of fatty acid metabolism processes.The cellular components mainly included serine peptidase complexes,tyrosine kinase receptor complexes,serine protease inhibitor complexes,transcription factor activating protein-1(AP-1)complexes and Bcl-2 family protein complexes.The molecular functions mainly included nitric oxide synthase activity,tetrahydrobiopterin,estrogen response element binding,epidermal growth factor receptor 3(ErbB-3)receptor binding,and nitric oxide synthase modulator activity.The KEGG enrichment pathway mainly included to the cancer signaling pathway,the role of the advanced glycation end product-advanced glycation end product receptor(AGE-RAGE)signaling pathway in diabetic complications,the regulation of blood flow shear force in the atherosclerotic signaling pathway,the tumor necrosis factor signaling pathway,the lipid and atherosclerotic signaling pathway,and the hypoxia-inducible factor-1(HIF-1)signaling pathway.The results of molecular docking showed that the binding activities of the core active ingredients and the core target proteins were better,and the active ingredients showed some strong binding activity with the target proteins.Conclusion:Gualou Xiebai Banxia Decoction might play therapeutic effects on CMVD and HLP through multiple targets and multiple pathways.
作者
鞠彤彤
胡继强
JU Tongtong;HU Jiqiang(Beijing University of Chinese Medicine,Beijing 100029,China;Dongfang Hospital,Beijing University of Chinese Medicine,Beijing 100071,China)
出处
《中西医结合心脑血管病杂志》
2025年第14期2081-2091,共11页
Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease
基金
首都卫生发展科研专项(No.首发2020-2-4203)
国家中医药管理局第二批全国西医学习中医优秀人才研修项目,编号:国中医药人教函〔2023〕90号
中医药临床循证研究专项。
关键词
冠状动脉微血管疾病
高脂血症
瓜蒌薤白半夏汤
网络药理学
异病同治
分子对接
作用机制
coronary microvascular disease
hyperlipidemia
Gualou Xiebai Banxia Decoction
network pharmacology
treating different diseases with same method
molecular docking
mechanism
