[关键词]
[摘要]
目的 以经典名方桃红四物汤养血、活血、逐瘀功效为核心,通过构建"成分-靶点-通路-疾病"作用网络探讨其临床异病同治的作用机制。方法 利用生物科学与网络药理学平台、蛋白数据库和String数据库收集桃红四物汤化学成分及其相关靶点数据,建立"成分-靶点"作用网络;基于筛选得到的靶点,对桃红四物汤治疗的疾病进行关联分析,建立"靶点-疾病"网络;进而开展基因本体论(gene ontology,GO)和基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)通路富集分析桃红四物汤治疗疾病的关键通路;同时将筛选得到的关键有效成分和核心靶点进行分子对接验证,综合探讨桃红四物汤在临床上异病同治的复杂作用网络。结果 从桃红四物汤中筛选出40个活性化合物,其中32个成分涉及221个相关靶点、286种相关疾病。其中阿魏酸、山柰酚、槲皮素、丹皮酚、芍药苷、藁本内酯、咖啡酸能匹配到较多靶点。预测到桃红四物汤可治疗疾病主要包括3大类,分别为癌症相关疾病(乳腺癌、前列腺癌等)、心血管疾病(高血压、心肌梗死、心脏衰竭)、神经系统疾病;核心靶点蛋白涉及RAC-α丝氨酸/苏氨酸蛋白激酶、血清白蛋白、白细胞介素17、血管内皮生长因子A、转录因子AP-1等;KEGG信号涉及促进肿瘤细胞凋亡和抑制肿瘤增生、免疫调节、血液循环系统调节、内分泌调节等多种生物过程的165条通路。结论 构建了桃红四物汤"成分-靶点-通路-疾病"之间的关联,一定程度上揭示桃红四物汤多成分、多靶点的复杂作用机制,为经典名方桃红四物汤的临床广泛应用提供理论基础。
[Key word]
[Abstract]
Objective Based on the efficacy of the classic prescription Taohong Siwu Decoction (桃红四物汤) for nourishing blood, promoting blood circulation, and removing blood stasis, the mechanism of Taohong Siwu Decoction in treating different clinical diseases with the same treatment was explored by constructing a "component-target-pathway-disease" action network. Methods Using biological science and network pharmacology platform, protein database and string database to collect the chemical components and related target data of Taohong Siwu Decoction and establish the "component-target" action network. Based on the selected targets, the association analysis of diseases treated by Taohong Siwu Decoction was carried out, and the "target-disease" network was established; The GO and KEGG pathway enrichment analysis of Taohong Siwu Decoction were carried out. The key effective components and targets screened were verified by molecular docking, and the complex network of Taohong Siwu Decoction in treating different diseases in clinic was comprehensively discussed. Results A total of 40 active compounds were screened from Taohong Siwu Decoction, and 32 of which involved 221 related targets and 286 related diseases. Ferulic acid, kaempferol, quercetin, paeonol, paeoniflorin, ligustilide and caffeic acid can match more targets. It was predicted that the diseases treated by Taohong Siwu Decoction mainly included three categories:cancer related diseases (breast cancer, prostate cancer, etc.), cardiovascular diseases (hypertension, myocardial infarction, heart failure), and nervous system diseases; The key target proteins are RAC-α serine/threonine protein kinase (AKT1), serum albumin (ALB), and interleukin 17, vascular endothelial growth factor A, transcription factor AP-1, etc. KEGG signaling involved 165 pathways that promoted tumor cell apoptosis and inhibited tumor proliferation, immune regulation, blood circulation system regulation and endocrine regulation, etc. Conclusion The relationship between Taohong Siwu Decoction "component-target-pathway-disease" was established in this study, revealing the complex action mechanism of Taohong Siwu Decoction with multiple components and multiple targets to some extent. It provides a theoretical basis for the extensive clinical application of the classic prescription Taohong Siwu Decoction.
[中图分类号]
R285
[基金项目]
四川省科技计划项目(2020YFS0567);四川省教育厅高校科研创新团队项目(18TD0017);成都中医药大学“杏林学者”学科人才科研提升计划(CXTD2018018);四川省重点研发项目(2021YFS0256);四川省科技创新苗子工程培育及小发明小创造项目(2020094)