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基于网络药理学和分子对接的真武汤治疗心力衰竭的机制

Mechanism of Zhen Wu Decoction in the Treatment of Heart Failure Based on Network Pharmacology and Molecular Docking.

作者信息

Ma Chen-Yu, Ma Yu-Qian, Deng Min

机构信息

Cixi Third People's Hospital, Zhejiang, China.

Wenzhou Medical University, Wenzhou, China.

出版信息

Evid Based Complement Alternat Med. 2022 Mar 15;2022:4877920. doi: 10.1155/2022/4877920. eCollection 2022.

Abstract

Heart failure (HF) is a serious manifestation or advanced stage of various cardiovascular diseases, and its mortality and rehospitalization rate are still on the rise in China. Based on the network pharmacology method, 59 components of Zhen Wu decoction (ZWD) and 83 target genes related to HF were obtained. Through the PPI network, four potential therapeutic targets were identified: AKT1, IL6, JUN, and MAPK8. The beneficial components of ZWD might intervene HF through the AGE-RAGE signalling pathway in the diabetes component, fluid shear stress and atherosclerosis, the TNF signalling pathway, TB, and Kaposi sarcoma related herpesvirus infection, according to a KEGG enrichment study. The protein interaction network of candidate targets was constructed by the STRING database, and the protein interaction network was clustered by MEODE software. GO and KEGG enrichment analyses were performed on the core modules obtained by clustering. Finally, AutoDock Vina software was used for molecular docking verification of key targets and active ingredients. The result was that 75 active ingredients and 109 genes were screened as potential active ingredients and potential targets of Shengjie Tongyu decoction for CHF treatment. The main active components were quercetin, luteolin, kaempferol, dehydrated icariin, isorhamnetin, formononetin, and other flavonoids. Il-6, MAPK1, MAPK8, AKT1, VEGFA, and JUN were selected as the core targets. Molecular docking showed that the key components were well connected with the target. GO enrichment analysis showed that Shengjie Tongyu decoction could play a role through multiple biological pathways including angiogenesis, regulation of endothelial cell proliferation, binding of cytokine receptors, negative regulation of apoptotic signalling pathways, regulation of nitric oxide synthase activity, and reactive oxygen metabolism. Key pathways mainly focus on the toll-like receptor signalling pathway, nod-like receptor signalling pathway, MAPK signalling pathway, mTOR signalling pathway, JAK-STAT signalling pathway, VEGF signalling pathway, and other pathways. Through molecular docking technology, it was found that a variety of effective components in ZWD, such as kaempferol. Molecular docking technology has preliminatively verified the network pharmacology and laid a foundation for the follow-up pharmacological research.

摘要

心力衰竭(HF)是各种心血管疾病的严重表现或晚期阶段,在中国其死亡率和再住院率仍在上升。基于网络药理学方法,获得了真武汤(ZWD)的59种成分和与HF相关的83个靶基因。通过蛋白质-蛋白质相互作用(PPI)网络,确定了四个潜在治疗靶点:AKT1、IL6、JUN和MAPK8。根据京都基因与基因组百科全书(KEGG)富集研究,真武汤的有益成分可能通过糖尿病并发症中的晚期糖基化终末产物-受体(AGE-RAGE)信号通路、流体切应力与动脉粥样硬化、肿瘤坏死因子(TNF)信号通路、结核病以及卡波西肉瘤相关疱疹病毒感染来干预HF。通过STRING数据库构建候选靶点的蛋白质相互作用网络,并使用MEODE软件对蛋白质相互作用网络进行聚类。对聚类得到的核心模块进行基因本体(GO)和KEGG富集分析。最后,使用AutoDock Vina软件对关键靶点和活性成分进行分子对接验证。结果筛选出75种活性成分和109个基因作为升阶通瘀汤治疗慢性心力衰竭(CHF)的潜在活性成分和潜在靶点。主要活性成分是槲皮素、木犀草素、山柰酚、脱水淫羊藿苷、异鼠李素、芒柄花素及其他黄酮类化合物。选择白细胞介素-6(Il-6)、丝裂原活化蛋白激酶1(MAPK1)、丝裂原活化蛋白激酶8(MAPK8)、蛋白激酶B(AKT1)、血管内皮生长因子A(VEGFA)和JUN作为核心靶点。分子对接表明关键成分与靶点连接良好。GO富集分析表明升阶通瘀汤可通过多种生物学途径发挥作用,包括血管生成、内皮细胞增殖调控、细胞因子受体结合、凋亡信号通路的负调控、一氧化氮合酶活性调节和活性氧代谢。关键途径主要集中在Toll样受体信号通路、NOD样受体信号通路、MAPK信号通路、哺乳动物雷帕霉素靶蛋白(mTOR)信号通路、Janus激酶-信号转导及转录激活因子(JAK-STAT)信号通路、VEGF信号通路等。通过分子对接技术发现,真武汤中的多种有效成分,如山柰酚。分子对接技术初步验证了网络药理学,为后续的药理学研究奠定了基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63b0/8941561/6c76473de816/ECAM2022-4877920.001.jpg

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