Purpose: Acute myocardial infarction (AMI) is a cardiovascular disease with a high fatality rate. In this study, we combined network pharmacology and experimental pharmacology and discovered the potential mechanism of action and the active ingredients of the lily, Tricyrtis maculata was discovered. The monomer compound with stronger activity was discovered through in vitro cell experiments.
Methods: Forty known compounds were isolated from T. maculata. Using TCMSP, Swiss Target Prediction, metaTarFisher, GeneCards and OMIM databases, targets of drug compositions and AMI-related genes were obtained, and the differential expression genes between AMI and normal tissues were extracted through the GEO database. Then, through an online mapping tool, the intersection genes were obtained to predict the possible effective components of T. maculata that can be used to treat AMI. The top five targets were selected for molecular docking via the protein–protein interaction (PPI) network to verify the binding activity between key compounds and target proteins. GO and KEGG enrichment analyses of the intersection genes were carried out with the program R to further screen key genes and effective compositions. On this basis, the compound with more optimal activity was screened and validated in vitro.
Results: In this study, 40 known monomer components were selected, and 1112 predicted genes, 1655 disease genes, 1425 differentially expressed genes, 1206 GO functions and 127 KEGG pathways were obtained. The results of molecular docking showed that the binding of MMP9 with drug components is stable. Through the comprehensive research of network pharmacology and experimental pharmacology, it was shown that T. maculata intervenes in the process of AMI through multicomponent, multitarget, and multichannel synergistic effects. It is speculated that the anti-AMI effect may be related to the regulation of the Akt/FoxO/BCl signaling pathway. Cellular experiments showed that nicotiflorin has satisfactory anti-inflammatory activity and endothelial protection and can reduce the release of nitric oxide (NO), an inflammatory medium after endothelial cell damage.
Conclusion: This study reveals the therapeutic effect and relative mechanism of extract of T. maculata extract on AMI. Analysis revealed that nicotiflorin from T. maculata is a compound with satisfactory anti-inflammatory activity and endothelial protection, which provides a new direction and treatment basis for further experimental exploration and clinical treatment.

Keywords: Tricyrtis maculata, nicotiflorin, network pharmacology, experimental pharmacology, GEO data mining

中文翻译：

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三叶草烟碱治疗急性心肌梗死的作用机制：从网络药理学到实验药理学

目的：急性心肌梗死（AMI）是一种致死率较高的心血管疾病。在本研究中，我们将网络药理学和实验药理学相结合，发现了百合的潜在作用机制，并发现了黄芪的有效成分。通过体外细胞实验发现了活性更强的单体化合物。
方法：从T. maculata中分离出 40 种已知化合物. 利用TCMSP、Swiss Target Prediction、metaTarFisher、GeneCards和OMIM数据库，获得药物成分靶点和AMI相关基因，并通过GEO数据库提取AMI与正常组织的差异表达基因。然后，通过在线作图工具，获得交叉基因以预测斑蝽可能的有效成分可用于治疗 AMI。通过蛋白质-蛋白质相互作用（PPI）网络选择前五个目标进行分子对接，以验证关键化合物与目标蛋白质之间的结合活性。使用程序R对交叉基因进行GO和KEGG富集分析，进一步筛选关键基因和有效成分。在此基础上，筛选出活性更佳的化合物并进行体外验证。
结果：本研究选取了40个已知单体成分，得到了1112个预测基因、1655个疾病基因、1425个差异表达基因、1206个GO功能和127个KEGG通路。分子对接结果表明MMP9与药物成分的结合是稳定的。通过网络药理学和实验药理学的综合研究表明，斑蝥通过多组分、多靶点、多通道的协同作用干预AMI过程。推测抗AMI作用可能与调节Akt/FoxO/BCl信号通路有关。细胞实验表明，烟花苷具有令人满意的抗炎活性和内皮保护作用，并能减少内皮细胞损伤后炎症介质一氧化氮 (NO) 的释放。
结论：本研究揭示了斑蝥提取物对AMI的治疗作用及相关机制。分析表明，T. maculata中的烟花苷是一种具有令人满意的抗炎活性和内皮保护作用的化合物，为进一步的实验探索和临床治疗提供了新的方向和治疗依据。

关键词： 三叶草，烟花苷，网络药理学，实验药理学，GEO数据挖掘