Purpose: The network pharmacology approach and validation experiment were performed to investigate the potential mechanisms of Agrimonia pilosa Ledeb. (APL) extract against acute myocardial infarction (AMI).
Methods: The primary compounds of APL extract were identified by High-Performance Liquid Chromatography (HPLC) analysis. The intersecting targets of active compounds and AMI were determined via network pharmacology analysis. A mouse model of AMI was established by subcutaneous injection of isoproterenol (Iso). Mice were treated with APL extract by intragastric administration. We assessed the effects of APL extract on the electrocardiography (ECG), cardiac representative markers, representative indicators of oxidative stress, pathological changes, and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway, as well as apoptosis-related indicators in the mice.
Results: Five candidate compounds were identified in APL extract. Enrichment analyses indicated that APL extract could exert myocardial protective effects via the PI3K/Akt pathway. ST segment elevation and increased heart rate were obviously reversed in APL extract groups compared to Iso group. We also detected significant decreases in lactate dehydrogenase (LDH), creatine kinase (CK), creatine kinase MB (CK-MB), malondialdehyde (MDA), and reactive oxygen species (ROS), as well as a significant increase in superoxide dismutase activities (SOD) after APL extract treatment. In addition, APL extract markedly decreased the number of apoptotic cardiomyocytes after AMI. In the APL extract groups of AMI mice, there were increased expression levels of p-PI3K, p-Akt, and B-cell lymphoma-2 (Bcl-2) protein, and there were decreases in Bcl-2-associated X (Bax), cysteinyl aspartate-specific proteases-3 (caspase-3), and cleaved-caspase-3 protein expression levels, as well as the Bax/Bcl-2 ratio.
Conclusion: APL extract had a protective effect against Iso-induced AMI. APL extract could ameliorate AMI through antioxidant and anti-apoptosis actions which may be associated with the activation of the PI3K/Akt signaling pathway.

Keywords: acute myocardial infarction, APL extract, isoproterenol, oxidative stress, apoptosis, PI3K/Akt


中文翻译：

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基于网络药理学结合实验验证研究探索仙鹤草的潜在机制。提取物治疗急性心肌梗塞

目的：通过网络药理学方法和验证实验研究龙牙草的潜在作用机制。(APL) 提取物抗急性心肌梗塞 (AMI)。
方法：APL 提取物的主要化合物通过高效液相色谱 (HPLC) 分析进行鉴定。通过网络药理学分析确定活性化合物和AMI的交叉靶点。通过皮下注射异丙肾上腺素(Iso)建立AMI小鼠模型。通过胃内给药用APL提取物处理小鼠。我们评估了 APL 提取物对心电图 (ECG)、心脏代表性标志物、氧化应激代表性指标、病理变化和磷脂酰肌醇-3-激酶 (PI3K)/蛋白激酶 B (Akt) 信号通路以及细胞凋亡的影响小鼠的相关指标。
结果：在 APL 提取物中鉴定出五种候选化合物。富集分析表明，APL 提取物可通过 PI3K/Akt 通路发挥心肌保护作用。与 Iso 组相比，APL 提取物组的 ST 段抬高和心率增加明显逆转。我们还检测到乳酸脱氢酶 (LDH)、肌酸激酶 (CK)、肌酸激酶 MB (CK-MB)、丙二醛 (MDA) 和活性氧 (ROS) 显着降低，以及超氧化物歧化酶活性显着增加(SOD) APL 提取物处理后。此外，APL 提取物显着降低了 AMI 后凋亡心肌细胞的数量。在 AMI 小鼠的 APL 提取物组中，p-PI3K、p-Akt 和 B 细胞淋巴瘤-2 (Bcl-2) 蛋白的表达水平升高，Bcl-2 相关 X (Bax ),
结论： APL提取物对Iso诱导的AMI具有保护作用。APL 提取物可通过抗氧化和抗凋亡作用改善 AMI，这可能与 PI3K/Akt 信号通路的激活有关。

关键词：急性心肌梗死，APL 提取物，异丙肾上腺素，氧化应激，细胞凋亡，PI3K/Akt