Drug Design, Development and Therapy (Sep 2022)
Network Pharmacology-Based Combined with Experimental Validation Study to Explore the Underlying Mechanism of Agrimonia pilosa Ledeb. Extract in Treating Acute Myocardial Infarction
Abstract
Muqing Zhang,1,2,* Jian Chen,3,4,* Yanwei Wang,2 Guobin Kang,2 Yixin Zhang,3,4 Xue Han3,4 1College of Integrative Medicine, Hebei University of Chinese Medicine, Shijiazhuang, People’s Republic of China; 2Affiliated Hospital, Hebei University of Chinese Medicine, Shijiazhuang, People’s Republic of China; 3School of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang, People’s Republic of China; 4International Joint Research Center on Resource Utilization and Quality Evaluation of Traditional Chinese Medicine, Shijiazhuang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yixin Zhang; Xue Han, Tel +86 311 89926316, Fax +86 311 89926316, Email [email protected]; [email protected]: 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
