BACKGROUND: According to traditional Chinese medicine theory, acute myocardial infarction (AMI) is primarily associated with qi stagnation and blood stasis. Simiao Yong'an (SMYA) decoction is a well-known prescription that clears heat, detoxifies, and promotes blood circulation. SMYA has been used in the treatment of ischemic heart diseases (IHD). However, further analysis is required to clarify the specific mechanisms through which SMYA improves AMI and to determine its therapeutic effects at different time points during the acute phase of myocardial infarction. AIM OF THIS STUDY: This study is aimed at investigating the protective effects of SMYA against AMI at various time points and to explore its underlying mechanisms. MATERIALS AND METHODS: The active ingredients in SMYA were identified through ultraperformance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF/MS). An integrated in silico approach was employed to predict potential targets of these compounds, and target-pathway associations were established by aligning the data with relevant databases. A cardiac ischemia/reperfusion (I/R) model in rats was created by ligating the left coronary artery, inducing ischemia for 45 min, and allowing for 24 h of reperfusion. SMYA treatment was administered for 7 days. Cardiac function was evaluated at different time points during the acute phase of myocardial infarction using echocardiography. Serum biochemical indexes were measured using a biochemical kit, and western blotting (WB) was used to analyze AKT, p-AKT, PI3K, p-PI3K, BAX, Bcl-2, and caspase-3 proteins. RESULTS: UPLC-Q-TOF/MS identified 25 components in SMYA, which were considered potential effective ingredients. Network analysis identified 161 key targets and 167 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways associated with SMYA, with the PI3K-Akt pathway being notably prominent. Experimental validation demonstrated that SMYA significantly reduced the levels of creatine kinase isoenzyme (CK-MB) and lactate dehydrogenase (LDH) in serum and improved left ventricular ejection fraction (LVEF) and fractional shortening (FS) after myocardial I/R injury in rats. Additionally, SMYA reduced myocardial cell apoptosis and activated the PI3K-AKT pathway in a dose-dependent manner. Molecular docking confirmed binding between SMYA components and AKT/BCL-2. CONCLUSION: This study elucidates the mechanisms underlying AMI and the molecular action of SMYA. SMYA alleviates I/R-induced AMI in rats by activating the PI3K-AKT pathway, suggesting its potential as a therapeutic target for myocardial remodeling. The dose- and time-dependent protective effects of SMYA suggest that the PI3K-AKT pathway and its downstream target BCL-2 constitute promising therapeutic targets for novel interventions in AMI.
Fu et al. (Thu,) studied this question.