Abstract: BACKGROUND: Atractylenolide III can inhibit inflammatory response and cardiomyocyte apoptosis, exerting a cardioprotective effect, but its regulatory mechanism remains unclear.
OBJECTIVE: To investigate the protective effect of atractylenolide III on myocardial injury in a mouse model of myocardial infarction based on the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway.
METHODS: Sixty 8-week-old male C57BL/6 mice were selected and randomly divided into sham operation group, model group, low-, medium-, and high-dose atractylenolide III groups, and aspirin group, with 10 mice in each group. Myocardial infarction was induced by ligation of the left anterior descending coronary artery. One week after modeling, the low-, medium-, and high-dose atractylenolide III groups were administered atractylenolide III 5, 30, 60 mg/kg by gavage, respectively, and the aspirin group was administered 25 mg/kg aspirin by gavage, once daily for 4 weeks. Echocardiography was used to detect ventricular function indicators. Hematoxylin-eosin staining was used to observe myocardial histopathological changes and determine the optimal dose of atractylenolide III. TTC staining was used to observe myocardial infarct size. ELISA was used to detect serum myocardial injury markers and inflammatory factor levels. TUNEL staining was used to detect cell apoptosis. Western blot and qPCR were used to observe the expression of phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway-related proteins and mRNAs.
RESULTS AND CONCLUSION: (1) Compared with the model group, the ventricular function indicators improved significantly in the atractylenolide III groups and the aspirin group (P < 0.05). (2) Atractylenolide III ameliorated myocardial histopathological changes in mice, with the most significant effect observed in the high-dose atractylenolide III group. (3) Compared with the sham operation group, the model group showed increased percentage of myocardial infarct size (P < 0.05), higher levels of myocardial injury markers and inflammatory factors (P < 0.05), higher cardiomyocyte apoptosis rate (P < 0.05), and increased expression of phosphorylated phosphatidylinositol 3-kinase/phosphatidylinositol 3-kinase, phosphorylated protein kinase B/protein kinase B, phosphorylated mammalian target of rapamycin/mammalian target of rapamycin, as well as mRNA expression of phosphatidylinositol 3-kinase, protein kinase B, and mammalian target of rapamycin in myocardial tissue (P < 0.05). (4) Compared with the model group, the high-dose atractylenolide III group and the aspirin group showed decreased percentage of myocardial infarct size (P < 0.05), lower levels of myocardial injury markers and inflammatory factors (P < 0.05), lower cardiomyocyte apoptosis rate (P < 0.05), and decreased expression of the above-mentioned signaling pathway-related proteins and mRNAs in myocardial tissue (P < 0.05). These findings indicate that atractylenolide III can ameliorate myocardial histopathological damage and inflammatory response, and its mechanism is related to the regulation of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway.

Key words: atractylenolide III, myocardial infarction, myocardial injury, phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), mammalian target of rapamycin (mTOR), signaling pathway, inflammatory response