Salvianolic acid A, salvianolic acid B, and Danshensu promote angiogenesis by enhancing glycolysis of endothelial cells during myocardial infarction treatment

ETHNOPHARMACOLOGICAL RELEVANCE: Myocardial infarction (MI), a leading cause of morbidity and mortality, may be treated by enhancing glycolysis in myocardial microvascular endothelial cells to promote angiogenesis. Salvia miltiorrhiza provides cardioprotection by modulating energy metabolism and angiogenesis. While our previous research identified an optimal proportion (OP) of its active components for myocardial protection, it remains unclear whether this mechanism involves the regulation of endothelial glycolysis to promote angiogenesis. AIM OF THE STUDY: To clarify the therapeutic mechanism by which OP exerts cardioprotective effects by promoting angiogenesis through the upregulation of myocardial endothelial glycolysis. MATERIALS AND METHODS: In this study, oxygen-glucose deprivation (OGD)-treated H9c2 cells were used to detect glycolysis levels, and OGD-treated short hairpin (sh)-6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase3 (PFKFB3) human umbilical vein endothelial cells (HUVECs), and MI C57BL/6 mice were used to detect glycolysis and angiogenesis. RESULTS: The results demonstrated that OP could increase glycolysis levels through adenosine 5'-monophosphate-activated protein kinase (AMPK)/PFKFB3, and then activate hypoxia-inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF)/VEGF receptor 2 (VEGFR2) to promote angiogenesis, improve myocardial histopathological morphology, attenuate myocardial fibrosis, reduce levels of myocardial enzymes, enhance cardiac function, and ultimately exert myocardial protective effects in MI mice. CONCLUSION: OP can enhance myocardial glycolysis through AMPK/PFKFB3, and then activate HIF-1α/VEGF/VEGFR2 to promote angiogenesis and serve as a therapy for MI. The preliminary elucidation of the efficacy and therapeutic mechanism of OP in MI provides a methodological basis for the clinical application and drug development of Salvia miltiorrhiza.