Baoyuan decoction alleviates myocardial infarction through the regulation of metabolic dysfunction and the mitochondria-dependent caspase-9/3 pathway

Supplemental Digital Content is available in the text Abstract Objective: Baoyuan decoction (BYD) is a traditional Chinese formula with myocardial protection efficacy validated by modern pharmacological tests. The present study aimed to investigate the effect and mechanism of BYD on alleviating myocardial infarction (MI). Methods: Nuclear magnetic resonance-based serum and urinary metabolomics were employed to explore the metabolic regulation effects of BYD in rats with MI induced by left anterior descending ligation. Oxygen-glucose deprivation/recovery (OGD/R) model in H9c2 cells and multiple molecular biology approaches were used to clarify the underlying action mechanisms of BYD. Results: BYD treatment recovered the serum and urinary metabolite profiles of the MI rats toward normal metabolic status and significantly improved mitochondrial energy metabolism and apoptosis pathways perturbed by MI. Analysis of the molecular mechanism of BYD indicated that it suppressed OGD/R-induced H9c2 cell apoptosis in a concentration-dependent manner by inhibiting the mitochondria-dependent caspase-9/3-poly ADP-ribose polymerase pathway. Conclusions: Our results demonstrate that BYD protects against myocardial apoptosis via the mitochondrial metabolic and apoptosis pathways. They also provide novel insights into the clinical application of BYD for the treatment of ischemic heart diseases.