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

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.

Key words： Baoyuan decoction; Caspase-9/3 pathway; Mechanisms; Metabolomics; Mitochondrial energy metabolism; Myocardial infarction

Conflict of interest statement

The authors declare no conflict of interest.

Funding

This work was financially supported by the National Natural Sciences Foundation of China (Nos. 81530097 and 81222051) and the National Key Technology R&D Program “New Drug Innovation” of China (No. 2017ZX09101003-008-003).

Author contributions

Yong Jiang, Kewu Zeng, and Pengfei Tu designed the research. Zhiyong Du, Zeliu Shu, and Chun Li performed animal experiments and conducted metabolomics and molecular mechanism studies. Xiaoli Ma and Jun Li performed the chemical analysis of BYD. Xiaomin Song and Lixi Liao assisted with the molecular mechanism study. Zhiyong Du and Zeliu Shu wrote the article. Yong Jiang and Kewu Zeng revised and finalized the article. All authors read and approved the final manuscript. All data were generated in-house and no paper mill was used. All authors agreed to be accountable for all aspects of the work and ensure its integrity and accuracy.

Ethical approval of studies and informed consent

All animal studies followed the relevant national legislation and were approved by the Animal Care Committee of Beijing University of Chinese Medicine (BUCM-4-2018001201-1014).

Acknowledgments

The authors thank Acupuncture and Herbal Medicine for its assistance with scientific English in this manuscript, and acknowledge the technical help from the platform of State Key Laboratory of Natural and Biomimetic Drugs, Peking University.

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