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

Zhiyong Du, Zeliu Shu, Chun Li, Xiao-Min Song, Xiaoli Ma, Li-xi Liao, Jun Li, P. Tu, K. Zeng, Yong Jiang
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引用次数: 7

Abstract

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.
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保元汤通过调节代谢功能障碍及线粒体依赖性caspase-9/3通路缓解心肌梗死
摘要目的:保元汤是经现代药理试验证实具有心肌保护作用的中药传统方剂。本研究旨在探讨比亚迪对心肌梗死(MI)的缓解作用及其机制。方法:采用基于核磁共振的血清和尿液代谢组学方法,探讨比亚迪对左前降结扎致心肌梗死大鼠的代谢调节作用。利用H9c2细胞的氧葡萄糖剥夺/恢复(OGD/R)模型和多种分子生物学方法阐明比亚迪的潜在作用机制。结果:比亚迪使心肌梗死大鼠的血清和尿液代谢谱恢复到正常代谢状态,并显著改善心肌梗死扰乱的线粒体能量代谢和凋亡途径。通过分子机制分析,比亚迪通过抑制线粒体依赖的caspase-9/3-poly adp -核糖聚合酶途径,以浓度依赖的方式抑制OGD/ r诱导的H9c2细胞凋亡。结论:我们的研究结果表明,比亚迪通过线粒体代谢和细胞凋亡途径保护心肌细胞凋亡。他们也为比亚迪治疗缺血性心脏病的临床应用提供了新的见解。
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