Data_Sheet_2_Integration of Metabonomics and Transcriptomics Reveals the Therapeutic Effects and Mechanisms of Baoyuan Decoction for Myocardial Ischemia.XLSX

Myocardial ischemia (MI) is an escalating public health care burden worldwide. Baoyuan decoction (BYD) is a traditional Chinese medicine formula with cardioprotective activity; however, its pharmacological characteristics and mechanisms are obscured. Herein, a multi-omics strategy via incorporating the metabonomics, transcriptomics, and pharmacodynamics was adopted to investigate the effects and molecular mechanisms of BYD for treating MI in a rat model of left anterior descending coronary artery (LADCA) ligation. The results indicated that BYD has a significantly cardioprotective role against MI by decreasing the infarct size, converting the echocardiographic abnormalities and myocardial enzyme markers, and reversing the serum metabolic disorders and myocardial transcriptional perturbations resulting from MI. Integrated bioinformatics analysis and literature reports constructed the interaction network based on the changes of the key MI targeted-metabolites and transcripts after BYD treatment and disclosed that the cardioprotection of BYD is mainly involved in the regulation of energy homeostasis, oxidative stress, apoptosis, inflammation, cardiac contractile dysfunction, and extracellular matrix remodeling. The results of histopathological examination, quantitative RT-PCR assay, cardiac energy synthesis, and serum antioxidant assessment complemented the multi-omics findings, and indicated the multi-pathway modulation mechanisms of BYD. Our investigation demonstrated that the multi-omics approach could achieve a complementary and verified view for the comprehensive evaluation of therapeutic effects and complex mechanisms of TCMF like BYD.

心肌缺血（Myocardial ischemia, MI）已成为全球日益加重的公共卫生医疗负担。保元汤（Baoyuan decoction, BYD）是一种具有心脏保护活性的传统中药方剂，但其药理特征与作用机制仍不明确。本研究采用整合代谢组学（metabonomics）、转录组学（transcriptomics）与药效学（pharmacodynamics）的多组学策略，在冠状动脉左前降支（left anterior descending coronary artery, LADCA）结扎构建的大鼠心肌缺血模型中，探究保元汤治疗心肌缺血的效应及其分子机制。研究结果显示，保元汤可通过缩小梗死面积、改善超声心动图异常与心肌酶标志物水平、逆转心肌缺血所致的血清代谢紊乱与心肌转录扰动，发挥显著的心肌保护作用。整合生物信息学分析结合文献报道，基于保元汤干预后关键心肌缺血靶向代谢物与转录本的变化构建了相互作用网络，揭示保元汤的心肌保护作用主要涉及能量稳态、氧化应激、细胞凋亡、炎症反应、心肌收缩功能障碍及细胞外基质重塑的调控。组织病理学检查、定量逆转录聚合酶链反应检测、心肌能量合成及血清抗氧化能力评估的结果进一步佐证了多组学研究发现，阐明了保元汤多通路调控的作用机制。本研究证实，多组学方法可为全面评价保元汤等中药方剂（Traditional Chinese Medicine Formula, TCMF）的治疗效应与复杂作用机制提供互补且经验证的研究视角。