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

ABSTRACT: 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.

SUBMITTER: Du Z

PROVIDER: S-EPMC5974172 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Integration of Metabonomics and Transcriptomics Reveals the Therapeutic Effects and Mechanisms of <i>Baoyuan</i> Decoction for Myocardial Ischemia.

Du Zhiyong Z Shu Zeliu Z Lei Wei W Li Chun C Zeng Kewu K Guo Xiaoyu X Zhao Mingbo M Tu Pengfei P Jiang Yong Y

Frontiers in pharmacology 20180523

Myocardial ischemia (MI) is an escalating public health care burden worldwide. <i>Baoyuan</i> 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 coronar ...[more]

PMID: 29875658

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Project description:ObjectiveModified Si-Miao-Yong-An decoction (MSMYA) was empirically originated from Si-Miao-Yong-An Decoction, which has been utilized for centuries to treat vasculopathy as well as heart diseases through clearing heat and detoxifying. This study aimed at confirming MSMYA's therapeutic effects for treating myocardial ischemia/reperfusion (I/R) injury and its underlying mechanisms.MethodsRats were intragastrically administered with MSMYA for 4 weeks after ischemia/reperfusion (I/R) operation. Superoxide dismutase (SOD) and malondialdehyde (MDA) concentration were determined by calorimetry. Coagulation function was determined using an automated coagulation analyzer. Levels of cysteinyl aspartate specific proteinase (caspase)-1, interleukin (IL)-1β, interleukin (IL)-18, and lactate dehydrogenase (LDH) were measured by an enzyme-linked immunosorbent assay (ELISA). Infarct size was determined by triphenyltetrazolium chloride (TTC) staining. Myocardial histopathological and ultrastructure changes were examined by H&E staining and electron microscopy, respectively. Relative mRNA expression of NLRP3, an apoptosis-associated speck-like proteins containing the caspase activation and recruitment domain (ASC), caspase-1, IL-1β, and IL-18 were analyzed using quantitative real-time polymerase chain reaction (PCR). Meanwhile, their relative protein expressions were measured using western blotting.ResultsThe results showed MSMYA can inhibit oxidative stress by increasing SOD and reducing MDA, suppress inflammatory reaction by decreasing NLRP3 inflammasome-related cytokines' level, improve coagulation function by increasing prothrombin time (PT) and activating partial thromboplastin time (APTT), and ameliorate myocardial histopathological and ultrastructural changes. In addition, MSMYA's cardioprotective effects probably related to suppressing NLRP3 inflammasome pathway activation by reducing NLRP3 inflammasome molecular mRNA and protein relative expression.ConclusionThe results indicated that MSMYA played an important role in protecting the myocardium from I/R injury. The likely mechanism is the inhibition of oxidative stress, improvement of cardiac injury, and the reduction of NLRP3-related inflammatory cytokines release. This provides a basis for further research on the mechanism and clinical application of MSMYA to improve myocardial I/R injury.

Project description:Background: Myocardial bridges (MBs) are prevalent and can be associated with acute and chronic ischemic syndromes. We sought to determine the substrates for ischemia in patients with angina, nonobstructive coronary arteries (ANOCA) and a MB in the left anterior descending artery. Methods: Patients with ANOCA underwent acquisition of intracoronary pressure and flow during rest, supine bicycle exercise and adenosine infusion. Coronary wave intensity analysis was performed, with perfusion efficiency defined as accelerating wave energy/total wave energy (%). Epicardial endothelial dysfunction was defined as a reduction in epicardial vessel diameter ≥20% in response to intracoronary acetylcholine infusion. Patients with ANOCA and a MB were compared to two ANOCA groups with no MB: one with coronary microvascular disease (CMD: coronary flow reserve, CFR, <2.5) and one with normal CFR (reference: CFR≥2.5). Results: 92 patients were enrolled in the study (30 MB, 33 CMD and 29 reference). FFR in these three groups was 0.86±0.05, 0.92±0.04 and 0.94±0.05; CFR was 2.5±0.5, 2.0±0.3 and 3.2±0.6. Perfusion efficiency increased numerically during exercise in the reference group (65±9% to 69±13%, p=0.063), but decreased in the CMD (68±10% to 50±10%, p<0.001) and MB (66±9% to 55±9%, p<0.001) groups. The reduction in perfusion efficiency had distinct causes: in CMD this was driven by microcirculation derived energy in early diastole, whereas in MB this was driven by diminished accelerating wave energy, due to the upstream bridge, in early systole. Epicardial endothelial dysfunction was more common in the MB group (54% versus 29% reference and 38% CMD). Overall, 93% of patients with a MB had an identifiable ischemic substrate. Conclusions: MBs led to impaired coronary perfusion efficiency during exercise, which was due to diminished accelerating wave energy in early systole compared to the reference group. Additionally, there was a high prevalence of endothelial and microvascular dysfunction. These ischemic mechanisms may represent distinct treatment targets.

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

Publications

Integration of Metabonomics and Transcriptomics Reveals the Therapeutic Effects and Mechanisms of <i>Baoyuan</i> Decoction for Myocardial Ischemia.

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