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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:Cancer cachexia is a multifactorial syndrome characterized by continuous body wasting and loss of skeletal muscle. Impaired mitochondria function is closely associated with muscle atrophy in cancer cachexia. Our previous study confirmed the effectiveness of Baoyuan Jiedu decoction (BJD) in inhibiting cancer-induced muscle atrophy in an in vivo model. However, little is known about its mechanisms in regulating mitochondria dysfunction. In this study, we evaluated the therapeutic effect and action mechanisms of BJD against atrophy both in the Lewis-conditioned medium induced C2C12 myotube atrophy model and in a BALB/c mice xenograft model using mouse colon cancer C26 cells. The mitochondrial content was tested by 10-Non-ylacridine orange staining. Expressions of related proteins and mRNAs were detected by western blotting (WB) and qPCR, respectively. As a result, 18 major components were identified in BJD by ultra-high performance liquid chromatography-quadrupole (UHPLC-Q) Exactive analysis. As shown in the in vitro results, BJD treatment prevented prominent myotube atrophy and increased the myotube diameter of C2C12 cells. Besides, BJD treatment increased mitochondrial content and ATPase activity. Furthermore, the protein and mRNA expressions that were related to mitochondrial functions and generation such as cytochrome-c oxidase IV, Cytochrome C, nuclear respiratory factor 1, and mitochondrial transcription factor A were significantly increased in BJD treatment compared to the control group. The in vivo results showed that BJD treatment prevented body weight loss and improved the gastrocnemius index in cachexia mice. Moreover, the expressions of Atrogin-1 and muscle RING-finger protein-1 were decreased by BJD treatment. Mechanically, BJD increased the expression of peroxisome proliferator-activated receptor-gamma coactivator 1, and consistently, inhibited the expression of p38 MAPK and its phosphorylation both in vivo and in vitro. Taken together, this study identified that BJD effectively relieved cancer-induced myotube atrophy and provided a potential mechanism for BJD in regulating mitochondrial dynamics through p38 MAPK/PGC-1α signaling pathway.

Dataset Information

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.

Similar Datasets

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