当前位置： SCI文献检索 > JOURNAL OF ETHNOPHARMACOLOGY期刊下所有文献 > Integrative serum metabolomics and network analysis on mechanisms exploration of Ling-Gui-Zhu-Gan Decoction on doxorubicin-induced heart failure mice.

Integrative serum metabolomics and network analysis on mechanisms exploration of Ling-Gui-Zhu-Gan Decoction on doxorubicin-induced heart failure mice.

Abstract：

ETHNOPHARMACOLOGICAL RELEVANCE:Ling-Gui-Zhu-Gan Decoction (LGZGD) formula, derived from traditional Chinese medicine (TCM), has definitive clinical efficacy in the treatment of heart failure (HF) in China. However, little is known of the underlying mechanism of LGZGD. AIM OF THE STUDY:The aim of this work was to investigate the therapeutic mechanism of LGZGD on HF treatment based on an integration of the serum metabolomics and network analysis. MATERIALS AND METHODS:HF model mice were established by intraperitoneal injecting of doxorubicin. Body weight, echocardiography, biochemical assay and hematoxylin and eosin staining experiments were used to evaluate the efficacy of LGZGD. A metabolomics approach based on ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) was performed to analyze the serum biomarkers from model group, control group and LGZGD-treatment group. Principle component analysis (PCA) and orthogonal projection to latent structures-discriminant analysis (OPLS-DA) were utilized to identify differences of metabolic profiles in mice among the three groups. The network of "gene-enzyme-metabolite" was built to investigate the possible mechanism of LGZGD from the systematic perspective. RESULTS:54 metabolites, which showed a significantly restoring trend from HF to normal condition, were regarded as potential biomarkers of LGZGD treatment. The most critical pathway was glycerophospholipid metabolism and arachidonic acid metabolism. According to the results of network analysis, 8 biomarkers were regarded as hub metabolites, which meant these metabolites may have a major relationship with the LGZGD therapeutic effects for the HF. 8 enzymes and 29 genes in the network were considered as potential targets of LGZGD treatment. CONCLUSIONS:By integrated serum metabolomic and network analysis, we found that LGZGD might retard the pathological process of HF by regulating the disturbed metabolic pathways and the relative enzymes, which may be potential mechanism for LGZGD in the treatment of HF.

journal_name

J Ethnopharmacol

journal_title

Journal of ethnopharmacology

authors

Wang X,Gao Y,Tian Y,Liu X,Zhang G,Wang Q,Xie W,Liu K,Qian Q,Wang Q

doi

10.1016/j.jep.2019.112397

subject

Has Abstract

pub_date

2020-03-25 00:00:00

pages

112397

eissn

0378-8741

issn

1872-7573

pii

S0378-8741(19)32454-7

journal_volume

250

pub_type

杂志文章

在线工具

Integrative serum metabolomics and network analysis on mechanisms exploration of Ling-Gui-Zhu-Gan Decoction on doxorubicin-induced heart failure mice.