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

代谢组学 汤剂 药理学 中医药 医学 代谢物 心力衰竭 甘油磷脂 机制(生物学) 化学 传统医学 生物信息学 生物化学 内科学 生物 病理 哲学 磷脂 替代医学 认识论
作者
Xu Wang,Yanhua Gao,Yuhuan Tian,Xin Liu,Guanhua Zhang,Qi Wang,Wenyu Xie,Kun Liu,Qi Qian,Qiao Wang
出处
期刊:Journal of Ethnopharmacology [Elsevier]
卷期号:250: 112397-112397 被引量:37
标识
DOI:10.1016/j.jep.2019.112397
摘要

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. 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. 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. 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. 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.
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