Xu Wang1, Yanhua Gao1, Yuhuan Tian1, Xin Liu1, Guanhua Zhang1, Qi Wang1, Wenyu Xie1, Kun Liu1, Qi Qian1, Qiao Wang2. 1. Department of Pharmaceutical Analysis, School of Pharmacy, Hebei Medical University, Shijiazhuang, PR China. 2. Department of Pharmaceutical Analysis, School of Pharmacy, Hebei Medical University, Shijiazhuang, PR China. Electronic address: qiaowang88@hotmail.com.
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.
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.
Authors: Jia-Ying Qi; Ya-Kun Yang; Chuan Jiang; Yang Zhao; Yong-Chao Wu; Xue Han; Xuan Jing; Zhong-Lin Wu; Li Chu Journal: Front Cardiovasc Med Date: 2022-02-28