A novel approach based on metabolomics coupled with network pharmacology to explain the effect mechanisms of Danggui Buxue Tang in anaemia  

作　　者：HUA Yong-Li MA Qi YUAN Zi-Wen ZHANG Xiao-Song YAO Wan-Ling JI Peng HU Jun-Jie WEI Yan-Ming 

机构地区：[1]College of Veterinary Medicine, Gansu Agricultural University

出　　处：《Chinese Journal of Natural Medicines》2019年第4期275-290,共16页中国天然药物（英文版）

基　　金：supported by the National Natural Science Foundation of China(Nos.31560709 and 31472234);the College of Veterinary Medicine of Gansu Agricultural University(No.JYCX-KX005)

摘　　要：Danggui Buxue Tang(DBT) is a famous Chinese medicinal decoction. Mechanism of DBT action is wide ranging and unclear. Exploring new ways of treatment with DBT is useful. Sprague–Dawley(SD) rats were randomly divided into 3 groups including control(NC, Saline), the DBT(at a dose of 8.10 g?kg–1), and blood deficiency(BD)(Cyclophosphamide(APH)-and Cyclophosphamide(CTX)-induced anaemia). A metabolomics approach using Liquid Chromatography-Quadrupole-Time-of-Flight/Mass Spectrometry(LC/Q-TOFMS) was developed to perform the plasma metabolic profiling analysis and differential metabolites were screened according to the multivariate statistical analysis comparing the NC and BD groups, and the hub metabolites were outliers with high scores of the centrality indices. Anaemia disease-related protein target and compound of DBT databases were constructed. The TCMSP, Chem Mapper and STITCH databases were used to predict the protein targets of DBT. Using the Cytoscape 3.2.1 to establish a phytochemical component–target protein interaction network and establish a component, protein and hub metabolite protein–protein interaction(PPI) network and merging the three PPI networks basing on BisoGenet. The gene enrichment analysis was used to analyse the relationship between proteins based on the relevant genetic similarity by ClueGO. The results shown DBT effectively treated anaemia in vivo. 11 metabolic pathways are involved in the therapeutic effect of DBT in vivo; S-adenosyl-L-methionine, glycine, L-cysteine, arachidonic acid(AA) and phosphatidylcholine(PC) were screened as hub metabolites in APH-and CTX-induced anaemia. A total of 288 targets were identified as major candidates for anaemia progression. The gene-set enrichment analysis revealed that the targets are involved in iron ion binding, haemopoiesis, reactive oxygen species production, inflammation and apoptosis. The results also showed that these targets were associated with iron ion binding, haemopoiesis, ROS production, apoptosis, inflammation and related signallDanggui Buxue Tang(DBT) is a famous Chinese medicinal decoction. Mechanism of DBT action is wide ranging and unclear. Exploring new ways of treatment with DBT is useful. Sprague–Dawley(SD) rats were randomly divided into 3 groups including control(NC, Saline), the DBT(at a dose of 8.10 g?kg–1), and blood deficiency(BD)(Cyclophosphamide(APH)-and Cyclophosphamide(CTX)-induced anaemia). A metabolomics approach using Liquid Chromatography-Quadrupole-Time-of-Flight/Mass Spectrometry(LC/Q-TOFMS) was developed to perform the plasma metabolic profiling analysis and differential metabolites were screened according to the multivariate statistical analysis comparing the NC and BD groups, and the hub metabolites were outliers with high scores of the centrality indices. Anaemia disease-related protein target and compound of DBT databases were constructed. The TCMSP, Chem Mapper and STITCH databases were used to predict the protein targets of DBT. Using the Cytoscape 3.2.1 to establish a phytochemical component–target protein interaction network and establish a component, protein and hub metabolite protein–protein interaction(PPI) network and merging the three PPI networks basing on BisoGenet. The gene enrichment analysis was used to analyse the relationship between proteins based on the relevant genetic similarity by ClueGO. The results shown DBT effectively treated anaemia in vivo. 11 metabolic pathways are involved in the therapeutic effect of DBT in vivo; S-adenosyl-L-methionine, glycine, L-cysteine, arachidonic acid(AA) and phosphatidylcholine(PC) were screened as hub metabolites in APH-and CTX-induced anaemia. A total of 288 targets were identified as major candidates for anaemia progression. The gene-set enrichment analysis revealed that the targets are involved in iron ion binding, haemopoiesis, reactive oxygen species production, inflammation and apoptosis. The results also showed that these targets were associated with iron ion binding, haemopoiesis, ROS production, apoptosis, inflammation and related signall

关 键 词：Danggui Buxue TANG Metabolomics NETWORK PHARMACOLOGY ANAEMIA 

分 类 号：R965[医药卫生—药理学]