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

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          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, ChemMapper and STITCH databases were used to predict the protein targets of DBT. Using the Cytoscape 3.2.1 to establish a phyto-chemical 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 signalling pathways. DBT can promote iron ion binding and haemopoiesis activities, restrain inflammation, production of reactive oxygen, block apoptosis, and contribute significantly to the DBT treat anaemia.

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          Author and article information

          Chinese Journal of Natural Medicines
          20 April 2018
          : 17
          : 4
          : 275-290
          1 College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070,China
          Author notes
          *Corresponding author: HUA Yong-Li, Tel: 86-931-7631229; E-mail: huayongli 2004@ .

          These authors have no conflict of interest to declare.

          Copyright © 2019 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.
          Funded by: National Natural Science Foundation of China
          Award ID: 31560709
          Award ID: 31472234
          Funded by: College of Veterinary Medicine of Gansu Agricultural University
          Award ID: JYCX-KX005
          This work was supported by the National Natural Science Foundation of China (Nos. 31560709 and 31472234) and the College of Veterinary Medicine of Gansu Agricultural University (No. JYCX-KX005).


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