ABSTRACT
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), and blood deficiency(BD) (Cyclophosphamide (APH)-andCyclophosphamide(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 metaboliteswerescreened according to the multivariate statistical analysiscomparing the NC and BD groups, andthe 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 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 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.
Subject(s)
Animals , Anemia , Blood , Drug Therapy , Metabolism , Chromatography, Liquid , Cyclophosphamide , Toxicity , Disease Models, Animal , Drugs, Chinese Herbal , Chemistry , Pharmacology , Therapeutic Uses , Metabolic Networks and Pathways , Genetics , Metabolome , Metabolomics , Rats, Sprague-Dawley , Signal Transduction , Tandem Mass SpectrometryABSTRACT
The Chinese herbal Sophora alopecuroides is widely used to clean intestine and eliminate dampness, and it has good therapeutic effects on treating bacillary dysentery and inflammatory bowel disease, etc. in clinics. However, the mechanism of treatment is not yet well understood. The present study was aimed to explore the mechanism of Sophora alopecuroides treatment of large intestine dampness-heat syndrome (LIDHS). The LIDHS model was performed by the comprehensive factors, including high temperature and humidity environment, high-sugar and high-fat diet, and intraperitoneal injection of Escherichia coli. The blood routine, serum proinflammatory cytokine levels and histopathological changes of intestine were detected and observed. Meanwhile, the serum metabolomic approach was conducted using the method of ultra performance liquid chromatography coupled to quadrupole time-of-flight mass/mass spectrometry (UHPLC-Q/TOF-MS/MS). The results showed that Sophora alopecuroides has good therapeutic effects on the LIDHS rat models. After treatment with Sophora alopecuroides, the abnormality of blood routine indexes as well as proinflammatory cytokines, including IL-1β, IL-2, IL-6 and TNF-α in vivo, tended to be normal, and the histopathological changes of intestine were improved. Through metabolic profiling and protocol analysis, 9 potential metabolic markers may be closely related with the treatment mechanism of Sophora alopecuroides on this disease, including taurine, L-tryptophan, LysoPE, LysoPC, LPA, DG, chenodeoxycholic acid disulfate, traumatic acid and 7-ketodeoxycholic acid, which were involved in taurine and hypotaurine metabolism, glycerophospholipid metabolism, glycerolipid metabolism, tryptophan metabolism and primary bile acid biosynthesis etc. The serum metabolomic approach can be applied to clarify the therapeutic mechanism of Sophora alopecuroides on LIDHS, and provide the theoretical basis for Sophora alopecuroides in clinical practice.