A novel approach based on metabolomics coupled with network pharmacology to explain the effect mechanisms of Danggui Buxue Tang in anaemia / 中国天然药物

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.

Sophora alopecuroides ameliorates large intestine dampness-heat syndrome in rats by serum metabolomic approach based on UHPLC-Q/TOF-MS/MS / 药学学报

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.

Effect of different processed volatile oils from Angelica sinensis on urinary metabolomics rats / 中国中药杂志

Different processed volatile oils from AS on urine metabolites of normal rats were analyzed to reveal the possible metabolic pathways. Totally 50 male Waster rats were randomly divided into normal control group, C-ASVO group, J-ASVO group, T-ASVO group and Y-ASVO group, with 10 rats in each group. The normal group was given isovolumetric 0.5% polyoxyethylene sorbitan fatty acid ester（Tween-80）, while the other groups were given 0.176 mL•kg⁻¹ different processed volatile oils from AS. Drugs were given for 3 successive days. The urine was collected at 48 h with metabolic cages. GC-MS was employed to detect the metabolic fingerprint of rat urine in different times. Principal component analysis(PCA) and orthogonal partial least-squares discriminant analysis(OPLS-DA) were adopted for a multivariate statistical analysis. Metabolites with potential differences were selected based on the results of variable importance in the projection(VIP) and t test. The metabolic pathway analysis(MetPA) database was built for different metabolites' metabolic pathways. The results showed that compared with the normal group, 31 kinds of endogenous metabolites in the different processed volatile oils from AS groups change significantly(P<0.05). And there were differences in normal rat urine metabolites among the different processed volatile oils from AS, of which the influence degree of J-ASVO was slightly stronger than C-ASVO, T-ASVO, and Y-ASVO. Therefore, the metabolism effect may be focused on energy metabolism, amino acid metabolism, fatty acid metabolism and glucose metabolism. This study focused on metabolism and mechanism of different processed volatile oils from AS, and provided new ideas for pharmacological actions of traditional Chinese medicines.

Metabolomic evaluation for anti-inflammatory effect of volatile oils from different preparations of Angelicae Sinensis Radix / 中国中药杂志

To evaluate the anti-acute inflammation effects of volatile oils from different processed products of Angelicae Sinensis Radix(AS) in the rat model of acute inflammation established by the metabolomic method. Volatile oil of charred AS (C-VOAS), wine-processed AS (J-VOAS), locally processed AS (T-VOAS) and oil-process AS (Y-VOAS) were applied to intervene the rat acute paw swelling inflammation model induced by Carrageenan. Changes in serum HIS, 5-HT, PGE2 and TNF-α content in rats were detected. Gas chromatography-mass spectrometry was used to detect the metabolites in plasma. Potential biomarkers were investigated according to principal component analysis method and partial least-squares discriminant analysis. According to the results, C-VOAS and J-VOAS could significantly inhibit inflammatory mediators Histamine, 5-hydroxytryptamine, prostaglandin-E2 and cytokine tumor necrosis factor-alpha (P<0.01), and T-VOAS and Y-VOAS also showed a significantly inhibitory effect (P<0.05). Compared with the normal group, 14 endogenous metabolite biomarkers showed metabolic disturbance in plasma (P<0.05 or P<0.01). Compared with acute inflammation model group, C-VOAS and J-VOAS could better recover the levels of the endogenous metabolites (P<0.05 or P<0.01) than T-VOAS and Y-VOAS (P<0.05 or P<0.01). This study suggests that C-VOAS and J-VOAS show a better anti-inflammatory effect than T-VOAS and Y-VOAS. Therefore, the metabolomic method could be used to expound the anti-inflammatory mechanism of volatile oils from different processed products of AS, and provide a theoretical basis for clinical application of VOAS.