Mechanisms of Danggui Buxue Tang on Hematopoiesis via Multiple Targets and Multiple Components: Metabonomics Combined with Database Mining Technology.

This study aimed to explore the mechanism of action of Danggui Buxue Tang (DBT) with its multiple components and targets in the synergistic regulation of hematopoiesis. Mouse models of hematopoiesis were established using antibiotics. Metabolomics was used to detect body metabolites and enriched pathways. The active ingredients, targets, and pathways of DBT were analyzed using system pharmacology. The results of metabolomics and system pharmacology were integrated to identify the key pathways and targets. A total of 515 metabolites were identified using metabolomics. After the action of antibiotics, 49 metabolites were markedly changed: 23 were increased, 26 were decreased, and 11 were significantly reversed after DBT administration. Pathway enrichment analysis showed that these 11 metabolites were related to bile secretion, cofactor biosynthesis, and fatty acid biosynthesis. The results of the pharmacological analysis showed that 616 targets were related to DBT-induced anemia, which were mainly enriched in biological processes, such as bile secretion, biosynthesis of cofactors, and cholesterol metabolism. Combined with the results of metabolomics and system pharmacology, we found that bile acid metabolism and biotin synthesis were the key pathways for DBT. Forty-two targets of DBT were related to these two metabolic pathways. PPI analysis revealed that the top 10 targets were CYP3A4, ABCG2, and UGT1A8. Twenty-one components interacted with these 10 targets. In one case, a target corresponds to multiple components, and a component corresponds to multiple targets. DBT acts on multiple targets of ABCG2, UGT1A8, and CYP3A4 through multiple components, affecting the biosynthesis of cofactors and bile secretion pathways to regulate hematopoiesis.

Gut microbiota affects the efficacy of Danggui Buxue Tang by affecting plasma concentration of active ingredients.

ETHNOPHARMACOLOGICAL RELEVANCE: Danggui Buxue Tang (DBT) is a traditional Chinese medicine, which has the function of supporting Qi and enriching blood. Antibiotics can cause Gut microbiota disorder and affect efficacy of DBT. AIM OF THE STUDY: Explore the manner in which Gut microbiota affects the efficacy of Danggui Buxue Tang. MATERIALS AND METHODS: In this study, antibiotics were used to destroy gut microbiota. The changes of DBT efficacy were detected to verify the effect of gut microbiota on DBT efficacy. The changes of gut microbiota was detected using 16S rRNA sequencing, and UPLC-MS/MS was used to analyze the plasma concentration of active ingredients. Correlation analysis was used to establish the relationship between gut microbiota, blood components and drug efficacy, and to explore the role of gut microbiota in the efficacy of DBT. RESULTS: The results showed that the efficacy in the DBT group was significantly improved compared with the control group (p<0.05). Compared with DBT group, the efficacy in antibiotic DBT treatment (ABXDBT) group was significantly reduced, 194 plasma metabolites and 18 DBT blood components were significantly altered in ABXDBT group, and 11 DBT blood components such as caffeic acid and formononetin were significantly decreased. Correlation analysis showed that 6 DBT blood components were related with the decrease of efficacy. Network pharmacology analysis showed that the above 6 DBT blood components participated in the hematopoietic regulation through PI3K-Akt and HIF-1 signaling pathways. Correlation analysis showed that Bacteroides and other intestinal bacteria were related to the absorption of DBT active ingredients. The drug metabolic pathway of gut microbiota was significantly decreased after antibiotic treatment (p = 0.033). CONCLUSIONS: Gut microbiota such as Bacteroides affects the efficacy of DBT by affecting the metabolism and absorption of DBT active ingredients such as caffeic acid and formononetin.