Combining Gut Microbiota Data with Network Pharmacology to Explore the Mechanism of Danggui Sini Decoction Action Against Blood Stasis Syndrome in Rats

Abstract

Danggui Sini decoction is a traditional Chinese medicine preparation commonly used in the treatment of blood stasis syndrome through a mechanism yet to be defined. Therefore, we have explored its mechanism of action by combining pharmacology and gut microbiota analysis. To this end, female Sprague-Dawley rats were divided into 5 groups, including the control group, the acute blood stasis group, the Danshen tablet-treated group, the low-dose Danggui Sini decoction group, and the high-dose Danggui Sini decoction group. Danggui Sini decoction led to a significant reduction in the changes in the whole blood viscosity and plasma viscosity of rats with acute blood stasis syndrome, improved the coagulation function and cardiopulmonary pathological injury, upregulated the plasma 6-keto prostaglandin F1α and endothelial nitric oxide synthase, and downregulated thromboxane B2 and endothelin-1. The high throughput 16S rRNA gene sequencing results showed that Danggui Sini decoction reduced the number of pathogenic proteobacteria, significantly reduced erysipelas and suzericella, and increased the beneficial bacteria Roche, effectively improving the status of intestinal flora disorder in acute blood stasis rats. The Spearman correlation analyses showed that there was a close correlation between intestinal flora distribution and changes in blood stasis-related biochemical indices. In addition, network pharmacological analysis showed that the epidermal growth factor receptor, tumor protein p53, signal transducer and activator of transcription 3, vascular endothelial growth factor A, and hypoxia-inducible factor 1-alpha were the core targets of Danggui Sini decoction in alleviation of blood stasis. Further genetic ontological and pathway enrichment analyses suggested that the therapeutic effect of Danggui Sini decoction on blood stasis involved the lipid and atherosclerosis pathways, advanced glycation end-product-receptor for advanced glycation end-product signaling pathways in diabetic complications, fluid shear stress and atherosclerosis pathways, and hypoxia-inducible factors, 1-alpha signaling pathway, phosphatidylinositol 3-kinase- protein kinase B signaling, and other pathways. These results are helpful in understanding the mechanism by which Danggui Sini decoction improves blood stasis and provide a reference for further research.