OBJECTIVE  To explore the differences and the mechanisms of various fractions extracted from Angelicae Sinensis Radix (AS) and wine-processed Angelicae Sinensis Radix (WAS) on activating blood circulation based on network pharmacology and animal experiments validation.

  METHODS  Drug targets of AS and blood stasis (BS)-associated targets were screened from disease and drug related database, and the key targets and the core components were screened according to topological eigenvalues. Gene ontology (GO) function and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis were performed. The acute blood stasis model in rats induced by adrenaline hydrochloride and ice-water bath was used to explore the differences of various fractions extracted from AS and WAS. And then the screened targets based on network pharmacology were further verified.

  RESULTS  A total of 134 potential active components, 1 062 targets of AS, 476 BS-associated targets, 145 common targets, 15 key targets and 36 core components were obtained. Enrichment analysis showed that the key targets were mainly involved in biological processes such as vascular endothelial growth factor production, positive regulation of nitric oxide biosynthetic process and cellular response to hypoxia, as well as Vascular endothelial growth factor (VEGF) signaling pathway, Phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway, and Tumor necrosis factor (TNF) signaling pathway. The results of animal experiments showed that compared with the model group, the effect of activating circulation of n-butyl alcohol-soluble fraction from WAS (WASB) was superior to those of other fractions. WASB remarkably improved the histopathological manifestations and appearance morphological characteristics of the acute blood stasis model in rats, significantly reduced organ index, evidently inhibited the release of inflammatory mediators (Nitric oxide, NO; Prostaglandin E₂, PGE₂; Tumor necrosis factor-α, TNF-α), suppressed oxidative stress, and significantly restrained the expression of VEGFA and the phosphorylation of AKT and PI3K (P<0.05, 0.01, 0.001). The effects of various fractions extracted from WAS on activating blood circulation were superior to those of the same fractions of AS.

  CONCLUSION  The mechanisms of the enhanced effects from WAS on activating blood circulation may be related to down-regulation the expression levels of VEGFA, p-AKT and p-PI3K, inhibition of VEGF and PI3K/AKT signal pathways, decrease of pro-inflammatory mediator production (such as NO, PGE₂ and TNF-α), suppressing the production of MDA, and increasing the level of SOD to alleviate oxidative stress.