Objective The mechanism of Danggui-Guizhi formula granules (DGK-GZK) in the intervention of cold coagulation and blood stasis syndrome (BSS) was studied based on ¹H-NMR fecal metabolomics.

Methods Eighteen SD female mice were randomly divided into three groups: control group, model group and DGK-GZK group. The effect of DGK-GZK on blood stasis was evaluated by weight changes and hemorheology indexes of rats. Meanwhile, fecal samples of rats in each group on the 14th day were collected for ¹H-NMR metabolomics analysis, so as to elucidate the pathogenesis of BSS and the regulation mechanism of DGK-GZK in the intervention of BSS from the metabolic level.

Results Compared with the model group, the weight loss of rats in the DGK-GZK group was slowed down after drug intervention, and the hemorheology was significantly reversed (P < 0.01). Fecal metabolomics results showed that the metabolic profile of the model group was significantly different from that of the control group on the 14th day, while the metabolic profile of the DGK-GZK group was separated from that of the model group and tended to be that of the control group. A total of fifteen biomarkers related to BSS were screened by multivariate statistical analysis, mainly involving pathways such as glycine, serine and threonine metabolism, alanine, aspartate and glutamate metabolism, butyric acid metabolism, as well as glyoxylic acid and dicarboxylic acid metabolism. DGK-GZK could significantly reverse these seven biomarkers: acetate, alanine, betaine, butyrate, leucine, propionate, and threonine (all P < 0.05), mainly regulating the disorders in pathways such as glycine, serine and threonine metabolism, alanine, aspartate and glutamate metabolism, butyric acid metabolism, as well as glyoxylic acid and dicarboxylic acid metabolism.

Conclusion BSS is a dynamic and slow-developing process, and the DGK-GZK can improve BSS by regulating various metabolites.