Objective To analyze the similarity and difference of the mechanism for Guizhi decoction and its formula granules alleviating blood stasis syndrome (BSS) in rats using proton neclear magnetic resonance spectroscopy (¹H-NMR) metabolomics.

Methods Firstly, the chemical constituents of Guizhi decoction and its formula granules were analyzed based on liquid chromatography-mass spectrometry (LC-MS) technology. Secondly, 28 SD female mice were randomly divided into control group, model group, decoction group and granule group. The model was constructed with ice water bath and subcutaneous injection of adrenaline. After the modeling was completed, 24 h urine of rats was collected and metabolomic analysis was performed to reveal the metabolic profile regulation mechanism of BSS rats improved by Guizhi decoction and formula granules from the metabolomic level.

Results A total of 19 and 20 chemical constituents were identified in decoction and formula granules respectively, and 15 chemical constituents were identified together, 4 chemical constituents were identified in decoction but not in formula granules, and 5 chemical constituents were identified in formula granules but not in decoction. Compared with the model group, the index of whole blood viscosity was significantly regressed after drug intervention in the decoction group and the granule group, and the index of red blood cell aggregation was significantly regressed in the decoction group. The metabolomics results showed that 15 differential metabolites were screened in the decoction group compared with the model group, and that it could improve BSS by modulating four pathways: glycine, serine and threonine metabolism, glyoxylate and dicarboxylate metabolism, histidine metabolism, and taurine and hypotaurine metabolism. Thirteen differential metabolites were screened in the granule group compared with the model group. Guizhi formula granules could alleviate BSS by regulating three pathways: glycine, serine and threonine metabolism, glyoxylate and dicarboxylate metabolism and histidine metabolism.

Conclusion Both Guizhi decoction and formula granules can improve BSS by regressing disordered differential metabolites and metabolic pathways, which indicates that Guizhi formula granules have similar efficacy to the decoction.