Urinary metabolomics study the mechanism of Taohong Siwu Decoction intervention in acute blood stasis model rats based on liquid chromatography coupled to quadrupole time-of-flight mass spectrometry

Abstract

Taohong Siwu Decoction (TSD) is a classic prescription in traditional Chinese medicine and is widely used to promote blood circulation to remove blood stasis. However, the effect mechanisms are not yet well understood. Here, a urinary metabolomic approach based on liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (LC/Q-TOF-MS) was conducted to explore the changes in the endogenous metabolites and to assess the integral efficacy of TSD on acute blood stasis model rats. Then, parameters for hemorheology and coagulation functions were detected. Principal component analysis (PCA) and orthogonal partial least squares discriminate analysis (OPLS-DA) was used to investigate the global metabolite alterations and to evaluate the preventive effects of TSD in rats. Potential metabolite markers were found using OPLS-DA and t-test. Furthermore, metabolic pathway analysis was performed to construct metabolic networks. The results showed that TSD could significantly decrease whole blood viscosity and plasma viscosity. It also significantly prolonged partial thromboplastin time (APPT) and prothrombin time (PT), increased thrombin time (TT) and lowered fibrinogen content (FIB). Moreover, 24 potential metabolite markers of acute blood stasis were screened, and the levels were all reversed to different degrees after TSD administration. In metabolic networks, amino acid metabolism (arginine and proline metabolism; histidine metabolism; alanine, aspartate, and glutamate metabolism; phenylalanine, tyrosine, and tryptophan biosynthesis; phenylalanine metabolism) and lipid metabolism (glycerophospholipid metabolism; linoleic acid metabolism; alpha-linolenic acid metabolism) were closely related with the intervention mechanism of TSD on acute blood stasis. The urinary metabolomic approach can be applied to clarify the mechanism of TSD in promoting blood circulation to remove acute blood stasis and to provide the theoretical basis for further research on the therapeutic mechanism of TSD in clinical practice.