Investigating the pharmacological basis and mechanisms of the anti-thrombotic effects of Paeoniae Radix Rubra, both pre- and post-stir-frying with rice wine

Paeoniae Radix Rubra (PRR) is a commonly used traditional Chinese medicine known for promoting blood circulation and alleviating pain. Stir-frying PRR with rice wine enhances its effectiveness in improving blood flow and resolving stasis. To explore the pharmacodynamic basis and mechanisms behind PRR’s anti-thrombotic effects—both pre- and post-stir-frying—a comprehensive approach combining pharmacological research, metabolomics, and chemistry was employed. Fraction inter-cross validation experiments, pharmacological assessments, and metabolomic analyses confirm the efficacy of the fraction separation process. Wine-stir-fried PRR (WPRR) shows superior blood activation compared to PRR. PRR mainly affects the TCA cycle and sphingolipid metabolism pathways through its small molecules, enhancing coagulation and fibrinolysis systems’ functionality. All the subdivided components of WPRR have anti-thrombotic effects, especially polysaccharides and oligosaccharides. WPRR improves thrombotic conditions in rat blood stasis by modulating arachidonic acid metabolism, TCA cycle, lipid status enhancement, and angiogenesis stimulation while regulating platelet adhesion and aggregation. In conclusion, compared with PRR, the main material basis for the blood-activating efficacy of WPRR has transformed from small molecule compounds to polysaccharide and oligosaccharide components. The action pathways of WPRR in exerting anti-thrombotic efficacy have increased. The polysaccharide components in WPRR might possess considerable potential for being developed into natural anti-thrombotic drugs.