This study aims to compare the effects and mechanisms of the standard decoction and formula granules of Paeoniae Radix Rubra in regulating the metabolism in the rat model of heat toxin and blood stasis. SD rats were randomized into control, model, standard decoction, and formula granules groups. After 14 days of administration, the rats in the latter three groups were subjected to subcutaneous injection with carrageenan and intraperitoneal injection with bacterial lipopolysaccharide for the modeling of heat toxin and blood stasis. The anal temperature, coagulation indexes, platelet aggregation(PAG), serum levels of thromboxane B_2(TXB_2), 6-ketone-prostaglondin F1α(6-keto-PGF1α), interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), von Willebrand factor(vWF), endothelial nitric oxide synthase(eNOS), and endothelin-1(ET-1) were measured. The metabolites in rat serum were identified by ultra-high performance liquid chromatography-quadrupole-time of flight mass spectrometry(UPLC-Q-TOF-MS). Multivariate statistical analysis was performed to screen the differential metabolites, which were then subjected to the KEGG pathway enrichment analysis. The results showed that the standard decoction and formula granules of Paeoniae Radix Rubra improved the state of model rats by lowering the body temperature, inhibiting inflammation, reducing PAG, delaying coagulation, and regulating the vascular function. The metabolomics analysis screened out 15 and 65 differential metabolites in the standard decoction and formula granules groups, respectively, compared with the model group. The enrichment analysis of the differential metabolites showed that the standard decoction of Paeoniae Radix Rubra exerted effects by affecting four key metabolic pathways: α-linolenic acid metabolism, primary bile acid biosynthesis, linoleic acid metabolism, and phenylalanine metabolism. The formula granules of Paeoniae Radix Rubra exerted effects by affecting four key metabolic pathways: α-linolenic acid metabolism, citrate cycle(tricarboxylic acid cycle), purine metabolism, and glyoxylic acid and dicarboxylic acid metabolism. This study indicated that the standard decoction and formula granules of Paeoniae Radix Rubra had similar effects on the syndrome of heat toxin and blood stasis and both of them regulated α-linolenic acid catabolism, which provided a scientific basis for the clinical application of the formula granules of Paeoniae Radix Rubra.
Keywords: Paeoniae Radix Rubra; formula granules; metabolomics; standard decoction; syndrome of heat toxin and blood stasis.