Holistic and dynamic metabolic alterations of traditional Chinese medicine syndrome in a toxic heat and blood stasis syndrome rat model

Abstract

Metabonomic analysis has been widely used in the study of traditional Chinese medicine (TCM) syndromes.In this paper, dynamic changes of the metabolic network during the evolution of a syndrome based on the toxic heat and blood stasis syndrome (THBSS) rat model have been elucidated for the first time. It was found that the metabolic trajectories could characterize three stages during THBSS evolution: the metabolic disturbance at 2-5 h, 8-12 h and 24-48 h could reflect the status of the excessive heat and little blood stasis stage, the coexistence of heat and blood stasis stage and the blood stasis stage respectively. The obtained dynamic metabolic network revealed the mechanism of THBSS progression: the inhibition of nicotinate and nicotinamide metabolism may lead to the activation of SIRT1 producing an inflammatory response, which then results in the disorder of energy metabolism and amino acid metabolism, and eventually the blood stasis appears. Nine involved metabolic pathways were found, among which the nicotinate and nicotinamide metabolism and histidine metabolism closely related to the occurrence of the inflammatory response in the early stage and blood stasis in the later stage of THBSS respectively.The former one, which is not reported in other blood stasis syndromes, might be the characteristic pathway of THBSS. This study firstly reveals the essence of THBSS progression, which is conducive to the diagnosis and pharmacotherapeutics of THBSS and related diseases, and also provides a new way to study TCM syndrome evolution.

Elucidation of the Mechanisms and Effective Substances of Paeoniae Radix Rubra Against Toxic Heat and Blood Stasis Syndrome With a Stage-Oriented Strategy

“…Additionally, glycine can generate serine, which can be converted into glucose for energy (Wheeler et al, 1999). We previously noted that energy is needed for the proliferation of inflammatory cells during this stage (Xu et al, 2017). Therefore, we considered that the elevation of glycine and serine in PRR-treated group A observed in the present study may be associated with preventing the expression of inflammatory cytokines.…”

“…injection of LPS (50 μg/kg). The time point of i. v. LPS administration was 0 h. In our previous study, we found that during 2-5 h, the rats were in the EHLBS stage and reached the BS stage after 24 h (Xu et al, 2017). Therefore, for the EHLBS-related studies, the freeze-dried PRR powder was dissolved in pure water and administered intragastrically (1.68 g/kg, at 10:00 a.m., once daily) to the rats in PRR-treated group A from the first day to the third day.…”

“…In our prior study, we found that in the EHLBS stage, the biochemical indexes of heat syndrome were significantly abnormal and the biochemical indexes of blood stasis syndrome were slightly abnormal in THBSS model rats. Whereas in the BS stage, THBSS model rats showed significantly abnormal biochemical indexes of blood stasis syndrome (Xu et al, 2017). Therefore, TNF-α, IL-6, forehead temperature, whole blood viscosities, and coagulation time (APTT, PT, and TT) were selected to evaluate the pharmacodynamic effects of PRR in EHLBS stage.…”

“…and energy metabolism (citrate cycle, pyruvate metabolism, etc.) were significantly disturbed during THBSS progression, which were closely related to the inflammation and hemorheology and coagulation abnormalities (the main manifestations in model rats during the progression of THBSS) (Xu et al, 2017). It is reported that bile acids are important signal molecules in energy metabolism and can affect coagulation through farnesol receptor X (Poland and Flynn 2021).…”

“…), elevated whole blood viscosity, and shortened prothrombin time, etc. (Xu et al, 2017). Based on these results, the present work aimed to elucidate the pharmacodynamic mechanisms and effective substances of PRR for the treatment of THBSS in LPS/CAR-induced THBSS rat model using a stage-oriented strategy.…”