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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.

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