UPLC-Q-Exactive-based rats serum metabolomics for characterization of traditional Chinese medicine Natures and Flavors

ETHNOPHARMACOLOGY RELEVANT: "Four Natures and five "Flavors" comes from the high generalization of medicine pharmacological rules from clinical practice by ancients. "Flavor" and "Natures"are both descriptions of the effect properties of traditional Chinese medicine. At present, researchers have realized that the "Flavors" (Pungent, Sour, Sweet, Bitter and Salty) are related to the different pharmacological effects of treatment. The "Natures" (Warm, Hot, Cold and Cool) are closely related to energy and substance metabolism and contribute to the effect of the "Flavors". Since "Four Natures and five Flavors" are the rules derived from clinical practice, how to describe and characterize "Natures" and "Flavors" scientifically is still a problem that needs to be solved.the aim is to objectively further understand the scientific connotations of properties ("Flavors"and "Natures") from the perspective of metabolomics and characterize them by metabolites."Pungent-Neutral", "Sweet-Neutral and "Bitter-Neutral" TCMs were selected to characterize the "Flavors" (Pungent, Sweet and Bitter). "Pungent-Warm" and "Bitter-Cold" were selected to characterize the "Natures" (Warm and Cold). The rat serum metabolomics was performed on UHPLC-Q-Exactive. Metabolites were identified through the metabolites databases and related literature.The "Flavors" and "Natures" metabolites were identified, respectively, including four "Pungent", four "Sweet" and thirteen "Bitter" characterized metabolites and thirteen "Cold" and sixteen "Warm"related metabolites.The "Natures" characterized metabolites show the "Natures" are closely related to lipid and energy metabolism. The "Warm" may promote lipid metabolism to produce ATP to generate energy through bile acid metabolism and purine metabolism. The "Cold" may inhibit lipid metabolism to generate ATP to decrease energy through the way of tryptophan metabolism and purine metabolism. The "Flavors" characteristic metabolites can provide a theoretical basis for the rules of the "Flavors". These metabolites can also be used to characterize TCM's "Natures" and "Flavors" in the development of traditional Chinese medicine resources and quality control.