Metabolomics of Spleen-Yang deficiency syndrome and the therapeutic effect of Fuzi Lizhong pill on regulating endogenous metabolism

Ethnopharmacological relevance: Spleen-Yang deficiency (SYD) is one of the primary causes of many digestive diseases, such as ulcerative colitis (UC), and irritable bowel syndrome (IBS), but its endogenous metabolic characteristics are still unclear. Fuzi Lizhong pill (FLZP) is well-known for its powerful capacity for treating SYD; however, its mechanisms require further study. Aim of the study: Herein, our present study aimed to investigate the essence of SYD from the perspective of metabolomics, and tried to reveal the anti-SYD action mechanisms of FLZP. Materials and methods: Firstly, the compound factor modeling method with the principle of "indiscipline in diet + excessive fatigue + intragastric administration of Senna water extracts" was used to establish Sprague Dawley (SD) rats as SYD model. Then, the visceral index, motilin (MTL), malonaldehyde (MDA), Interleukin 1 alpha (IL-1 alpha), and Interleukin 6 (IL-6) levels were used to verify the anti-SYD effect of FLZP. In addition, serum samples were analyzed by UPLC-QE/MS metabolomics technique. Finally, the metabolic pathways associated with specific biomarkers were analyzed to research the possible mechanism underlying the action of FLZP. Results: The expression of MTL, MDA, IL-1 alpha, and IL-6 were regulated by FLZP, which suggested that it has relieved diarrhea and gastrointestinal motility disorder caused by SYD and had an anti-peroxidation, anti-inflammatory, and immune regulation effect. A total of 75 metabolites were found to be the potential biomarkers of SYD. Moreover, FLZP regulates 21 metabolites and 10 vital pathways including the tricarboxylic acid (TCA) cycle, sphingolipid metabolism, and histidine metabolism. Conclusion: SYD primarily causes disorders of amino acid metabolism, lipid metabolism, carbohydrate metabolism, metabolism of cofactors and vitamins, nucleotide metabolism, and translation. In addition, FLZP regulated carbohydrate, lipid, and amino acid metabolisms, gastrointestinal motility, digestive juice secretion, immune regulation, as well as antioxidant effects. Hence, FLZP had a good therapeutic effect on treatment of SYD. It might be a promising therapeutic agent for the treatment of SYD-related diseases.