Regulation on BCAAs catabolism pathway plays the key role in cyclophosphamide-induced leucopenia BALB/c mice after the treatment of a typical Traditional Chinese Medicine of Lvjiao Buxue Granules

Background: Cyclophosphamide is a common tumor chemotherapy drug used to treat various cancers, but the resulting immunosuppression leads to leukopenia, which is a serious limiting factor in clinical application. Therefore, the introduction of immunomodulators as adjuvant therapy may help to reduce the hematological side effects of cyclophosphamide. Lvjiao Buxue Granules has been widely used in clinical treatment of gynecological diseases such as anemia and irregular menstruation, and recently, it has been found to increase the role of white blood cells, but its mechanism of action is still unclear. In this research, we applied the 1H-NMR metabolomics approach to characterize metabolites in cyclophosphamide-induced leucopenia mice spleen, so as to fully understand the metabolic processes of leucopenia and improve the leukocyte function of Lvjiao Buxue Granules.Methods: Cyclophosphamide was used to establish the leucopenia mice with cancer chemotherapy and the content of white blood cells, red blood cells, hemoglobin, platelets, and other routine blood indexes were measured. The changes of endogenous metabolites in spleen analyzed by 1H-NMR metabolomics technique were investigated the regulation effect of LBG in mice with leukopenia. Afterward, the chemical components-targets-differential metabolites network of Lvjiao Buxue Granules was constructed by the use of biological targets network, thus leucopenia-relevant metabolism pathways were dissected. Results: The blood routine parameters and organ indexes levels of leucopenia mice with cancer chemotherapy were improved by Lvjiao Buxue Granules. The metabolomic study revealed that 15 endogenous metabolites in mice spleen were considered as potential biomarkers of Lvjiao Buxue Granules for its protective effect. Integrated analysis of metabolomics and biological targets network indicated that Lvjiao Buxue Granules exerted the leukocyte elevation activity by inhibiting the branched-chain amino acids (BCAAs) degradation pathway and increasing the levels of valine, leucine and isoleucine. Conclusion: Lvjiao Buxue Granules exert obvious efficacy on the mice model of leucopenia, which could be improved by regulating the branched-chain amino acid degradation pathway and the levels of valine, leucine and isoleucine.