A Metabolomics and Network Pharmacology Approach Using LC–MS to Investigate the Mechanisms of Fufang Ejiao Jiang in Treating Chemotherapy‐Induced Myelosuppression

OBJECTIVE: This study aimed to investigate the mechanism and pharmacologically active compounds of Fufang Ejiao Jiang (FFEJJ) in the prevention and treatment of myelosuppression after chemotherapy (MAC) through a combination of serum metabolomics and network pharmacology. METHODS: Sprague Dawley rats were randomly assigned to three groups: the blank group, the model group, and the FFEJJ group (10.8 g/kg). A MAC rat model was induced using cyclophosphamide. Simultaneously with model establishment, rats were intragastrically administered once daily for 15 consecutive days. The routine blood parameters of the rats were measured, and pathological changes in the spleen and bone marrow were observed. Nontargeted serum metabolomics was employed to identify differential metabolites associated with MAC and their related pathways. Liquid chromatography-mass spectrometry (LC-MS) was used to analyze the chemical composition of FFEJJ, and its mechanism and pharmacologically active compounds in the treatment of MAC were further predicted using network pharmacology. RESULTS: FFEJJ significantly improved the hematopoietic function of bone marrow in the MAC model rats. Compared to the blank group, the model group exhibited obvious spleen injury and bone marrow disorder, with noticeable fatty infiltration in the bone marrow cavity. Following FFEJJ treatment, the condition of spleen tissue and bone marrow in MAC rats was significantly improved. Serum metabolomics analysis of endogenous metabolites identified 14 differential metabolites associated with the MAC mechanism in both positive and negative ion modes, primarily involving pathways such as aminoacyl-tRNA biosynthesis, primary bile acid biosynthesis, and unsaturated fatty acid biosynthesis. Using LC-MS, 31 components were identified in FFEJJ. Network pharmacology predictions suggest that the potential pharmacologically active compounds of FFEJJ in the treatment of MAC include apigenin, oleanolic acid, maslinic acid, and azelaic acid. The underlying mechanism may be partly associated with the phosphatidylinositol 3-kinase/serine-threonine kinase (PI3K-Akt) signaling pathway. CONCLUSION: FFEJJ promotes hematopoietic recovery in MAC rats, likely by regulating endogenous metabolic disorders. Apigenin, oleanolic acid, maslinic acid, and azelaic acid are predicted to be multitarget active compounds, with PI3K-Akt signaling as a candidate pathway.