Protective effects of oleanolic acid on B lymphocyte injury and exploring its mechanism base on network pharmacology
OBJECTIVE:This study evaluated the protective effect of oleanolic acid on cyclophosphamide-induced B lymphocyte injury in mice.METHODS:Kunming mice were given cyclophosphamide(80 mg/kg)per day to establish an immunosuppressive animal model.After modeling,oleanolic acid(25 mg/kg)was given per day for 28 days as the interventional group.At the same time,the model group and the blank group were set as controls.The percentage of bone marrow B lymphocyte subsets in each group was detected by flow cytometry.The chemical structure of oleanolic acid was obtained by PubChem database,and the drug target of oleanolic acid was predicted by the Swiss Target Prediction database.Analyses viathe protein interaction network,GO biological process enrichment and KEGG signal pathway enrichment of potential drug targets were carried out by the STRING platform.RESULTS:After administration of cyclophosphamide,the percentage of mature B cell subsets(IgD and B220 double positive cells)in the model group(2.585%±0.248%)was significantly lower than that in the blank group(8.235%±0.361%),while the percentage in the oleanolic acid interventional group(3.395%±0.445%)was significantly higher than that in the model group(P<0.01).Potential drug targets of oleanolic acid such as PTPN1 and CD81 were screened by the Swiss Target Prediction database.After SRTING platform analysis and Cytoscape remapping calculation,the top 5 node proteins in connectivity were PPARG,PTGS2,PPARA,MAPK3 and HMGCR.From the GO biological process enrichment and KEGG signaling pathway analyses,the pharmacological effects of oleanolic acid were enriched in biological processes such as negative regulation of lipid storage and B cell receptor signaling pathway.CONCLUSION:Oleanolic acid administration to mice increased the percentage of mature B cell subsets in bone marrow and enhanced the development of B lymphocytes by affecting the BCR signaling pathway.