| Leukopenia is a decrease of the number of white blood cells,in which the total number of peripheral white blood cells continuously below 4.0×10~9/L.It leads to a decrease in immune function,secondary infection and seriously affects the prognosis process of patients.However,at present,there is no effective method and means for leukopenia caused by radiotherapy and chemotherapy.In recent years,traditional Chinese medicine formulas which have been proven to promote hematopoietic stem cell recovery and improve hematopoietic microscopy,have been widely used to treat leukopenia.On the other hand,traditional Chinese medicine formulas can also regulate the immune dysfunction and have significant effects on improving the success rate of treatment of cancer patients after radiotherapy and chemotherapy,improving their quality of life and prolonging life.Qi-Jing-Sheng-Bai granule(QJSB)is an effective traditional Chinese medicine formula that has been widely used for the treatment of leukopenia post radiotherapy or chemotherapy.QJSB is composed of ten medicinal materials,including Astragalus membranaceus(Huangqi),Cervil Cornus Colla(Lujiaojiao),Panax quinquefolium(Xiyangshen),Epimedium brevicornum(Yinyanghuo),Angelica sinensis(Danggui),Polygonatum sibiricum(Huangjing),Eclipta pwstmta(Mohanlian),Lycium barbarum(Gouqi),Psoralea corylifolia(Buguzhi)and Spatholobus suberectus(Jixueteng)with a ratio of 6:1:2:3:2:2:3:2:2:6.With ten herb medicines above,QJSB shows significant clinical effects on the treatment of leukopenia post radiotherapy or chemotherapy.This study integrated transcriptomics,network pharmacology and metabolomics to reveal the possible mechanism of QJSB on leukopenia treatment.Firstly,we evaluated the effect of QJSB by constructing a cyclophosphamide-induced leukopenia model in mice.Then,at the genetic level,the molecular mechanism of QJSB were studied by RNA-seq.Based on the results of RNA-seq,we further assessed the effects of drugs on the network through Random Walk with Restart(RWR).Subsequently,blood metabolomics were performed on QJSB and we explored its possible mechanism at metabolic level.Finally,transcriptomics and metabolomics data were integrated to conduct a comprehensive systematic analysis of QJSB.The results showed that QJSB can significantly increase the number of peripheral blood leukocytes,platelets and nucleated bone marrow cells in mice,enhance cell viability,and promote colony formation of bone marrow mononuclear cells.At the same time,it also can reverse the disorder of the serum cytokines IL-6 and G-CSF.The study found that QJSB regulates a range of biological processes,such as hematopoietic lineages,maintaining cell homeostasis,lymphocyte differentiation,metabolic processes(including lipids metabolism,amino acids metabolism,and nucleotides metabolism),B cell receptor signaling pathway,T cell activation and NOD-like receptor signaling pathways.Therefore,QJSB may play a protective role in mice leukopenia by promoting cell proliferation and differentiation,regulating metabolic responses and regulating immune function.In summary,this study integrates transcriptomics,network pharmacology and metabolomics analysis for QJSB and provides scientific data support for revealing the action mechanism of QJSB.In addition,the overall analysis strategy established in this study provides a reference for other Chinese medicine formulas research. |
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