Multi-omics analysis reveals that Danggui Buxue decoction ameliorates benzene-induced blood deficiency syndrome via the restoration of hematopoietic lineage and remodeling of the immune microenvironment

Blood deficiency syndrome (BDS) is a systemic disorder characterized by hematopoietic dysfunction and immune dysregulation. Given the limitations of current therapies, such as single efficacy and adverse effects, there is an urgent need for multitarget therapeutic agents with systemic regulatory effects. In this study, a mouse model of BDS was established through chronic benzene inhalation. Using an integrated transcriptomics and proteomics approach, we systematically investigated the therapeutic mechanism of Danggui Buxue Decoction (DBD). The results demonstrated that DBD significantly restored body weight, thymic and splenic indices, and bone marrow microstructure in model mice but also improved peripheral blood parameters such as the red blood cell count and mean corpuscular volume. Furthermore, DBD coordinately modulated serum hematopoietic factor and inflammatory cytokine levels. Mechanistically, DBD exerts its therapeutic effects through dual pathways. On the one hand, it promotes hematopoietic repair by upregulating transferrin receptor (TFRC) to support iron-dependent erythropoiesis, modulating KITLG/FLT3LG to maintain stem cell pool stability, and reprogramming integrin expression (e.g., upregulating ITGA4 and downregulating ITGA1) to facilitate stem cell homing and suppress fibrosis. On the other hand, it reshapes the immune microenvironment by enhancing MHC class II antigen presentation (e.g., H2Aa, H2-Ab1, H2-DMb1, and H2-Eb1) and immune cell activation (e.g., CD22, CD37, CD20, and CD8a), thereby reestablishing immune homeostasis. This study provides a systematic molecular basis for the multitarget and holistic regulatory properties of DBD, supporting its clinical application and suggesting potential therapeutic targets for BDS-related disorders.