Against radiation‐induced myelosuppression with Danggui Buxue Decoction: unraveling key pathways through network analysis and biological assays

BACKGROUND: Radiotherapy often causes radiation-induced myelosuppression, adversely affecting patient health and treatment outcomes. Danggui Buxue Decoction (DBD), a traditional Chinese Medicine formula, has shown potential in alleviating X-ray-induced myelosuppression (X-IM) and promoting hematopoietic recovery, though its specific targets and mechanisms remain unclear. This study seeks to clarify DBD's targets and mechanisms in combating X-IM using bioinformatics and experimental methods. RESULTS: Network pharmacology was employed to identify 153 key targets of DBD for treating X-IM. Gene ontology enrichment analysis highlighted critical biological processes, cellular components, and molecular functions, including nucleus, cytoplasm, protein binding, and DNA binding. KEGG/DAVID analysis underscored the pivotal role of the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway in DBD's protective effects against X-IM. Molecular docking validated the interaction of DBD's main components with core targets. The high-performance liquid chromatographic fingerprint analysis of DBD revealed distinct and reproducible peaks, indicating that its quality is controllable. Further content detection and component identification of calycosin and ferulic acid showed that the contents of key ingredients in DBD and their identities fully met the established requirements. Animal experiments demonstrated that DBD significantly accelerated the recovery of white blood cells, red blood cells, and platelets in X-IM-exposed mice, enhanced the secretion of hematopoietic factors like erythropoietin and granulocyte-macrophage colony-stimulating factor, and improved bone marrow cellularity and cell arrangement in the femurs of treated mice, as revealed by histopathological examination. Molecular analyses further confirmed that DBD significantly upregulated the mRNA expression of PI3K and AKT, consistent with the predictions from network pharmacology. The research employed a comprehensive strategy to explore the benefits and underlying mechanisms of DBD in addressing X-IM, ultimately laying a fresh groundwork for identifying and advancing natural therapeutic agents. © 2026 Society of Chemical Industry.