Objective To investigate the mechanisms by which ionizing radiation (IR) induces hematopoietic acute radiation syndrome (H-ARS) and to identify potential traditional Chinese medicinal treatments.

Methods We identified targets associated with IR and H-ARS, imported the overlapping targets into the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, analyzed and screened for key targets, and constructed a protein-protein interaction network. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to elucidate their biological significance. Bioactive compounds associated with the key targets of IR and H-ARS were collected to construct a key target–bioactive compound network, and the top 5 key targets ranked by degree were selected for molecular docking. Traditional Chinese medicines were screened based on bioactive compounds associated with the key targets of IR and H-ARS, and a key-target–bioactive compound–traditional Chinese medicine network was constructed. The "Four Properties and Five Flavors" and meridian tropism patterns of the screened traditional Chinese medicines were analyzed.

Results  A total of 338 overlapping targets were identified between IR and H-ARS, and GO and KEGG enrichment analyses yielded 1,658 and 177 entries, respectively. Through screening, 100 meaningful bioactive compounds were matched to 12 key targets. Seven bioactive compounds with a degree value ≥5 were used as small-molecule ligands for 35 molecular docking validation trials with the top 5 key targets ranked by degree value, yielding favorable results. Seventy meaningful bioactive compounds were matched to 269 traditional Chinese medicines. Among these, 47 traditional Chinese medicines had a "Degree" value ≥3; their properties were predominantly "warm" or "cold", their tastes were mostly "bitter" or "pungent", and they were primarily distributed among the lung, liver, and stomach meridians.

Conclusions The mechanism by which IR induces H-ARS may involve regulating the phosphoinositide 3-kinase-protein kinase B (PI3K-Akt) signaling pathway and other tumor-related signaling pathways, thereby interfering with key biological processes such as cell proliferation, cell growth, and transcriptional regulation, and inducing damage to hematopoietic stem and progenitor cells and disruption of the hematopoietic microenvironment. The screened bioactive compounds (such as resveratrol, curcumin, and magnolol) and traditional Chinese medicines herbs with high Degree values (such as Polygonum cuspidatum, Ephedra, and Glycyrrhiza) may exert radioprotective and hematopoietic repair effects by targeting key targets such as signal transduction and transcription activator 3 (STAT3), the tumor protein p53 (TP53), and the RAC-α serine/threonine protein kinase (AKT1). Molecular docking results confirm that the active compounds exhibit strong binding affinity for these key targets.