Integrated multi-target pharmacology of ginseng in acute myeloid leukemia through single-cell sequencing, molecular docking, network pharmacology, and in vitro experiments.

BACKGROUND: Acute myeloid leukemia (AML) is a heterogeneous disease of the hematological system. It is characterized by the rapid clonal expansion of abnormally differentiated myeloid progenitor cells within a complex microenvironment. Ginseng has shown anticancer effects in AML. However, the function and mechanism of the major active component of ginseng in AML still remain to be elucidated. This study aims to explore the potential therapeutic targets and molecular mechanisms of ginseng in the treatment of AML. METHODS: We analyzed 10 AML patients treated with the uniform chemotherapy regimen using single-cell RNA sequencing (scRNA-seq). Then, we identified potential targets of ginseng and AML through a combination of network pharmacology and experimental validation using public databases like TCMSP and CTD. After that, we performed protein–protein interaction, gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses to uncover the underlying mechanisms of ginseng in AML. Ultimately, we verified the network pharmacology results via in vitro experiments. RESULTS: Our results indicated that in non-complete remission (non-CR) AML patients, ginseng comprises 14 anti-AML active compounds and 34 related target genes. KEGG pathway analysis revealed that the AGE-RAGE and NF-κB signaling pathways may play a critical role in modulating chemoresistance in AML treatment. Through network pharmacology and molecular docking, we identified several active compounds in ginseng, including ginsenoside-Rh4, gomisin B, and panaxadiol, which demonstrated strong binding affinities toward core AML targets. In vitro experiments demonstrated that the combination of panaxadiol and Ara-C exhibited synergistic anti-leukemic effects. Further analysis indicated that panaxadiol potentiates the anti-leukemic activity of Ara-C. CONCLUSION: This study has elucidated the active compounds, potential targets, and signaling pathways of ginseng in overcoming AML chemoresistance. It offers new insights into the molecular mechanisms through which ginseng acts as a potential chemosensitizer of AML and lays a foundation for future research in this field. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12672-026-04747-1.