Background: Acute myeloid leukemia (AML) is a heterogeneous disease. It is characterized by the rapid clonal expansion of abnormally differentiated myeloid progenitor cells within a complex microenvironment. Current treatment regimens mainly rely on chemotherapy. This emphasizes the necessity of exploring alternative therapeutic molecules or drugs to reduce chemoresistance in AML. Ginseng has shown anticancer effects in multiple tumors. However, the function and mechanism of panaxadiol, a major active component of ginseng, in AML still need to be clarified.

Methods: In this study, we first analyzed 10 acute myeloid leukemia (AML) patients treated with the same chemotherapy regimen using single-cell RNA sequencing (scRNA-seq). Subsequently, we compared the cellular composition between complete response (CR) and non-complete response (nCR) patients. Next, we screened for potential targets of ginseng and AML through a combination of cyberpharmacology and experimental validation using public databases like TCMSP and CTD. After that, we carried out protein-protein interaction (PPI), gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses to uncover ginseng's mechanism in AML. Finally, we verified the network pharmacology results via in vitro experiments.

Results: Our results indicated that in non-CR AML patients, within the AML cell population, the proportion of immature cells in the hematopoietic process increased significantly, while intercellular communication decreased. Ginseng contains 14 anti-AML active components and 64 related target genes. Through PPI analysis, it was found that among all target genes, CXCL8, STAT1, F3, TNFAIP3, and PLAU had the highest centrality. KEGG pathway analysis showed that the AGE-RAGE and NF-kappa B receptor signaling pathways might play a key role in coordinating chemoresistance treatment in AML. Molecular docking results demonstrated that the main active ingredients of immunomodulatory herbs have a strong binding affinity with hub genes.

Conclusion:In summary, this study has successfully identified the active components, potential targets, and pathways of ginseng in treating AML chemoresistance. It offers new insights into the molecular mechanisms through which ginseng aids in the treatment of AML and lays a foundation for future research in this field. Moreover, these potential active ingredients serve as a reliable source for AML drug screening.

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2025
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