Identification of Antileukemic Compound From Ginger by Integrating UHPLC–MS, Network Pharmacology, Molecular Docking, Molecular Dynamics Simulation, and In Vitro and In Vivo Experimental Validation

Abstract

ABSTRACT Acute myeloid leukemia (AML) is a prevalent pediatric hematologic malignancy associated with a poor clinical prognosis, largely due to drug‐induced toxicity, the emergence of resistance, and frequent disease relapse. Edible plants offer promising complementary therapeutic approaches through their bioactive compounds, which are characterized by favorable safety profiles. Zingiber officinale (ginger), commonly consumed both as a dietary component and as a traditional medicinal herb, has garnered increasing scientific interest; however, its potential antileukemic properties remain largely unexplored. Crude extracts from four ginger cultivars exhibited antileukemic activity in AML cells. Metabolomic profiling was used to screen for candidate constituents, and Arctigenin was selected for further investigation. Its presence in the ginger extracts was verified by targeted UHPLC–MS analysis using an authentic standard, followed by evaluation of its antileukemic activity. Arctigenin showed potent and selective cytotoxicity against AML cells, particularly HL60 cells. Network pharmacology was employed to predict potential molecular targets, followed by molecular docking and 100‐ns molecular dynamics simulations to evaluate potential interactions, suggesting PARP1 and NFκB1 as potential molecular targets. Experimental analyses further demonstrated that Arctigenin induced apoptosis and altered NFκB and PARP protein expression in AML cells. In vivo experiments demonstrated that Arctigenin significantly suppressed tumor growth in an AML xenograft mouse model, achieving efficacy comparable to that of cytarabine, without inducing hepatosplenic toxicity or metabolic disturbances. These findings provide the first evidence supporting ginger as a novel phytochemical resource for AML therapy and support Arctigenin as a promising antileukemic candidate, underscoring its potential for incorporation into food‐based or plant‐derived therapeutic strategies.