Screening potential antileukemia agents from duckweed: Integration of chemical profiling, network pharmacology, and experimental validation.

Introduction: The identification of active dietary flavonoids in food is promising for novel drug discovery. The active ingredients of duckweed (a widely recognized food and herb with abundant flavonoids) that are associated with acute myeloid leukemia (AML) have yet to be identified, and their underlying mechanisms have not been elucidated.

Objectives: The objective of this study was to identify novel constituents exhibiting antileukemia activity in duckweed through the integration of chemical profiling, network pharmacology, and experimental validation.

Methods: First, high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was used to characterize the primary constituents of duckweed. Subsequently, AML cell-xenograft tumor models were used to validate the anticancer effect of duckweed extract. Furthermore, network pharmacology analysis was conducted to predict the potential active compounds and drug targets against AML. Lastly, based on these findings, two monomers (apiin and luteoloside) were selected for experimental validation.

Results: A total of 17 compounds, all of which are apigenin and luteolin derivatives, were identified in duckweed. The duckweed extract significantly inhibited AML cell growth in vivo. Furthermore, a total of 88 targets for duckweed against AML were predicted, with key targets including PTGS2, MYC, MDM2, VEGFA, CTNNB1, CASP3, EGFR, TP53, HSP90AA1, CCND1, MMP9, TNF, and MAPK1. GO and KEGG pathway enrichment analyses indicated that these targets were primarily involved in the apoptotic signaling pathway. Lastly, both apiin and luteoloside effectively induced apoptosis through CASP3 activation, and this effect could be partially reversed by a caspase inhibitor (Z-VAD).

Conclusion: Duckweed extract has an antileukemic effect, and apiin derived from duckweed shows potential as a treatment for AML.