Therapeutic Potential of Adina rubella Hance Stem and Picroside III as a Differentiation Inducer in AML Cells via Mitochondrial ROS Accumulation

Acute myeloid leukemia (AML) is characterized by the accumulation of immature myeloid cells and a differentiation block, highlighting the urgent need for novel differentiation-inducing therapies. This study evaluated <i>Adina rubella</i> Hance (ARH) stem as a potent differentiation inducer by systematically screening 200 plant extracts. ARH stem promoted phenotypic differentiation in AML cells. In addition to its differentiation-inducing effects, ARH stem exhibited strong antileukemic activities, such as inhibiting cell proliferation, inducing cell death, and enhancing mitochondrial reactive oxygen species (mtROS) levels, the latter of which is critical for its differentiation-promoting activity. Comparative analysis with the extracts from other parts of the plant confirmed the superior efficacy of the stem extract because of its unique chemical composition. Ultra-high-performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry analysis identified Picroside III as a major active compound within the stem extract, capable of recapitulating ARH stem-induced differentiation and demonstrating significant antileukemic properties. These findings underscore the therapeutic potential of ARH stem and its active component, Picroside III, as promising agents for differentiation-based treatment strategies in AML.