Qingdainone, a novel bioactive compound in Realgar‒Indigo naturalis, induced apoptosis and differentiation in ATRA‐sensitive and ‐resistant acute promyelocytic leukaemia cells

Acute promyelocytic leukaemia (APL) is a subtype of acute myeloid leukaemia with high mortality rates. The Realgar‒Indigo naturalis formula (RIF), a traditional Chinese medicine, shows promise in APL treatment, but its mechanisms remain unclear. The active compounds in RIF were identified using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and SwissTarget databases. Intersection targets between APL‐related genes and RIF targets were analysed using the STRING database and Cytoscape. Molecular docking was performed using CB‐Dock to evaluate the binding affinity of Qingdainone to key targets. Cell viability, apoptosis and differentiation were assessed in NB4 and NB4‐R1 cells treated with Qingdainone by cell counting kit‐8 assay and flow cytometry. Network pharmacology identified Qingdainone as a key bioactive compound in RIF. Molecular docking showed strong binding affinities of Qingdainone to targets such as CCND1, CDK1, CDK4, CASP3 and CASP7. In vitro experiments demonstrated that Qingdainone inhibited proliferation, induced G0/G1‐phase arrest, and promoted apoptosis in both all‐trans retinoic acid (ATRA)‐sensitive and ‐resistant APL cells. Furthermore, Qingdainone induced differentiation in NB4 and NB4‐R1 cells, as evidenced by increased expression of CD11b, CD11c and CD14. Qingdainone from RIF shows potent anti‐leukaemic effects by inhibiting proliferation, inducing apoptosis and promoting differentiation in APL cells. The present study highlighted Qingdainone as a potential therapeutic agent, especially for ATRA‐resistant cases, and offered insights into mechanisms of RIF in APL treatment.