Artemisia annua L. (A. annua) has long been documented in traditional Chinese medicine for managing hemorrhagic conditions, attributed to its cooling and hemostatic properties. These historical applications suggest a potential role of A. annua in platelet-related disorders, although its hematopoietic mechanisms remain unclear. To investigate the thrombopoietic activity of A. annua, identify its bioactive constituent, and elucidate the molecular mechanisms underlying its effects on thrombopoiesis. Chemical profiling identified major compounds in A. annua. MK differentiation was assessed in K562, Meg-01 cells, and primary murine haematopoietic stem and progenitor cells (HSPCs). A murine radiation-induced thrombocytopenia (RIT) model was used to evaluate in vivo efficacy. Molecular docking, drug affinity responsive target stability (DARTS), and signaling assays were conducted to explore molecular mechanisms. A. annua promoted MK differentiation, upregulating CD41/CD42b and enhancing polyploidization. Artemisinin was identified as the principal active compound. It promoted MK maturation in vitro and restored platelet counts, MK numbers, and HSPC populations in RIT mice without inducing systemic toxicity. Artemisinin also reduced bone marrow (BM) apoptosis and DNA damage while restoring platelet function. Mechanistically, artemisinin directly bound to FLT3 and activated the FLT3/MAPK pathway, leading to increased phosphorylation of MEK/ERK and upregulation of NF-E2 and TAL1. FLT3 and ERK inhibition abrogated these effects. Artemisinin is a potent thrombopoietic agent that acts via direct activation of FLT3 and its downstream MAPK signaling cascade. The findings identify FLT3 as a novel therapeutic target for thrombocytopenia and support the potential clinical application of artemisinin in radiation-related hematological disorders.

Breast cancer, a predominant global health issue, requires ongoing exploration of new therapeutic strategies. Palbociclib (PAL), a well-known cyclin-dependent kinase (CDK) inhibitor, plays a critical role in breast cancer treatment. While its efficacy is recognized, the interplay between PAL and cellular autophagy, particularly in the context of the RAF/MEK/ERK signaling pathway, remains insufficiently explored. This study investigates PAL’s inhibitory effects on breast cancer using both in vitro (MCF7 and MDA-MB-468 cells) and in vivo (tumor-bearing nude mice) models. Aimed at elucidating the impact of PAL on autophagic processes and exploring the potential of combining it with trametinib (TRA), an MEK inhibitor, our research seeks to address the challenge of PAL-induced drug resistance. Our findings reveal that PAL significantly decreases the viability of MCF7 and MDA-MB-468 cells and reduces tumor size in mice while showing minimal cytotoxicity in MCF10A cells. However, PAL also induces protective autophagy, potentially leading to drug resistance via the RAF/MEK/ERK pathway activation. Introducing TRA effectively neutralized this autophagy, enhancing PAL’s anti-tumor efficacy. A combination of PAL and TRA synergistically reduced cell viability and proliferation, and in vivo studies showed notable tumor size reduction. In conclusion, the PAL and TRA combination emerges as a promising strategy for overcoming PAL-induced resistance, offering a new horizon in breast cancer treatment.