Astragalus polysaccharides inhibit arsenic trioxide-induced BMSCs damage through inhibition of Jnk and p38 signaling pathways.

Objective: Arsenic trioxide (ATO) is a clinically effective anticancer agent used in the treatment of leukemia. However, it exerts adverse effects on non-tumor cells, including bone marrow mesenchymal stem cells (BMSCs). This study aims to investigate the protective role and molecular mechanism of traditional Chinese medicine Astragalus polysaccharides (APS) in mitigating ATO-induced apoptosis in BMSCs. Methods: BMSCs exposed to ATO (0.5 μmol/L) were treated with APS (20, 40, 100, and 200 μg/mL). Cell viability, proliferation, and migration were assessed by using MTT, EdU staining, Transwell, and scratch wound healing assays. Apoptosis was evaluated via TUNEL assay, Hoechst 33258 staining, and flow cytometry. Intracellular reactive oxygen species (ROS) and mitochondrial membrane potential were measured by using DCFH-DA and JC-1 staining. Apoptotic protein expression was analyzed by Western blotting. Results: ATO exposure significantly inhibited the proliferation and migration of BMSCs and induced apoptosis, while APS markedly attenuated the apoptosis of BMSCs induced by ATO, and significantly improved cell proliferation and migration (P < 0.01). Mechanistically, APS effectively reduced ATO-induced ROS (P < 0.01), while the protein expression of Bcl-2-associated X protein (Bax) and cleaved Caspase-3 was significantly decreased (P < 0.05), and the protein expression of Bcl-2 was significantly increased (P < 0.01). In addition, APS markedly decreased the protein expression of c-Jun N-terminal kinase (Jnk) and p38 in ATO-activated BMSCs (P < 0.05), and significantly decreased the protein expression of p16 and p53 (P < 0.01), and increased the protein expression of phosphorylated protein kinase B (p-Akt) and phosphorylated extracellular signal-regulated kinase (p-Erk) (P < 0.01, 0.05). Conclusion: Our study reveals that APS exert significant protective effects against ATO-induced apoptosis in BMSCs. The mechanisms involve suppressing ROS generation, maintaining mitochondrial membrane stability, enhancing cell viability, migration, and proliferation, as well as inhibiting Jnk and p38 mitogen-activated protein kinase (p38 MAPK) signaling pathways. The findings highlight potential molecular targets and novel strategies for the clinical prevention and treatment of ATO-related toxicity .