With the increasing incidence of cancer, chemotherapy, radiotherapy, and surgery have been widely used for cancer treatment (Horeweg et al., 2022, Rizzo et al., 2022). Among all cancer treatments, chemotherapy is a potential treatment option for the patients (Pomeroy et al., 2022, Lewicki et al., 2022). However, as chemotherapy has become more intensive, common complications of anticancer chemotherapy, including bone marrow damage, cardiotoxicity, and congestive cardiomyopathy, have attracted much attention (Kapalatiya et al., 2022, Conforti et al., 2022, Rizzo et al., 2020). Therefore, delaying or rejuvenating the adverse effects of chemotherapy is of great significance (Dutta et al., 2021).

Studies have revealed that chemotherapy induces bone marrow toxicity or myelosuppression, including bone growth arrest, low bone mass, osteonecrosis, and cellular senescence in the bone (Sakemura et al., 2022, Oh et al., 2022). Bone marrow-derived mesenchymal stem cells (BMSCs) are present in bone marrow and associated with age-related bone loss. It is well understood that the proliferative and differentiation potential of BMSCs include their proliferation ability, osteogenic differentiation potential, and senescence-associated gene expression (Corbeau et al., 2021, You et al., 2022a). Chemotherapy may alter the differentiation potential therefore causing cell senescence associated with dysregulation. It has been shown that BMSCs senescence is closely associated with osteoblast differentiation, bone marrow microenvironment (Zhang et al., 2021, Letarouilly et al., 2022).

Astragalus polysaccharides (APS), one of the main components of Astragalus membranaceus (Fisch.), has been reported to have immune enhancement, antitumor, antiinflammatory, antivirus and improve neurological functions (Sheik et al., 2021, Li et al., 2020, Meng et al., 2020, Guo et al., 2012). Studies have shown that APS has the ability to protect tumor-bearing mice from Taxol-induced cytotoxicity while protecting mice from cyclophosphamide-induced bone marrow suppression (Tang et al., 2021, Bao et al., 2021). In cyclophosphamide (Cy)-induced cells suppression, APS enhances recovery by regulating cell number, morphology, apoptosis and cell cycle of Cy-suppressed cells (Guo et al., 2012, Li et al., 2022).

Currently available researches have demonstrated that a number of signaling pathways such as bone morphogenetic protein (BMP) and mitogen-activated protein kinase (MAPK) signaling pathways are involved in the regulation and differentiation of BMSCs (Yu et al., 2021, Feng et al., 2018, El-Derany et al., 2021). Wnt/β-catenin signaling regulates cell renewal, repair, and inflammation (Schunk et al., 2021). Moreover, APS can protect bovine mammary epithelial cells from inflammation, stress, and oxidative injury via Wnt signaling. Studies have also revealed that APS can enhance the immune system in cancer patients by regulating the Wnt/β-catenin signaling pathways (Jiang and Mao, 2019, Fan et al., 2022).

In recent studies, APS has been reported to enhance the recovery of cyclophosphamide (Cy)-induced bone marrow and blood cell injury by increasing FOS expression (Bao et al., 2021, Zhang et al., 2019). However, the effects of APS on chemotherapy-induced senescence in BMSCs are yet to be elucidated. Based on the aforementioned literature, this study explored the effects of APS on Cy-induced mouse models and BMSCs. We speculated that APS protected BMSCs from apoptosis and senescence. In addition, we examined the effects of APS on BMSC differentiation and prefoliation, as well as the modulation of the Wnt/β-catenin signaling pathway. Therefore, in the present study, we established Cy-induced mouse and BMSCs cell models to verify the therapeutic effects of APS. We aimed to provide a scientific reference for the effects of APS on promoting osteogenic differentiation and senescence while exploring the exact mechanisms in Cy-suppressed BMSCs.