B-lymphocytopenia among myelosuppression is the most intractable side effect of chemotherapy. Here, we investigated ways to alleviate 5-fluorouracil-caused stress hematopoietic impairment. We found that intraperitoneally injected ASP (Angelica sinensis polysaccharides) (100 mg/kg per day), one main active ingredient of Angelica sinensis, for consecutive 7 days, significantly recovered mouse bone marrow pro-B and pre-B cells, reversed the capacity of CFU-PreB colony forming, thus alleviating B cell reduction in the spleen and peripheral blood, as well as ameliorating immunoglobin from spleen and serum. The mechanism is related to the protective effects of ASP on IL-7 producing cells, including perivascular Leptin + and CXCL12 + mesenchymal stem and progenitor cells (MSPCs), thus promoting IL-7 production, and activating IL-7R-mediated STAT5, PI3K-AKT signaling, including survival signals and EBF1, PAX5 transcription factor expression. Additionally, ASP’s IL-7 promoting effect was demonstrated to be associated with maintaining osteogenesis/adipogenesis balance of MSPCs via the NRF2 antioxidant pathway. Collectively, our findings indicate that ASP reverse stress B-lymphocytopenia via improving Nrf2 signaling, promoting IL-7 production in MSPCs, and subsequently maintaining survival, proliferation, and differentiation of B cell progenitors, which may represent a promising therapeutic strategy.
Home>Angelica sinensis polysaccharides ameliorated 5-Fluorouracil-induced damage of early B cell progenitors by alleviating oxidative stress of IL-7 producing mesenchymal stem and progenitor cells
Angelica sinensis polysaccharides ameliorated 5-Fluorouracil-induced damage of early B cell progenitors by alleviating oxidative stress of IL-7 producing mesenchymal stem and progenitor cells
- Impact factors: 7.5
- Publication: BIOMEDICINE & PHARMACOTHERAPY
- Author:Hanxianzhi Xiao, Yaping Wang, Ziling Wang, Biyao Wang, Ling Hu, Jiying Hou, Kunhang Du, Nianci Sun, Lu Wang
- DOI citation-doi:10.1016/j.biopha.2023.115599
- Date:2023-09-30