白头翁皂苷B4通过保护骨髓造血微环境减轻环磷酰胺诱导的骨髓抑制
Anemoside B4 mitigates cyclophosphamide-induced myelosuppression via preserving the bone marrow microenvironment
摘要
Abstract
Background:Cyclophosphamide(CTX)induces myelosuppression,a dose-limiting adverse effect,through di-rect cytotoxicity to hematopoietic cells and disruption of the stromal microenvironment.Anemoside B4(AB4),a saponin derived from Pulsatilla chinensis,exhibits antioxidant,anti-apoptotic,anti-inflammatory,and im-munomodulatory activities;however,its role in protecting bone marrow from CTX-induced injury remains un-known. Objective:To investigate the potential of AB4 to mitigate CTX-induced myelosuppression and its underlying mechanisms using C57BL/6J mice. Methods:A CTX-induced myelosuppression model was established,with 40 mice randomly assigned to 5 groups(n=8 per group):Control,CTX alone,low-dose AB4(AB4-L),high-dose AB4(AB4-H),and granulocyte colony-stimulating factor(G-CSF,positive control).After 7 days of treatment,the following parameters were assessed:peripheral blood cell counts,spleen and thymus indices,bone marrow histology,levels of cytokines(granulocyte-macrophage colony-stimulating factor(GM-CSF),G-CSF,interleukin-6(IL-6),interleukin-1 beta(IL-1β)).Flow cytometric analysis(bone marrow mesenchymal stem cells(BMSCs)),reactive oxygen species(ROS),cell cycle,apoptosis),molecular assays(superoxide dismutase(SOD),malondialdehyde(MDA)),terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL),and western blotting for γ-H2AX,p53,etc.)were also performed. Results:Both doses of AB4 significantly increased red blood cell(RBC)and white blood cell(WBC)counts and elevated the thymus index(P＜0.05).AB4 normalized hemosiderin deposition and megakaryocyte numbers,reduced the spleen index(P＜0.01),increased levels of hematopoietic cytokines and BMSCs(P＜0.01),decreased ROS and MDA levels,restored SOD activity,downregulated the expression of y-H2AX,p53,BAX,and cleaved caspase-3/9(P＜0.01),and alleviated cell cycle arrest and apoptosis(P＜0.01). Conclusion:AB4 mitigates CTX-induced myelosuppression by preserving the bone marrow microenvironment,reducing oxidative stress and DNA damage,relieving cell cycle arrest,and suppressing apoptosis.These findings suggest AB4 holds promise for alleviating chemotherapy-related hematotoxicity.关键词
环磷酰胺/骨髓抑制/造血微环境/骨髓间充质干细胞/细胞周期/细胞凋亡Key words
Cyclophosphamide/Myelosuppression/Haematopoietic microenvironment/Bone marrow mesenchymal stem cells/Cell cycle/Apoptosis引用本文复制引用
刘璟钰,高红伟,王琴琴,倪兴华,苏倩,宁玉洁,谢晓芸,何金莹,杨世林,苑仁祎坤..白头翁皂苷B4通过保护骨髓造血微环境减轻环磷酰胺诱导的骨髓抑制[J].临床传统医学和药理学（英文）,2025,6(3):82-94,13.基金项目
This work was supported by Bagui Youth Outstanding Talent Culti-vation Project(2024 & 2025) （2024 & 2025）
and Project of Guangxi Young Qihuang Scholar[Grant number GXQH202408] （）
and Guangxi Natural Science Foundation Project[Grant number 2024JJA140449] （）
and Young Tal-ent Research Funding Project （）
and Young Elite Scientists Sponsorship Program by GXAST[Grant number 2025YESSGX031] （）
and the Doctoral Foundation of Guangxi University of Chinese Medicine[Grant num-ber 2022BS008] （）
and GL Special project of youth science and technol-ogy innovation ability improvement plan[Grant number YXY0000305] （）
and Guangxi University of Chinese Medicine Outstanding Youth Fund Project[Grant number 2023JQ002] （）
and Young Scientists Fund of the National Natural Science Foundation of China[Grant number NSFC,82404938,China]. （）
