Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, School of Pharmacy, Southwest Medical University, Luzhou 646000, China.
School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
Biomolecules. 2024 Sep 11;14(9):1147. doi: 10.3390/biom14091147.
Stimulating erythropoiesis is essential in the treatment of various types of anemia. Sheng Xue Ning (SXN) is commonly used in China as an iron supplement to treat iron deficiency anemia, renal anemia, and anemia in pregnancy. This research reports a novel effect of SXN in enhancing the proliferation of hematopoietic stem/progenitor cell (HSPC) to promote erythropoiesis in the bone marrow, which is distinct from conventional iron supplements that primarily aid in the maturation of red blood cells. Employing a model of hematopoietic dysfunction induced by X-ray exposure, we evaluated the efficacy of SXN in restoring hematopoietic function. SXN significantly promoted the recovery of peripheral erythroid cells and enhanced the proliferation and differentiation of Lin/c-KIT/Sca-1 HSPC in mice exposed to X-ray irradiation. Our results showed that SXN elevated the expression of stem cell factor (SCF) and activated the SCF/c-KIT/PI3K/AKT signaling pathway, facilitating the proliferation and differentiation of HSPC. In vitro, SXN markedly enhanced the proliferation of bone marrow nucleated cell (BMNC) and the colony-forming capacity of BFU-E, CFU-E, and CFU-GM, while also elevating the expression of proteins involved in the SCF/c-KIT/PI3K/AKT pathway in BMNC. Additionally, SXN enhanced the proliferation and differentiation of mesenchymal stem cell (MSC) and increased SCF secretion. In conclusion, SXN demonstrates the capacity to enhance erythropoiesis by upregulating SCF expression, thereby promoting HSPC proliferation and differentiation via the SCF/c-KIT/PI3K/AKT pathway. SXN may offer a new strategy for improving the activity of HSPC and promoting erythropoiesis in the treatment of hematopoiesis disorders.
刺激红细胞生成对于治疗各种类型的贫血至关重要。生血宁在中国通常被用作铁补充剂，用于治疗缺铁性贫血、肾性贫血和妊娠贫血。本研究报道了生血宁促进骨髓造血干细胞/祖细胞（HSPC）增殖以促进红细胞生成的新作用，这与传统的铁补充剂不同，后者主要有助于红细胞的成熟。我们采用 X 射线照射诱导的造血功能障碍模型，评估了生血宁恢复造血功能的疗效。生血宁显著促进了外周红细胞的恢复，并增强了 X 射线照射小鼠 Lin/c-KIT/Sca-1 HSPC 的增殖和分化。我们的结果表明，生血宁上调了干细胞因子（SCF）的表达，并激活了 SCF/c-KIT/PI3K/AKT 信号通路，促进了 HSPC 的增殖和分化。在体外，生血宁显著增强了骨髓有核细胞（BMNC）的增殖和 BFU-E、CFU-E 和 CFU-GM 的集落形成能力，同时还上调了 BMNC 中参与 SCF/c-KIT/PI3K/AKT 通路的蛋白表达。此外，生血宁增强了间充质干细胞（MSC）的增殖和分化，并增加了 SCF 的分泌。总之，生血宁通过上调 SCF 的表达来增强红细胞生成，从而通过 SCF/c-KIT/PI3K/AKT 通路促进 HSPC 的增殖和分化。生血宁可能为改善 HSPC 的活性和促进造血障碍治疗中的红细胞生成提供一种新策略。
