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Sanguisorba parviflora (Maxim) Takeda alleviates cyclophosphamide‐induced leukopenia via regulating the hematopoietic cell‑specific protein 1‑associated protein X‑1 gene
Author(s) -
Meng Lingkai,
Li Jie,
Meng Xiangli,
Zhou Yang,
Wang Jingxin,
Liu Shijuan,
Zhao Yujia
Publication year - 2021
Publication title -
journal of clinical pharmacy and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.622
H-Index - 73
eISSN - 1365-2710
pISSN - 0269-4727
DOI - 10.1111/jcpt.13450
Subject(s) - leukopenia , reactive oxygen species , apoptosis , biology , flow cytometry , microbiology and biotechnology , western blot , biochemistry , gene , chemotherapy , genetics
What is known and the objective Our previous studies have shown that saponins of Sanguisorba parviflora (Maxim) Takeda ( Sp . T ) relieved cyclophosphamide‐induced myelosuppression in mice with leukopenia. The hematopoietic cell‐specific protein 1‑associated protein X‑1 ( HAX‑1 ) participated in the survival of neutrophils through the regulation of mitochondrial function. This study aimed to comprehensively identify the role of HAX ‐ 1 in Sp . T to alleviate leukopenia. Methods HAX ‐ 1 expression was examined in the peripheral blood neutrophils using real‐time polymerase chain reaction (PCR), Western blot analysis and immunohistochemical staining. Neutrophil apoptosis was measured by flow cytometry. Mitochondrial function was evaluated via reactive oxygen species (ROS) generation and mitochondrial membrane potential ( ΔΨm ) integrity. Results and Discussion Our study indicated that the expression of the HAX‑1 gene was significantly decreased in the peripheral blood neutrophils of leukopenia patients compared with healthy donors. The saponins of Sp . T induced HAX ‐ 1 expression and promoted myeloid progenitor cell (mEB8‐ER cell) viability, while overexpression of HAX‑1 reduced the production of reactive oxygen species (ROS) and maintained the integrity of the mitochondrial membrane potential. Cyclophosphamide‐induced mitochondrial dysfunction and apoptosis could be abrogated by treatment with Sp . T or the addition of metformin. What is new and our Conclusion Our data support a mechanism where Sp . T protects against chemotherapy‐induced leukopenia by regulating HAX ‐ 1 gene expression in a mitochondrial‐dependent manner.