Renshen Yangrongtang Alleviating Myelosuppression by Reducing Neutrophil Extracellular Traps Through Regulating ROS/MPO
10.13422/j.cnki.syfjx.20241722
- VernacularTitle:人参养荣汤通过调控ROS/MPO减少中性粒细胞胞外诱捕网缓解骨髓抑制
- Author:
Jing ZHANG
1
;
Rongxing LIU
2
;
Jinhao ZENG
3
;
Qing NIAN
1
Author Information
1. Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu 610072, China
2. The Second Affiliated Hospital, Army Medical University, Chongqing 400037, China
3. Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China
- Publication Type:Journal Article
- Keywords:
Renshen Yangrongtang;
myeloperoxidase (MPO);
reactive oxygen species (ROS);
neutrophil extracellular traps (NETs);
myelosuppression
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2025;31(6):39-46
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the potential mechanism of Renshen Yangrongtang in alleviating myelosuppression by regulating the expression of reactive oxygen species (ROS), myeloperoxidase (MPO), and neutrophil extracellular traps (NETs). MethodsK562 cells were divided into blank group, etoposide group (40 μmol·L-1), and etoposide+Renshen Yangrongtang freeze-dried powder groups with low-, medium-, and high-dose (2, 4, 8 g·L-1). Liquid chromatography-mass spectrometry (LC-MS) was used to determine the freeze-dried powder of Renshen Yangrongtang. Enzyme-Linked Immunosorbent Assay (ELISA) was used to detect ROS, MPO, and NETs expression in each group. Western blot analysis was performed to assess intracellular MPO and NE expressions. Twenty 8-week-old male mice were randomly divided into blank group, etoposide group (100 mg·kg-1), and etoposide + Renshen Yangrongtang groups with low-, medium-, and high-dose (0.1, 0.5, 2.0 g·kg-1). Except for the blank group that received PBS via gavage at room temperature, and the etoposide group that received an intraperitoneal injection for 3 days, the remaining groups received gavage of Renshen Yangrongtang for 14 consecutive days after 3 days of etoposide administration. The peripheral blood related indicators were detected through an automated hematology analyzer; Western blot analysis was performed to assess MPO and neutrophil elastase (NE) expression changes in the marrow cells of mice. Enzyme-linked immunosorbent assay (ELISA) was used to detect ROS, MPO, and NETs changes in the marrow cells of mice. MPO and NE on femur bones were stained through immunohistochemistry. Scanning electron microscopy was used to analyze the structural changes of NETs in the marrow cells of mice after drug administration. ResultsLC-MS results showed that the freeze-dried powder of Renshen Yangrongtang contained complete technical materials such as Chinese angelica, Astragalus mongholicus, and ginseng. In K562 cells, compared with the etoposide group, ELISA results indicated that the concentrations of MPO, ROS, and NETs in the etoposide + Renshen Yangrongtang medium and high-dose groups were decreased (P<0.05, P<0.01), and Western blot data showed that the etoposide high-dose group significantly reduced the expression of MPO and NE protein in K562 cells (P<0.05, P<0.01). In vivo, compared with the etoposide group, the number of RBC, WBC, and PLT in the etoposide+Renshen Yangrongtang high-dose group increased significantly (P<0.05). ELISA results suggested that in the etoposide+Renshen Yangrongtang low-, medium-, and high-dose groups, the concentration of mice ROS, MPO, and NETs significantly decreased (P<0.05, P<0.01). Western blot results revealed that compared with the etoposide group, the expressions of MPO and NE in the marrow cells of mice in the etoposide + Renshen Yangrongtang low-, medium- and high-dose groups were significantly decreased (P<0.05, P<0.01). Scanning electron microscopy observations revealed that Renshen Yangrongtang reduced the NETs structure generation in the marrow cells of mice after the influence of etoposide. ConclusionRenshen Yangrongtang can alleviate etoposide-induced myelosuppression by inhibiting ROS/MPO and reducing the formation of intracellular NETs.