Praeruptorin A inhibits neutrophil inflammation through ferritin and its role in sepsis
10.3760/cma.j.cn112309-20240729-00282
- VernacularTitle:白花前胡甲素通过铁蛋白抑制中性粒细胞炎症反应及其在脓毒症中的作用
- Author:
Pengchao YU
1
;
Hong ZHENG
;
Yifan HU
;
Zhouxin YANG
;
Zejia YU
;
Jinnan XIA
;
Haiying HAN
;
Dongyang GUO
Author Information
1. 浙大城市学院医学院，杭州 310015
- Publication Type:Journal Article
- Keywords:
Sepsis;
Praeruptorin A;
Neutrophils;
Inflammatory cytokines;
Ferritin
- From:
Chinese Journal of Microbiology and Immunology
2025;45(3):248-255
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the potential of praeruptorin A (PA) in alleviating inflammatory damage in sepsis through the inhibition of ferritin expression.Methods:C57BL/6 mice were intraperitoneally injected with lipopolysaccharide (LPS) to establish the model of sepsis. After 6 and 12 h of PA intervention, serum levels of inflammatory cytokines IL-6 and TNF-α were measured by ELISA. Kidney tissues were collected at 72 h for HE staining to assess inflammatory cell infiltration and tissue damage. Human neutrophils were divided into four groups: control, LPS, ferritin, and LPS+ ferritin groups. After 12 h of intervention, qRT-PCR was used to detect the expression of IL-6 and TNF-α mRNA. In order to observe the effect of PA on the expression of inflammatory cytokines and ferritin, human neutrophils were grouped into control, LPS, and LPS+ PA (2/3/4 μmol/L) groups. After 12 h of intervention, qRT-PCR was performed to measure the expression of IL-1β, IL-6, TNF-α, and ferritin mRNA; ELISA was used to quantify the levels of IL-1β, IL-6, and TNF-α in culture supernatants; Western blot was used to analyze the expression of ferritin. Molecular docking was conducted to verify interactions between PA and ferritin.Results:Significant inflammatory cell recruitment, tissue damage, and elevated serum levels of IL-6 and TNF-α ( P<0.01) were observed in mice with LPS-induced sepsis. PA significantly inhibited cytokine secretion ( P<0.01) and alleviated tissue injury in sepsis mice. In human neutrophil models, ferritin upregulated the expression of IL-6 and TNF-α mRNA ( P<0.01); LPS stimulation alone increased the expression of IL-1β, IL-6, TNF-α, and ferritin at both mRNA and protein levels ( P<0.01), while co-stimulation with PA (3/4 μmol/L) significantly reversed the aforementioned results ( P<0.01). Molecular docking confirmed there were interaction sites between PA and ferritin. Conclusion:PA inhibits the release of inflammatory cytokines and alleviates tissue damage in sepsis, and the potential mechanism may involve modulating ferritin expression to suppress inflammatory responses.
