Effects of Shen-Huang granule on Aβ25-35-induced ferroptosis of HT22 cells via Nrf2/HO-1/GPX4 pathway
10.3969/j.issn.1000-4718.2025.04.014
- VernacularTitle:基于Nrf2/HO-1/GPX4通路探讨参黄冲剂对Aβ25-35诱导的HT22细胞铁死亡的影响
- Author:
Xiaohan WANG
1
;
Mengyu LIU
;
Yahan ZHANG
;
Ruijie XU
;
Yuetong ZHAO
;
Xu HAN
Author Information
1. 南京中医药大学,江苏 南京 210023
- Publication Type:Journal Article
- Keywords:
Shen-Huang granule;
Alzheimer disease;
ferroptosis;
Nrf2/HO-1/GPX4 signaling pathway;
HT22 cells
- From:
Chinese Journal of Pathophysiology
2025;41(4):743-749
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To investigate the effect and mechanism of Shen-Huang granule(SHG)on Aβ25-35-induced ferroptosis in HT22 cells.METHODS:An in vitro model of Alzheimer disease(AD)was established by treating HT22 cells with Aβ25-35.The cells were divided into the following groups:control group,model group(Aβ25-35 group),ferroptosis inhibitor ferrostatin-1(Fer-1)group,low-dose SHG(SHG-L)group,and high-dose SHG(SHG-H)group.Cell viability was assessed using the Cell Counting Kit-8(CCK-8)assay.Ultrastructural changes in each group were observed via trans-mission electron microscopy.The intracellular levels of reactive oxygen species(ROS)were measured by flow cytometry.Iron deposition and lipid peroxidation levels were evaluated by examining Fe2+,total superoxide dismutase(SOD),and malondialdehyde(MDA)levels.Western blot analysis was employed to detect the protein expression of cyclooxygenase 2(TfR1),ferritin heavy chain 1(FTH1),nuclear factor E2-related factor 2(Nrf2),and heme oxygenase-1(HO-1).RE-SULTS:Compared to the control group,the model group exhibited mitochondrial shrinkage,increased membrane densi-ty,and decreased cristae.Levels of ROS,Fe2+,and MDA were significantly elevated,while SOD levels were markedly re-duced.The protein expression of SLC7A11,GPX4,FTH1,Nrf2,and HO-1 was significantly down-regulated,whereas the expression of COX2 and TfR1 was significantly up-regulated.In comparison to the model group,the morphology and structure of mitochondria improved in the Fer-1,low-dose SHG,and high-dose SHG groups.ROS,Fe2+,and MDA levels decreased while SOD levels increased.Furthermore,the expression of SLC7A11,GPX4,FTH1,Nrf2,and HO-1 was sig-nificantly up-regulated,while COX2 and TfR1 expression was significantly down-regulated.CONCLUSION:Shen-Huang granule can inhibit Aβ25-35-induced ferroptosis in HT22 cells,and the underlying mechanism may involve the Nrf2/HO-1/GPX4 signaling pathway.
