Hederagenin alleviates neuroinflammation response by regulating glutamate-induced ferroptosis in HT22 cells
10.3969/j.issn.1009-0126.2024.10.022
- VernacularTitle:常春藤皂苷元通过抑制谷氨酸诱导的铁死亡缓解HT22细胞的炎性反应
- Author:
Yuxin FENG
1
;
Heran WANG
;
Yazhuo HU
;
Hongmei SUN
;
Xiaoxue ZHANG
;
Xiuling MIAO
;
Zihan LI
;
Jianjun JIA
Author Information
1. 100853 北京,解放军医学院
- Keywords:
Alzheimer disease;
glutamic acid;
inflammation;
hederagenin
- From:
Chinese Journal of Geriatric Heart Brain and Vessel Diseases
2024;26(10):1221-1225
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the regulatory role of hederagenin(HG)on glutamate(Glu)-in-duced ferroptosis and corresponding inflammatory responses in mouse hippocampal neuron HT22 cells and investigate its potential mechanisms.Methods HT22 cells were randomly divided into control,Glu and HG groups(n=3).The cells of the control group received no treatment,the cells of the Glu group were treated with 35 mmol/L Glu for 24 h to establish a cellular model of ferroptosis in Alzheimer's disease,and the cells of the HG group were treated with 0.5 μmol/L HG and 35 mmol/L Glu for 24 h simultaneously.FerroOrange fluorescent probe was used to de-tect intracellular Fe2+.The production of reactive oxygen species(ROS),mitochondrial membrane potential,and levels of inflammatory factors TNF-α,IL-1β and IL-6 in the cells were assessed.Finally,the expression of the key regulator of iron death,glutathione peroxidase 4(GPX4)was measured.Results Compared to the control group,the levels of intracellular Fe2+,ROS,TNF-α,IL-1β,and IL-6 were significantly elevated,while the mitochondrial membrane potential was obvi-ously reduced in the Glu group(P＜0.05,P＜0.01).The HG group had significantly decreased Fe2+,ROS,TNF-α,IL-1β,and IL-6 and enhanced mitochondrial membrane potential than the Glu group(P＜0.05,P＜0.01).The GPX4 expression was significantly lower in the Glu group than the control group(1.00±0.02 vs 0.46±0.04,P＜0.01),and was notably higher in the 0.5 and 1.0 μmol/L HG groups when compared to the Glu group(0.64±0.03 and 0.59±0.05 vs 0.46±0.04,P＜0.01).Conclusion HG inhibits ferroptosis by regulating GPX4 expression,and thereby effec-tively alleviates the inflammatory response.
