Wogonin induces ferroptosis of rat CIA-FLS cells via NRF2/HO-1 sig-naling pathway
10.3969/j.issn.1000-4718.2024.07.016
- VernacularTitle:汉黄芩素通过NRF2/HO-1信号途径诱导大鼠CIA-FLS细胞铁死亡
- Author:
Lingfei HE
1
;
Chaofan ZHANG
;
Jie LIAN
;
Aoxuan SHEN
;
Qiannan DONG
;
Xiao KANG
;
Hao WU
Author Information
1. 湖北恩施学院,湖北 恩施 455099
- Keywords:
wogonin;
rheumatoid arthritis;
CIA-FLS cells;
NRF2/HO-1 signaling pathway;
ferroptosis
- From:
Chinese Journal of Pathophysiology
2024;40(7):1276-1282
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To investigate the mechanism by which wogonin(WOG)induces ferroptosis in collagen-in-duced arthritis rat fibroblast-like synoviocytes(rat CIA-FLS cells)through the nuclear factor E2-related factor 2(NRF2)/heme oxygenase-1(HO-1)signaling pathway.METHODS:Rat CIA-FLS cells were divided into:control group,low,medium,and high dose of(25,50 and 100 μmol/L)WOG group,ferroptosis inhibitor(LIP-1)group,LIP-1+high dose WOG group,HO-1 agonist cobalt protoporphyrin(COPP)group,and COPP+high dose WOG group.CCK-8 assay was used for cell viability.Crystal violet staining was used for for cell morphology.The levels of oxidative stress markers gluta-thione(GSH),malondialdehyde(MDA),and superoxide dismutase(SOD)were measured.DCFH-DA fluorescent probe was used to detect the intracellular reactive oxygen species(ROS)content as well as Western blot to detect the protein ex-pression levels of Kelch-like ECH-associated protein 1(KEAP-1),NRF2 and HO-1.RESULTS:Compared with the nor-mal control group,administration of WOG treatment resulted in a significant decrease in CIA-FLS cell viability(P<0.01),a significant increase in the level of oxidative stress(P<0.01),a significant increase in the content of ROS(P<0.01),a significant decrease in the level of expression of NRF2 and HO-1 proteins(P<0.01),and a significant increase in the level of KEAP-1(P<0.01)in the rat.Compared with the WOG group,the LIP-1-treated group showed a significant increase in cell viability(P<0.01),a significant decrease in the level of oxidative stress(P<0.01),and a significant de-crease in the content of ROS(P<0.01).Compared with the WOG group,the addition of COPP resulted in a significant in-crease in the protein expression levels of NRF2 and HO-1(P<0.01)and a significant decrease in KEAP-1 levels(P<0.01).CONCLUSION:WOG can induce ferroptosis in rat CIA-FLS cells by promoting oxidative stress through the NRF2/HO-1 signaling pathway.
