Effects of Yinchenhao Decoction Plus Zexie Decoction on Ferroptosis Mediated by IRE1 Signaling Pathway of Endoplasmic Reticulum Stress in NASH Mice
- VernacularTitle:茵陈蒿汤合泽泻汤对NASH小鼠内质网应激IRE1信号通路介导铁死亡的影响
- Author:
Xiaoyu SHA
1
;
Yanyang HUANG
;
Baoying LIU
;
Siqi YANG
;
Lianqun JIA
;
Guoyuan SUI
Author Information
- Publication Type:Journal Article
- Keywords: Non-alcoholic steatohepatitis; Yinchenhao Decoction plus Zexie Decoction; Endoplasmic reticulum stress; IRE1; Ferroptosis
- From: World Science and Technology-Modernization of Traditional Chinese Medicine 2025;27(6):1699-1708
- CountryChina
- Language:Chinese
- Abstract: Objective To explore the effect of Yinchenhao Decoction plus Zexie Decoction on ferroptosis mediated by IRE1 signaling pathway of endoplasmic reticulum stress in NASH mice.Methods Fifty C57BL/6J mice were randomly divided into blank control group,model group,Yinchenhao decoction group,Zexia decoction group and Hefang group,with 10 mice in each group.Except the blank control group,the other groups were fed with high-fat diet.After 20 weeks,Yinchenhao Tang group,Zexia Tang group and Hefang group were respectively given the corresponding drug by intragastric administration,once a day for 8 weeks.HE staining,oil red O staining and Masson staining were used to observe the pathological changes of liver tissue,automatic biochemical analyzer was used to detect blood lipid and liver function indexes,and RT-qPCR was used to detect the mRNA levels of TFR1,FPN,XBP1,Xbp1s and XBP1-dependent UPR target genes.The expressions of GRP78,P-IRE1α,GPX4,TFR1 and FPN proteins in liver were detected by Western Blot,the contents of Fe2+and MDA were detected by colorimetry,SOD activity was detected by WST-8,ROS content was detected by ELISA,and TG content in mouse liver tissue was detected by GPO-PAP.Results Compared with the model group,the NAS scores of Yinchenhao Tang group,Zexia Tang group and Hefang group were significantly reduced,and the effect of Hefang group was more significant.Compared with the blank control group,the liver lipid deposition of model mice was obvious,and the liver lipid deposition of Yinchenhao Tang group,Zexia group and Hefang group were improved to varying degrees,and the effect of Hefang group was more significant.Masson staining results showed that compared with blank control group,liver fibrosis was obvious in model group,Yinchenhao Decoction group,Zexia group and Hefang group,the degree of liver fibrosis was improved,and the effect of Hefang group was more significant.Compared with the blank control group,the levels of serum TC,HDL-C,LDL-C,AST and ALT in the model group were significantly increased,the contents of TG,Fe2+,MDA and ROS in the liver were significantly increased,and the activity of SOD was significantly decreased.The mRNA expression levels of Xbp1,Xbp1s,Dnajb9,Edem1,Sec61a1,Bip,Chop and TFR1were significantly up-regulated,the mrna expression levels of FPN were significantly down-regulated,and the protein expression levels of GRP78,P-IREα,GPX4 and TFR1 in liver were significantly increased.The expression level of FPN protein decreased significantly.Compared with model group,the serum levels of TG,TC,LDL-C,AST and ALT in the combined formula group were significantly decreased,the contents of TG,Fe2+,MDA and ROS in the liver of the combined formula group were significantly decreased,and the activity of SOD was significantly increased.The mRNA expression levels of Xbp1,Xbp1s,Dnajb9,Edem1,Sec61a1,Bip,Cho and TFR1 in liver were significantly decreased,the mrna expression level of FPN was significantly increased,and the protein expression levels of GRP78,P-IRE1α,GPX4 and TFR1 in liver were significantly down-regulated.The expression level of FPN protein was significantly up-regulated.Conclusion Yinchenhao Decoction plus Zexie Decoction may ameliorate NASH by inhibiting ferroptosis of hepatocytes through IRE1α pathway of endoplasmic reticulum stress.
