Osthole protects APAP-induced liver injury in mice by inhibiting the TGF-β1/Smad pathway through upregulation of Tif1γ
10.12092/j.issn.1009-2501.2025.07.003
- VernacularTitle:蛇床子素通过上调Tif1γ抑制TGF-β1/Smad通路保护APAP诱导的小鼠肝损伤
- Author:
Yiran HE
1
;
Yang HE
;
Guoyan DENG
;
Zhiqiang FAN
;
Zizhao TANG
;
Feng WEI
;
Linqi OUYANG
Author Information
1. 湖南中医药大学第一附属医院,长沙 410007,湖南
- Publication Type:Journal Article
- Keywords:
osthole;
Tif1γ;
TGF-β1/Smad;
liver in-jury;
hepatic stellate cell
- From:
Chinese Journal of Clinical Pharmacology and Therapeutics
2025;30(7):889-898
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To investigate the protective ef-fect of osthole(Ost)on APAP-induced liver injury in mice and its molecular mechanism.METHODS:We established the APAP-induced liver injury model in mice,and Ost was used to intervene.The expres-sion of AST,ALT,SOD,ROS,MDA,LDH,GSH-PX in mice plasma were detected by biochemical meth-od.HE staining was used to observe the changes of liver tissue structure.Immunofluorescence assay was used to detect the expression of Tif1γ and Smad4 in liver tissue.The mRNA expression of IL-1β,IL-6,TNF-α,Smad4,and Tif1γ were detected by qRT-PCR.Western blot was applied to assess the protein expression of Smad2/3 and pSmad2/3 in liver tissue.RESULTS:Compared with the control group,the liver structure destruction and hepato-cyte death was increased,ALT,AST,ROS,MDA and LDH were increased,while SOD and GSH-PX were decreased,and the mRNA expressions of IL-1β,IL-6 and TNF-α were increased in the model group.Compared with the model group,the Ost interven-tion group had improved liver structure and de-creased liver cell death;decreased ALT,AST,ROS,MDA and LDH,increased SOD and GSH-PX,and de-creased expression of IL-1β,IL-6 and TNF-α mRNA.Compared with the control group,liver tissues of model mice showed increased expression of pS-mad2/3,Smad4 protein and Smad4 mRNA,and de-creased Tif1γ protein and mRNA.Compared with the model group,the liver tissues of the Ost inter-vention group showed decreased expression of pS-mad2/3,Smad4 protein and Smad4 mRNA,and in-creased expression of Tif1γ protein and mRNA.CONCLUSION:Ost can improve liver function,re-duce oxidative stress and inflammatory reaction,and protect hepatocyte damage induced by APAP in mice,which may be related to the up-regulation of Tif1γ and inhibition of TGF-β1/Smad signaling pathway.
