Danggui Shaoyaosan Regulates Nrf2/SLC7A11/GPX4 Signaling Pathway to Inhibit Ferroptosis in Rat Model of Non-alcoholic Fatty Liver Disease
10.13422/j.cnki.syfjx.20242442
- VernacularTitle:当归芍药散调节Nrf2/SLC7A11/GPX4信号通路干预非酒精性脂肪性肝病大鼠铁死亡的机制
- Author:
Xinqiao CHU
1
;
Yaning BIAO
2
;
Ying GU
2
;
Meng LI
1
;
Tiantong JIANG
1
;
Yuan DING
1
;
Xiaping TAO
1
;
Shaoli WANG
1
;
Ziheng WEI
3
;
Zhen LIU
1
;
Yixin ZHANG
2
Author Information
1. Guang'anmen Hospital of China Academy of Chinese Medical Sciences， Beijing 100053， China
2. College of Pharmacy， Hebei University of Chinese Medicine， Shijiazhuang 050200， China
3. The First Affiliated Hospital of Hebei University of Chinese Medicine， Shijiazhuang 050011， China
- Publication Type:Journal Article
- Keywords:
Danggui Shaoyaosan;
non-alcoholic fatty liver disease;
ferroptosis;
nuclear factor E2-related factor 2 （Nrf2）/solute carrier family 7 member 11 （SLC7A11）/glutathione peroxidase 4 （GPX4） signaling pathway
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2025;31(16):35-42
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the effect of Danggui Shaoyaosan on ferroptosis in the rat model of non-alcoholic fatty liver disease （NAFLD） and explore the underlying mechanism based on the nuclear factor E2-related factor 2 （Nrf2）/solute carrier family 7 member 11 （SLC7A11）/glutathione peroxidase 4 （GPX4） signaling pathway. MethodsThe sixty SD rats were randomly grouped as follows： control， model， Yishanfu （0.144 g·kg-1）， and low-， medium-， and high-dose （2.44， 4.88， and 9.76 g·kg-1， respectively） Danggui Shaoyaosan. A high-fat diet was used to establish the rat model of NAFLD. After 12 weeks of modeling， rats were treated with corresponding agents for 4 weeks. Then， the body weight and liver weight were measured， and the liver index was calculated. At the same time， serum and liver samples were collected. The levels or activities of total cholesterol （TC）， triglycerides （TG）， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， and Fe2+ in the serum and TC， TG， free fatty acids （FFA）， malondialdehyde （MDA）， superoxide dismutase （SOD）， glutathione peroxidase （GPX）， and Fe2+ in the liver were measured. Hematoxylin-eosin staining and oil red O staining were employed to observe the pathological changes in the liver. Immunofluorescence was used to assess the reactive oxygen species （ROS） content in the liver. Mitochondrial morphology was observed by transmission electron microscopy. The protein levels of Nrf2， SLC7A11， GPX4， transferrin receptor 1 （TFR1）， and divalent metal transporter 1 （DMT1） in the liver were determined by Western blot. ResultsCompared with the control group， the model group showed increases in the body weight， liver weight， liver index， levels or activities of TC， TG， ALT， AST， and Fe2+ in the serum， levels of TC， TG， FFA， MDA， Fe2+， and ROS in the liver， and protein levels of TFR1 and DMT1 in the liver （P<0.01）， and decreases in the activities of SOD， GPX and the protein levels of Nrf2， SLC7A11， and GPX4 in the liver （P<0.05， P<0.01）. Meanwhile， the liver tissue in the model group presented steatosis， iron deposition， mitochondrial shrinkage， and blurred or swollen mitochondrial cristae. Compared with the model group， all doses of Danggui Shaoyaosan reduced the body weight， liver weight， liver index， levels or activities of TC， TG， ALT， AST， and Fe2+ in the serum， levels of TC， TG， FFA， MDA， Fe2+， and ROS in the liver， and protein levels of TFR1 and DMT1 in the liver （P<0.01）， while increasing the activities of SOD and GPX and the protein levels of Nrf2， SLC7A11， and GPX4 in the liver （P<0.01）. Furthermore， Danggui Shaoyaosan alleviated steatosis， iron deposition， and mitochondrial damage in the liver. ConclusionDanggui Shaoyaosan may inhibit lipid peroxidation and ferroptosis by activating the Nrf2/SLC7A11/GPX4 signaling pathway to treat NAFLD.
