Effect of Coptidis Rhizoma-Fermentum Rubrum on Non-Alcoholic Fatty Liver Disease in Mice Based on Nrf2/GPX4 Ferroptosis Axis
10.13422/j.cnki.syfjx.20241108
- VernacularTitle:基于Nrf2-GPX4铁死亡轴探讨黄连-红曲对小鼠非酒精性脂肪肝的影响
- Author:
Yang YANG
1
;
Xiaobo ZHANG
2
;
Yong ZHANG
2
;
Fuming LU
3
;
Yaqi LUO
1
;
Xiaoyi WU
1
Author Information
1. Institute of Traditional Chinese Medicine（TCM），Sichuan Academy of TCM Sciences （The Second Hospital of Sichuan Province of TCM），Chengdu 610031，China
2. School of Basic Medicine，Chengdu University of TCM，Chengdu 611137，China
3. Zigong Hospital of TCM，Zigong 643010，China
- Publication Type:Journal Article
- Keywords:
Coptidis Rhizoma-Fermentum Rubrum;
fatty liver;
mice;
ferroptosis;
nuclear factor erythroid-2-related factor 2 （Nrf2）-glutathione peroxidase 4 （GPX4） axis
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2024;30(20):30-36
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo observe the effects of Coptidis Rhizoma-Fermentum Rubrum on non-alcoholic fatty liver disease （NAFLD） in mice and explore its possible mechanisms. MethodSixty male SPF C57BL/6J mice were randomly divided into six groups： control group， model group， low-， medium-， and high-dose Coptidis Rhizoma-Fermentum Rubrum group （0.75， 1.5， 3 g·kg-1）， and metformin group （0.075 g·kg-1）， with 10 mice in each group. NAFLD mouse models were induced by high-fat diet feeding for 24 weeks. The low， medium， and high-dose Coptidis Rhizoma-Fermentum Rubrum groups were administered corresponding doses of Coptidis Rhizoma-Fermentum Rubrum by gavage， while the control and model groups received an equivalent amount of saline for four weeks. Serum total cholesterol （TC）， triglycerides （TG）， free fatty acids （FFA）， and liver function markers including alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were measured using an automatic biochemical analyzer. Hematoxylin-eosin （HE） and oil red O staining were used to detect liver lipid deposition， and Prussian blue staining was used to measure liver ferrous ion levels. Western blot was performed to detect the expression of key proteins in the nuclear factor erythroid-2-related factor 2 （Nrf2）-glutathione peroxidase 4 （GPX4） axis. ResultAfter 24 weeks of high-fat feeding， compared with the control group， the model group showed significant increases in body weight， liver weight and liver index， and serum lipid levels （P<0.01）， as well as substantial hepatic lipid deposition with marked steatosis. Compared with the model group， Coptidis Rhizoma-Fermentum Rubrum intervention reduced body weight （P<0.01）， liver weight and liver index （P<0.01）， and serum lipid levels （P<0.05， P<0.01）， improved liver function （P<0.01）， and decreased hepatic lipid deposition， with the low-dose Coptidis Rhizoma-Fermentum Rubrum group showing the best effect. Western blot results showed that compared with those in the control group， the expression levels of Nrf2， heme oxygenase-1 （HO-1）， kelch-like ECH-associated protein 1（Keap1）， and GPX4 proteins in the model group were decreased （P<0.05， P<0.01）. Compared with the model group， Coptidis Rhizoma-Fermentum Rubrum increased the expression levels of these proteins （P<0.05， P<0.01）. ConclusionCoptidis Rhizoma-Fermentum Rubrum can alleviate fatty liver in mice， improve liver function， and reduce hepatic lipid deposition， possibly by regulating the Nrf2/GPX4 ferroptosis axis.
