Effect and mechanism of eriodictyol on non-alcoholic fatty liver disease by regulating MAPK and Nrf2/HO-1 signaling pathway
- VernacularTitle:圣草酚调控MAPK和Nrf2/HO-1信号通路缓解非酒精性脂肪肝的作用及机制
- Author:
Kaiyang WANG
1
;
Lie YUAN
2
,
3
;
Yi SONG
2
,
3
;
Qinglong LIU
4
;
Peiling ZHONG
2
,
3
;
Wenjun LI
4
;
Yongqing CAI
1
;
Xiaoli LI
2
,
3
;
Menghua ZENG
5
;
Jianhong CHEN
1
Author Information
1. Dept. of Pharmacy，Army Medical Center of PLA，Chongqing 400042，China
2. Dept. of Pharmacology，Chongqing Medical University，Chongqing 400016，China
3. Chongqing Key Laboratory of Drug Metabolism Research，Chongqing 400016，China
4. Dept. of Pharmacy，the Third Affiliated Hospital of Chongqing Medical University，Chongqing 401120，China
5. Dept. of Gastrointestinal Surgery，the First Affiliated Hospital of Chongqing Medical University，Chongqing 400016，China
- Publication Type:Journal Article
- Keywords:
eriodictyol;
non-alcoholic fatty liver disease;
mitogen-activated protein kinase;
factor-erythroid 2-related factor 2
- From:
China Pharmacy
2023;34(23):2880-2885
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To study the effect and potential mechanism of eriodictyol on non-alcoholic fatty liver disease （NAFLD）. METHODS Sixteen C57BL/6J mice were randomly divided into control group， NAFLD model group， and eriodictyol low-dose and high-dose groups （50， 100 mg/kg）， with 4 mice in each group. Except for control group， the other groups were fed with high fat diet to induce NAFLD model. After four weeks of preprocessing， they were given relevant medicine intraperitoneally （0.01 mL/g）， once a day， for 6 consecutive weeks. The body weight and liver weight of mice were measured， and the pathological damage of liver tissue in mice was observed. The levels of aspartate aminotransferase （AST）， alanine aminotransferase（ALT）， and triglycerides （TG） in serum， as well as the protein expressions of nuclear factor-erythroid 2-related factor 2 （Nrf2） and heme oxygenase-1 （HO-1） in liver tissue were determined. In vitro NAFLD model was established by using 0.5 mmol/L oleic acid （OA） in HepG2 cells. Normal control group， NAFLD model group and eriodictyol low-， medium- and high-concentration groups （50， 100， 150 μmol/L） were set up. HepG2 cells in drug groups were treated with eriodictyol for 24 h at the time of modeling. The lipid deposition was observed in cells， and the levels of TG， malondialdehyde （MDA） and reactive oxygen species （ROS） as well as the phosphorylation levels of the mitogen-activated protein kinase （MAPK） signal pathway related proteins [extracellular signal-regulated kinase （ERK）， c- Jun N-terminal kinase （JNK）] and the protein expressions of Nrf2 and HO-1 were all determined. RESULTS In the in vivo experiment， compared with the NAFLD model group， the body weight， liver weight， the serum levels of AST， ALT and TG were all decreased significantly in eriodictyol low- and high-dose groups （except for serum level of AST in eriodictyol low-dose group） （P＜0.01）； liver lipid deposition was reduced significantly and the protein expressions of Nrf2 and HO-1 in liver tissues were further up-regulated （P＜0.01）. In the in vitro experiment， compared with the NAFLD model group， the lipid deposition in hepatocytes was reduced in eriodictyol low-， medium- and high-concentration groups （P＜0.01）， and the levels of ROS， MDA and TG were down-regulated （P＜0.05 or P＜0.01）； the phosphorylation levels of ERK and JNK were significantly down-regulated （P＜0.01）， while the protein expressions of Nrf2 and HO-1 were up-regulated significantly （P＜0.01）. CONCLUSIONS Eriodictyol can inhibit MAPK signaling pathway and activate Nrf2/HO-1 signaling pathway to alleviate NAFLD.
