Study on the mechanism of hyperoside regulating hepatic lipid synthesis to ameliorate non-alcoholic fatty liver disease in mice
- VernacularTitle:金丝桃苷调控肝脏脂质合成改善小鼠非酒精性脂肪性肝病的机制研究
- Author:
Changrui LONG
1
,
2
;
Shijian XIANG
2
,
3
;
Zhenhua ZHANG
2
,
3
;
Huixing WU
2
,
3
;
Benjie ZHOU
2
,
3
;
Chengyu LU
1
Author Information
1. School of Pharmacy，Guangdong Medical University，Guangdong Dongguan 523808，China
2. Shenzhen Key Laboratory of Active Substances Screening and Transformation of Traditional Chinese Medicine，Guangdong Shenzhen 518107，China
3. Dept. of Pharmacy，the Seventh Affiliated Hospital of Sun Yat-sen University，Guangdong Shenzhen 518107，China
- Publication Type:Journal Article
- Keywords:
hyperoside;
non-alcoholic fatty liver disease;
lipid synthesis;
lipidomics;
PPARα
- From:
China Pharmacy
2025;36(6):668-673
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To investigate the improvement mechanism of hyperoside （HYP） on non-alcoholic fatty liver disease （NAFLD）. METHODS Male C57BL/6 mice were randomly divided into normal （NFD） group， model （HFD） group and HYP group， with 8 mice in each group. Except for NFD group， the mice in other groups were fed with HF60 high-fat diet to establish NAFLD model； HYP group was simultaneously given HYP 100 mg/kg intragastrically every day， for 16 consecutive weeks. The body weight and liver weight of mice in each group were recorded 16 h after the last medication； the histopathological changes and lipid accumulation in the liver were observed， and the contents of triglyceride （TAG） in liver tissue and serum contents of TAG， aspartate transaminase （AST） and alanine transaminase （ALT） were measured； LC-MS/MS method was adopted to detect lipid changes in the liver tissue of mice for lipidomics analysis， and protein expressions of lipid synthesis-associated proteins peroxisome proliferator-activated receptor α （PPARα） were also tested. Human hepatocellular carcinoma cell line HepG2 was divided into normal control group， model group， HYP low-concentration group （50 μmol/L）， HYP high-concentration group （100 μmol/L）， HYP low-concentration+GW6471 （PPARαinhibitor） group， and HYP high-concentration+GW6471 group. Except for normal control group， the remaining cells were induced with oleic acid and palmitic acid to establish a high-fat cell model. The accumulation of lipid droplets in each group of cells was observed， and the TAG content was detected. RESULTS Compared with HFD group， HYP group exhibited significant reductions in liver fat vacuoles， lipid accumulation， liver weight， and TAG content in liver tissue， as well as serum contents of ALT， AST and TAG （P＜0.05）. Additionally， the expression of PPARα protein in liver tissue was significantly increased （P＜0.05）， and the pathological morphological changes associated with NAFLD were alleviated. Lipidomic analysis revealed that HYP significantly reduced the levels of TAG， diacylglycerol and other lipids in the liver. Compared with model group， cellular lipid droplet accumulation and TAG content decreased significantly in HYP low- and high-concentration groups （P＜0.05）； GW6471 could significantly reverse the improvement effect of HYP on above indicators （P＜0.05）. CONCLUSIONS HYP can effectively ameliorate NAFLD induced by a high-fat diet in mice， and the mechanism may be related to the activation of PPARα to regulate hepatic lipid synthesis.
