Serum metabolomics-based study on the mechanism of action of bergapten in the treatment of liver fibrosis
- VernacularTitle:基于血清代谢组学研究佛手柑内酯治疗肝纤维化的作用机制
- Author:
Huixing WU
1
;
Zhenhua ZHANG
2
;
Changrui LONG
1
;
Guifen GUO
3
;
Yanyu WANG
2
;
Yanchun CHEN
2
;
Juxiong FU
1
;
Shijian XIANG
2
,
4
;
Benjie ZHOU
2
,
4
;
Chengyu LU
1
Author Information
1. School of Pharmacy，Guangdong Medical University，Guangdong Dongguan 523808，China
2. Dept. of Pharmacy，the Seventh Affiliated Hospital of Sun Yat-sen University，Guangdong Shenzhen 518107，China
3. Blood Purification Center of Huidong County People’s Hospital，Guangdong Huizhou 513600，China
4. Shenzhen Key Laboratory of Chinese Medicine Active Substance Screening and Translational Research，Guangdong Shenzhen 518107，China
- Publication Type:Journal Article
- Keywords:
bergapten;
liver fibrosis;
serum metabolomics;
differential metabolites;
metabolic pathway
- From:
China Pharmacy
2024;35(13):1570-1575
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To study the effects of bergapten in the treatment of liver fibrosis and its mechanism based on serum metabolomics. METHODS Forty mice were divided into normal control group （0.5% carboxymethyl cellulose sodium solution）， model group （0.5% carboxymethyl cellulose sodium solution）， and BP low-dose and high-dose groups （50， 100 mg/kg）， with 10 mice in each group. Except for the normal control group， the other three groups were all treated with carbon tetrachloride to induce liver fibrosis model； they were given relevant medicine/solution intragastrically， once a day， for consecutive 8 weeks. After the last medication， the levels of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） in serum were detected， and liver pathological changes were observed； the expressions of α-smooth muscle actin （α-SMA） and Collagen Ⅰ were detected in liver tissue； the serum of the mice was collected for metabolomics analysis. RESULTS Compared with the model group， serum levels of ALT and AST and protein expressions of α-SMA and Collagen Ⅰ in liver tissue were decreased significantly in BP high-dose and low-dose groups （P＜0.05）， while liver fibrosis was improved significantly. Meanwhile， metabolomics analyses showed that there were a total of 175 serum differential metabolites in the BP high-dose group and model group， of which 18 substances were upregulated and 157 substances were downregulated； the main metabolic pathways involved in bergapten intervention were pyrimidine metabolism， butanoate metabolism， fatty acid synthesis， tyrosine metabolism， β-alanine metabolism， nicotinic acid and nicotinamide metabolism， glutathione metabolism， etc. CONCLUSIONS BP is effective in the treatment of liver fibrosis by regulating pyrimidine metabolism， butanoate metabolism， glutathione metabolism and so on in rats with liver fibrosis.
