Serum metabolomics-based study on the mechanism of action of bergapten in the treatment of liver fibrosis

WU Huixing; ZHANG Zhenhua; LONG Changrui; GUO Guifen; WANG Yanyu; CHEN Yanchun; FU Juxiong; XIANG Shijian; ZHOU Benjie; LU Chengyu

doi:10.6039/j.issn.1001-0408.2024.13.05

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Serum metabolomics-based study on the mechanism of action of bergapten in the treatment of liver fibrosis

更新时间：2024-07-10

- Serum metabolomics-based study on the mechanism of action of bergapten in the treatment of liver fibrosis
- ZHONGGUO YAOFANG Vol. 35, Issue 13, Pages: 1570-1575(2024)
- 作者机构：
  
  1.广东医科大学药学院，广东东莞　523808
  2.中山大学附属第七医院药学部，广东深圳　518107
  3.惠东县人民医院血液净化中心，广东惠州　513600
  4.深圳市中药活性物质筛选与转化重点实验室，广东深圳　518107
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2024.13.05
  CLC： R965
- Published：15 July 2024，
  
  Received：27 February 2024，
  
  Revised：03 June 2024，
- 稿件说明：
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吴辉星,张振华,龙昌锐等.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 ^Δ[J].中国药房,2024,35(13):1570-1575.

WU Huixing,ZHANG Zhenhua,LONG Changrui,et al.Serum metabolomics-based study on the mechanism of action of bergapten in the treatment of liver fibrosis[J].ZHONGGUO YAOFANG,2024,35(13):1570-1575.
吴辉星,张振华,龙昌锐等.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 ^Δ[J].中国药房,2024,35(13):1570-1575. DOI： 10.6039/j.issn.1001-0408.2024.13.05.

WU Huixing,ZHANG Zhenhua,LONG Changrui,et al.Serum metabolomics-based study on the mechanism of action of bergapten in the treatment of liver fibrosis[J].ZHONGGUO YAOFANG,2024,35(13):1570-1575. DOI： 10.6039/j.issn.1001-0408.2024.13.05.

摘要

目的

基于血清代谢组学技术研究佛手柑内酯（BP）治疗肝纤维化的作用及机制。

方法

将40只小鼠分为正常对照组（0.5%羧甲基纤维素钠溶液）、模型组（0.5%羧甲基纤维素钠溶液）

和BP低、高剂量组（50、100 mg/kg），每组10只。除正常对照组外其余3组小鼠均采用四氯化碳诱导肝纤维化模型。同时，各组小鼠灌胃相应药物/溶剂，每日1次，连续8周。末次给药后，检测小鼠血清中丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）水平，观察小鼠肝组织病理形态学变化，检测小鼠肝组织中

-平滑肌肌动蛋白（

-SMA）、Ⅰ型胶原蛋白（Collagen Ⅰ）表达，同时对小鼠血清进行代谢组学分析。

结果

与模型组比较，BP低、高剂量组小鼠血清中ALT、AST水平和肝组织中

-SMA、Collagen Ⅰ蛋白表达水平均显著降低（

＜0.05），肝组织的纤维化程度显著改善。代谢组学结果显示，BP高剂量组和模型组共有175个血清差异代谢物，其中18个物质上调、157个物质下调，涉及的主要代谢途径有嘧啶代谢、丁酸盐代谢、脂肪酸合成、酪氨酸代谢、

-丙氨酸代谢、烟酸和烟酰胺代谢以及谷胱甘肽代谢等。

结论

BP可能通过调节肝纤维化小鼠血清中嘧啶代谢、丁酸盐代谢和谷胱甘肽代谢等途径达到治疗肝纤维化的作用。

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

-smooth muscle actin （

-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

-SMA and Collagen Ⅰ in liver tissue were decreased significantly in BP high-dose and low-dose groups （

＜0.05）， while liver fibrosis was improved significantly. Meanwhile， metabo

lomics 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，

-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.

关键词

佛手柑内酯肝纤维化血清代谢组学差异代谢物代谢途径

Keywords

liver fibrosisserum metabolomicsdifferential metabolitesmetabolic pathway

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