Back to Search Start Over

Integrated spatial metabolomics and transcriptomics decipher the hepatoprotection mechanisms of wedelolactone and demethylwedelolactone on non-alcoholic fatty liver disease

Authors :
Panpan Chen
Zihan Zhu
Haoyuan Geng
Xiaoqing Cui
Yuhao Han
Lei Wang
Yaqi Zhang
Heng Lu
Xiao Wang
Yun Zhang
Chenglong Sun
Source :
Journal of Pharmaceutical Analysis, Vol 14, Iss 4, Pp 100910- (2024)
Publication Year :
2024
Publisher :
Elsevier, 2024.

Abstract

Eclipta prostrata L. has been used in traditional medicine and known for its liver-protective properties for centuries. Wedelolactone (WEL) and demethylwedelolactone (DWEL) are the major coumarins found in E. prostrata L. However, the comprehensive characterization of these two compounds on non-alcoholic fatty liver disease (NAFLD) still remains to be explored. Utilizing a well-established zebrafish model of thioacetamide (TAA)-induced liver injury, the present study sought to investigate the impacts and mechanisms of WEL and DWEL on NAFLD through integrative spatial metabolomics with liver-specific transcriptomics analysis. Our results showed that WEL and DWEL significantly improved liver function and reduced the accumulation of fat in the liver. The biodistributions and metabolism of these two compounds in whole-body zebrafish were successfully mapped, and the discriminatory endogenous metabolites reversely regulated by WEL and DWEL treatments were also characterized. Based on spatial metabolomics and transcriptomics, we identified that steroid biosynthesis and fatty acid metabolism are mainly involved in the hepatoprotective effects of WEL instead of DWEL. Our study unveils the distinct mechanism of WEL and DWEL in ameliorating NAFLD, and presents a “multi-omics” platform of spatial metabolomics and liver-specific transcriptomics to develop highly effective compounds for further improved therapy.

Details

Language :
English
ISSN :
20951779
Volume :
14
Issue :
4
Database :
Directory of Open Access Journals
Journal :
Journal of Pharmaceutical Analysis
Publication Type :
Academic Journal
Accession number :
edsdoj.9128eb55b81648878ea259ff8cda6d89
Document Type :
article
Full Text :
https://doi.org/10.1016/j.jpha.2023.11.017