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

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

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  • 国家科技期刊平台
  • NETL
  • NSTL
  • 万方数据
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.

Spatial metabolomicsTranscriptomicsNon-alcoholic fatty liver diseaseWedelolactoneDemethylwedelolactone

Panpan Chen、Zihan Zhu、Haoyuan Geng、Xiaoqing Cui、Yuhao Han、Lei Wang、Yaqi Zhang、Heng Lu、Xiao Wang、Yun Zhang、Chenglong Sun

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Key Laboratory for Natural Active Pharmaceutical Constituents Research in Universities of Shandong Province,School of Pharmaceutical Sciences,Qilu University of Technology(Shandong Academy of Sciences),Jinan,250014,China

Key Laboratory for Applied Technology of Sophisticated Analytical Instruments of Shandong Province,Shandong Analysis and Test Center,Qilu University of Technology(Shandong Academy of Sciences),Jinan,250014,China

School of Pharmacy,Shandong University of Traditional Chinese Medicine,Jinan,25

Biology Institute,Qilu University of Technology(Shandong Academy of Sciences),Jinan,250103,China

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National Natural Science Foundation of ChinaNatural Science Foundation of Shandong ProvinceNatural Science Foundation of Shandong ProvinceShandong Major Technological Innovation ProjectTaishan Scholars Program of Shandong ProvinceTaishan Scholars Program of Shandong ProvinceShandong Province Science and Technology Small and Medium Enterprises Innovation Ability Enhancement Project

82273888ZR2022QH257ZR2020YQ60Project :2021CXGC010508Program :tsqn202103096tsqn2022112042022TSGC2210

2024

10.1016/j.jpha.2023.11.017

药物分析学报(英文)
西安交通大学

药物分析学报(英文)

影响因子：0.244
ISSN：2095-1779
年,卷(期)：2024.14(4)
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