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Panpan Chen, Zihan Zhu, Haoyuan Geng, Xiaoqing Cui, Yuhao Han, Lei Wang, Yaqi Zhang, Heng Lu, Xiao Wang, Yun Zhang, Chenglong Sun. Integrated Spatial Metabolomics and Transcriptomics Decipher the Hepatoprotection Mechanisms of Wedelolactone and Demethylwedelolactone on Non-alcoholic Fatty Liver Disease[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2023.11.017
Citation: Panpan Chen, Zihan Zhu, Haoyuan Geng, Xiaoqing Cui, Yuhao Han, Lei Wang, Yaqi Zhang, Heng Lu, Xiao Wang, Yun Zhang, Chenglong Sun. Integrated Spatial Metabolomics and Transcriptomics Decipher the Hepatoprotection Mechanisms of Wedelolactone and Demethylwedelolactone on Non-alcoholic Fatty Liver Disease[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2023.11.017

Integrated Spatial Metabolomics and Transcriptomics Decipher the Hepatoprotection Mechanisms of Wedelolactone and Demethylwedelolactone on Non-alcoholic Fatty Liver Disease

doi: 10.1016/j.jpha.2023.11.017
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This study was supported by the National Natural Science Foundation of China (Grant No.: 82273888), Natural Science Foundation of Shandong Province (Grant No.: ZR2022QH257, ZR2020YQ60), Shandong Major Technological Innovation Project (2021CXGC010508), Taishan Scholars Program of Shandong Province (Program Nos.: tsqn202103096, tsqn202211204), and Shandong Province Science and Technology Small and Medium Enterprises Innovation Ability Enhancement Project (Project No.: 2022TSGC2210).

  • Received Date: Jul. 27, 2023
  • Accepted Date: Nov. 27, 2023
  • Rev Recd Date: Nov. 12, 2023
  • Available Online: Nov. 30, 2023
  • 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 Eclipta 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.
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