Integrated spatial metabolomics and transcriptomics decipher the hepatoprotection mechanisms of wedelolactone and demethylwedelolactone on non-alcoholic fatty liver diseaseOA
Integrated spatial metabolomics and transcriptomics decipher the hepatoprotection mechanisms of wedelolactone and demethylwedelolactone on non-alcoholic fatty liver disease
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.
Panpan Chen;Yun Zhang;Chenglong Sun;Zihan Zhu;Haoyuan Geng;Xiaoqing Cui;Yuhao Han;Lei Wang;Yaqi Zhang;Heng Lu;Xiao Wang
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,ChinaBiology Institute,Qilu University of Technology(Shandong Academy of Sciences),Jinan,250103,ChinaKey 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,250355,ChinaKey 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
Spatial metabolomicsTranscriptomicsNon-alcoholic fatty liver diseaseWedelolactoneDemethylwedelolactone
《药物分析学报（英文）》 2024 (004)
552-561 / 10
This study was supported by the National Natural Science Foundation of China(Grant No.:82273888),Natural Science Foundation of Shandong Province(Grant Nos.ZR2022QH257,and ZR2020YQ60),Shandong Major Technological Innovation Project(Project No.:2021CXGC010508),Taishan Scholars Program of Shandong Province(Program Nos.:tsqn202103096,and tsqn202211204),and Shandong Province Science and Technology Small and Medium Enterprises Innovation Ability Enhancement Project(Project No.:2022TSGC2210).
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