Pseudotargeted lipidomics analysis of scoparone on glycerophospholipid metabolism in non-alcoholic steatohepatitis mice by LC-MRM-MS

PeerJ. 2024 May 21:12:e17380. doi: 10.7717/peerj.17380. eCollection 2024.

Abstract

As the inflammatory subtype of nonalcoholic fatty liver disease (NAFLD), the progression of nonalcoholic steatohepatitis (NASH) is associated with disorders of glycerophospholipid metabolism. Scoparone is the major bioactive component in Artemisia capillaris which has been widely used to treat NASH in traditional Chinese medicine. However, the underlying mechanisms of scoparone against NASH are not yet fully understood, which hinders the development of effective therapeutic agents for NASH. Given the crucial role of glycerophospholipid metabolism in NASH progression, this study aimed to characterize the differential expression of glycerophospholipids that is responsible for scoparone's pharmacological effects and assess its efficacy against NASH. Liquid chromatography-multiple reaction monitoring-mass spectrometry (LC-MRM-MS) was performed to get the concentrations of glycerophospholipids, clarify mechanisms of disease, and highlight insights into drug discovery. Additionally, pathologic findings also presented consistent changes in high-fat diet-induced NASH model, and after scoparone treatment, both the levels of glycerophospholipids and histopathology were similar to normal levels, indicating a beneficial effect during the observation time. Altogether, these results refined the insights on the mechanisms of scoparone against NASH and suggested a route to relieve NASH with glycerophospholipid metabolism. In addition, the current work demonstrated that a pseudotargeted lipidomic platform provided a novel insight into the potential mechanism of scoparone action.

Keywords: Glycerophospholipid metabolism; NASH; Pseudotargeted lipidomics; Scoparone.

MeSH terms

  • Animals
  • Chromatography, Liquid / methods
  • Coumarins* / pharmacology
  • Coumarins* / therapeutic use
  • Diet, High-Fat / adverse effects
  • Disease Models, Animal
  • Glycerophospholipids* / metabolism
  • Lipid Metabolism / drug effects
  • Lipidomics* / methods
  • Male
  • Mass Spectrometry / methods
  • Mice
  • Mice, Inbred C57BL
  • Non-alcoholic Fatty Liver Disease* / drug therapy
  • Non-alcoholic Fatty Liver Disease* / metabolism
  • Non-alcoholic Fatty Liver Disease* / pathology

Substances

  • scoparone
  • Glycerophospholipids
  • Coumarins

Grants and funding

This work was supported by grants from the Natural Science Foundation of Hebei Province (No. H2019201426), the Science and Technology Project of Hebei Education Department (No. QN2021017), Medical Science Foundation of Hebei University (No. 2021A08), College Students’ Innovative Entrepreneurial Training Plan Program (No. 2022379). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.