The investigation of protective effects of isosteviol sodium on cerebral ischemia by metabolomics approach using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry

Biomed Chromatogr. 2018 Dec;32(12):e4350. doi: 10.1002/bmc.4350. Epub 2018 Aug 22.

Abstract

Cerebral ischemia remains a major cause of mortality and a long-term disability with limited therapies. Isosteviol sodium (STV-Na) was proved to exert significant protective effects on cerebral ischemia, but the protective mechanism was not understood. In this study, the protective effects of STV-Na on cerebral ischemia were investigated by the metabolomics approach based on ultra-high performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry technique. The models of ischemic rats were established and the brain tissues were employed for metabolomics analyses. The principal component analysis showed that the model group was clearly separated from the sham group, while both STV-Na and edaravone groups were located between the sham and the model groups, which indicated that STV-Na as well as edaravone had protective effects on cerebral ischemia. Eighteen differential metabolites which had significant differences between the sham and the model groups were screened and identified. After the administration of STV-Na, all 18 differential metabolites were regulated to the levels between the sham and the model groups, and 12 of them presented significant differences between the model and STV-Na groups. The pathway analysis indicated that the protective effects of STV-Na on cerebral ischemia might be associated with the regulation of several metabolic pathways, i.e. glycerophospholipid metabolism, arachidonic acid metabolism and linoleic acid metabolism.

Keywords: UPLC-Q-TOF/MS; cerebral ischemia; isosteviol sodium; metabolomics.

MeSH terms

  • Animals
  • Brain Ischemia / metabolism*
  • Chromatography, High Pressure Liquid / methods
  • Diterpenes, Kaurane / chemistry
  • Diterpenes, Kaurane / pharmacology*
  • Linoleic Acid / metabolism
  • Male
  • Metabolome / drug effects*
  • Metabolomics / methods*
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Reproducibility of Results
  • Tandem Mass Spectrometry / methods

Substances

  • Diterpenes, Kaurane
  • Neuroprotective Agents
  • isosteviol
  • Linoleic Acid