Study on the metabolism of natural sesquiterpene lactones in human liver microsomes using LC-Q-TOF-MS/MS

Abstract

Sesquiterpene lactones are naturally occurring, highly active ­specialised metabolites, which are biosynthesized by important medicinal plants, fulfilling many functions. The in vitro metabolism of parthenolide (1), grosheimin (2), carbetolide C (3), 8α-O-(3,4-dihydroxy-­methylenebutanoyloxy)-dehydromelitensin (4) and arteludovicinolide A (5) was examined using human liver microsomes. Phase I, phase II (glucuronidation), as well as combined phase I + II metabolism were studied. Metabolites were identified via liquid chromatography-high resolution quadrupole time-of-flight mass spectrometry. Monohydroxylated, hydrated, carboxylated, methylated derivatives, together with corresponding monoglucuronides were detected, suggesting that the metabolism of sesquiterpene lactones is changeable due to structural features and scaffold diversity, though the lactone ring is the main site of metabolism.

Graphical Abstract

Keywords:

• Sesquiterpene lactones
• asteraceae
• parthenolide
• grosheimin
• human liver microsomes
• metabolism
• LC-MS

Acknowledgments

The authors wish to Mr. Josef Kiermaier and Mr. Wolfgang Söllner for recording the MS data (Zentrale Analytik, Faculty of Chemistry and Pharmacy, University of Regensburg).

Data availability statement

Derived data supporting the findings of this study are available from MEG on request.

Disclosure statement

The authors report there are no competing interests to declare.

Additional information

Funding

Part of this work was supported by European Social Fund-ESF (MIS-5000432), implemented by the State Scholarships Foundation (ΙKY) for MEG and the Hellenic Foundation for Research and Innovation (HFRI) under the HFRI PhD Fellowship grant (Fellowship Number: 16274) for CB.