Pro‐aromatic Natural Terpenes as Unusual “Slingshot” Antioxidants with Promising Ferroptosis Inhibition Activity
Ferroptosis is a cell death mechanism based on extensive cellular membrane peroxidation, implicated in neurodegenerative and other diseases. The essential oil component γ-terpinene, a natural monoterpene with a unique highly oxidizable pro-aromatic 1,4-cyclohexadiene skeleton, inhibits peroxidation of polyunsaturated lipid in model heterogeneous systems (micelles and liposomes). Upon H-atom abstraction, an unstable γ-terpinene-derived peroxyl radical is formed, that aromatizes to p-cymene generating HOO⋅ radicals. As HOO⋅ are small and hydrophilic radicals, they quickly diffuse outside the lipid core, blocking the radical chain propagation of polyunsaturated lipids. This unprecedented antioxidant "slingshot" mechanism explains why γ-terpinene shows a protective activity against ferroptosis, being effective at submicromolar concentrations in human neuroblastoma (SH-SY5Y) cells.
Authors
- Fabio Mollica (ORCID: https://orcid.org/0000-0002-5169-2807)
- Riccardo Amorati (ORCID: https://orcid.org/0000-0002-6417-9957)
- Susanna Guernelli
- Francesca Valenti (ORCID: https://orcid.org/0000-0003-1695-4979)
- Nicola Rizzardi (ORCID: https://orcid.org/0000-0002-9294-7116)
- Chiara Diquigiovanni (ORCID: https://orcid.org/0000-0003-3124-6946)
- Andrea Baschieri (ORCID: https://orcid.org/0000-0002-2108-8190)
- Luca Pincigher (ORCID: https://orcid.org/0009-0002-9806-2789)
- Zongxin Jin (ORCID: https://orcid.org/0009-0009-5619-9980)
- Christian Bergamini (ORCID: https://orcid.org/0000-0003-4387-5117)
- Yeqin Huang (ORCID: https://orcid.org/0000-0003-2468-8674)
Institutions
- National Academies of Sciences, Engineering, and Medicine (US)
- Institute of Organic Synthesis and Photoreactivity (IT)
- National Research Council (IT)
- University of Bologna (IT)
Publication Details
- Journal
- Chemistry - A European Journal
- Published
- 2024-10-11
- DOI
- https://doi.org/10.1002/chem.202403320
- Citations
- 5
- Primary Topic
- Metabolomics and Mass Spectrometry Studies
- Type
- article
- Field-Weighted Citation Impact
- 1.17
Funders
- European Commission
- Eni
- Chinese Service Center for Scholarly Exchange