Jin Zongxin, Mollica Fabio, Huang Yeqin, Guernelli Susanna, Baschieri Andrea, Diquigiovanni Chiara, Rizzardi Nicola, Valenti Francesca, Pincigher Luca, Bergamini Christian, Amorati Riccardo
Department of Chemistry, "G. Ciamician" University of Bologna, Via Gobetti 83, 40129, Bologna, Italy.
Institute for Organic Synthesis and Photoreactivity, (ISOF) National Research Council of Italy (CNR), Via Gobetti 101, 40129, Bologna, Italy.
Chemistry. 2024 Dec 23;30(72):e202403320. doi: 10.1002/chem.202403320. Epub 2024 Nov 10.
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.
