Supercritical CO₂-Derived Tomato Extract Activates Signaling Pathways to Reduce Oxidative Stress and Inflammation in Astrocyte Cells.

Authors

Serena Recalchi, Beatrice Mengoni, Barbara Scaglia, Marilena Esposito, Emiliano Montalesi, Valeria Manganelli, Gloria Riitano, Elena Fasciolo, Tuba Rana Caglar, Daniela Caissutti, Camilla Moliterni, Federica Armeli, Rita Businaro, Roberta Misasi, Maurizio Sorice, Antonella Capozzi

Published in

Nutrients. Volume 18. Issue 9. May 03, 2026. Epub May 03, 2026.

Abstract

In this study, we investigated the effect on antioxidant defenses of a tomato extract obtained by supercritical CO₂ extraction (sCO₂TE), evaluating whether this green extraction method preserves biological activity compared to a conventional tomato extract (CTE) and focusing on superoxide dismutase (SOD) and glutathione peroxidase (GPx) regulation, Nuclear factor erythroid 2-related factor 2 (NRF2) activation, reactive oxygen species (ROS) and lipid peroxidation modulation.
Human glioblastoma astrocytoma U-373 cells were pre-treated with sCO₂TE or conventional tomato extract (CTE) and subsequently exposed to sodium arsenite (AsNaO₂) to induce oxidative stress, or lipopolysaccharide (LPS) to trigger inflammatory signaling. Cell viability was assessed by Trypan Blue and MTT [3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide]; cell toxicity by propidium iodide staining. Intracellular ROS and lipid peroxidation were measured by flow cytometry. Gene expression of NRF2, SOD1 and GPX1 was analyzed by qRT-PCR, NRF2 activation and modulation of ERK1/2 (Extracellular Signal-Regulated Kinase 1/2) and NF-κB (Nuclear Factor kappa-light-chain-enhancer of activated B cells) were evaluated by Western blot.
Pre-treatment with sCO₂TE significantly reduced AsNaO₂-induced ROS production and lipid peroxidation, showing a stronger effect compared to CTE. sCO₂TE enhanced the expression of NRF2 phosphorylation and its downstream targets SOD1 and GPX1, particularly under oxidative stress conditions. In addition, sCO₂TE attenuated LPS-induced phosphorylation of ERK1/2 and NF-κB p65, suggesting anti-inflammatory activity.
These findings demonstrate that sCO₂TE preserves the antioxidant and anti-inflammatory properties of tomato-derived bioactives. The comparable efficacy of sCO₂TE and CTE supports the use of sCO₂ as a sustainable and solvent-free extraction method for the development of nutraceutical formulations targeting oxidative stress and neuroinflammation.

PMID:
42124065
Bibliographic data and abstract were imported from PubMed on 17 Sep 2026.

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