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Volume 27
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10.3390/ijms27073140
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Grapefruit By-Products as a Sustainable Source of Bioaccessible Polyphenols with In Vitro Neuroprotective Potential

by
Laura Soriano-Romaní
1,
Elisa Gallego
1,
Marc Segarra-Mondéjar
1,
Noelia Teruel
2,
Alejandra Hernández-Bueno
2,
Alessandro Colletti
3 and
María Celeste Ruiz-Aracil
2,*
1
AINIA, C/Benjamín Franklin 5-11, 46980 Valencia, Spain
2
Marensotrumtech S.L., C/del Comercio 5, 03380 Alicante, Spain
3
Department of Science and Drug Technology, University of Turin, 10125 Turin, Italy
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2026, 27(7), 3140; https://doi.org/10.3390/ijms27073140
Submission received: 10 March 2026 / Revised: 23 March 2026 / Accepted: 27 March 2026 / Published: 30 March 2026
(This article belongs to the Special Issue Bioactive Compounds in Neurodegenerative Diseases)
Versions Notes

Abstract

Cognitive decline and neurodegenerative disorders represent a growing global health challenge, while effective preventive strategies remain limited. Citrus by-products, particularly grapefruit residues, constitute a rich and underexploited source of polyphenols, including flavonoids with reported antioxidant and neuroprotective properties. In this study, grapefruit-derived stabilized extract (GDSE) was evaluated using an in vitro neuronal model combined with dynamic simulated gastrointestinal digestion to assess the bioaccessibility and retained biological activity of key polyphenolic compounds. The soluble intestinal fraction of the digested formulation significantly reduced oxidative stress in dopaminergic-differentiated SH-SY5Y cells and was associated with changes in the expression of genes associated with neurotrophic support, dopaminergic signalling, and neuronal survival. In parallel, simulated digestion preserved a substantial proportion of major flavonoids, such as naringin and narirutin. Consequently, GDSE retained a moderate level of bioaccessible polyphenols and flavonoids, supporting the maintenance of its biological activity after digestion. Overall, these findings indicate that the formulation retains measurable bioactivity after simulated gastrointestinal digestion and modulates molecular markers associated with neuronal survival in vitro. While further in vivo and clinical studies are needed to fully establish its relevance for neuroprotection, the findings provide evidence that grapefruit-derived polyphenolic preparations could represent a potential source of bioactive compounds for further investigation as nutraceutical ingredients.
Keywords: citrus paradisi; agro-industrial residues; antioxidant activity; oxidative stress; simulated digestion; neuronal cells citrus paradisi; agro-industrial residues; antioxidant activity; oxidative stress; simulated digestion; neuronal cells

Share and Cite

MDPI and ACS Style

Soriano-Romaní, L.; Gallego, E.; Segarra-Mondéjar, M.; Teruel, N.; Hernández-Bueno, A.; Colletti, A.; Ruiz-Aracil, M.C. Grapefruit By-Products as a Sustainable Source of Bioaccessible Polyphenols with In Vitro Neuroprotective Potential. Int. J. Mol. Sci. 2026, 27, 3140. https://doi.org/10.3390/ijms27073140

AMA Style

Soriano-Romaní L, Gallego E, Segarra-Mondéjar M, Teruel N, Hernández-Bueno A, Colletti A, Ruiz-Aracil MC. Grapefruit By-Products as a Sustainable Source of Bioaccessible Polyphenols with In Vitro Neuroprotective Potential. International Journal of Molecular Sciences. 2026; 27(7):3140. https://doi.org/10.3390/ijms27073140

Chicago/Turabian Style

Soriano-Romaní, Laura, Elisa Gallego, Marc Segarra-Mondéjar, Noelia Teruel, Alejandra Hernández-Bueno, Alessandro Colletti, and María Celeste Ruiz-Aracil. 2026. "Grapefruit By-Products as a Sustainable Source of Bioaccessible Polyphenols with In Vitro Neuroprotective Potential" International Journal of Molecular Sciences 27, no. 7: 3140. https://doi.org/10.3390/ijms27073140

APA Style

Soriano-Romaní, L., Gallego, E., Segarra-Mondéjar, M., Teruel, N., Hernández-Bueno, A., Colletti, A., & Ruiz-Aracil, M. C. (2026). Grapefruit By-Products as a Sustainable Source of Bioaccessible Polyphenols with In Vitro Neuroprotective Potential. International Journal of Molecular Sciences, 27(7), 3140. https://doi.org/10.3390/ijms27073140

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