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Article

Capsaicin and Its Combination with Oleic Acid Affect Membrane Fatty Acid Remodeling and Cytokine–Chemokine Secretion in HepG2 Cells

1
Department of Oncology and Molecular Medicine, Istituto Superiore Di Sanità, Viale Regina Elena 299, 00161 Rome, Italy
2
Institute for Organic Synthesis and Photoreactivity (ISOF), National Research Council (CNR), Via P. Gobetti, 101, 40129 Bologna, Italy
3
Department of Chemistry, Dominican University, 7900 West Division Street, River Forest, IL 60305, USA
4
Center for Gender-Specific Medicine, Gender Prevention and Health Section, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy
5
Department of Neuroscience and Rehabilitation, University of Ferrara, via Luigi Borsari 46, 44121 Ferrara, Italy
6
Research Coordination and Support Service, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy
*
Author to whom correspondence should be addressed.
Current address: Research Coordination and Support Service, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
Int. J. Mol. Sci. 2025, 26(17), 8242; https://doi.org/10.3390/ijms26178242 (registering DOI)
Submission received: 5 July 2025 / Revised: 20 August 2025 / Accepted: 22 August 2025 / Published: 25 August 2025
(This article belongs to the Special Issue New Insights in Natural Bioactive Compounds: 3rd Edition)

Abstract

Capsaicin, the main pungent component of chili peppers, exhibits several bioactive properties, such as modulation of adipogenesis and inhibition of liver steatosis by reducing cytoplasmic lipid accumulation. However, no evidence is currently available regarding its effect on the membrane fatty acid remodeling. In this work, we focused on the HepG2 cell model, commonly employed for hepatotoxicity, to examine the lipidome changes after treatment with capsaicin (10 µM), and its combination with oleic acid (100 µM), following the effects after 1.5, 3, and 24 h. In addition, cell viability, lipid accumulation, and secretion of inflammatory mediators were assessed. Notably, the combination of capsaicin with oleic acid completely reverted the correlation between cytokine/chemokine levels and omega-6/omega-3 fatty acids compared to capsaicin alone. Additionally, the combined treatment influenced the protective effect of capsaicin against polyunsaturated fatty acids, as investigated through biomimetic experiments.
Keywords: membrane fatty acid remodeling; capsaicin; oleic acid; inflammatory mediators; lipidome; PUFA; liposome models; biomimetic experiments membrane fatty acid remodeling; capsaicin; oleic acid; inflammatory mediators; lipidome; PUFA; liposome models; biomimetic experiments

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MDPI and ACS Style

Tabolacci, C.; Batani, G.; Rossi, S.; Andrei, D.; Bellenghi, M.; Pedini, F.; Mischiati, C.; Scattoni, M.L.; Biffoni, M.; Facchiano, F.; et al. Capsaicin and Its Combination with Oleic Acid Affect Membrane Fatty Acid Remodeling and Cytokine–Chemokine Secretion in HepG2 Cells. Int. J. Mol. Sci. 2025, 26, 8242. https://doi.org/10.3390/ijms26178242

AMA Style

Tabolacci C, Batani G, Rossi S, Andrei D, Bellenghi M, Pedini F, Mischiati C, Scattoni ML, Biffoni M, Facchiano F, et al. Capsaicin and Its Combination with Oleic Acid Affect Membrane Fatty Acid Remodeling and Cytokine–Chemokine Secretion in HepG2 Cells. International Journal of Molecular Sciences. 2025; 26(17):8242. https://doi.org/10.3390/ijms26178242

Chicago/Turabian Style

Tabolacci, Claudio, Gessica Batani, Stefania Rossi, Daniela Andrei, Maria Bellenghi, Francesca Pedini, Carlo Mischiati, Maria Luisa Scattoni, Mauro Biffoni, Francesco Facchiano, and et al. 2025. "Capsaicin and Its Combination with Oleic Acid Affect Membrane Fatty Acid Remodeling and Cytokine–Chemokine Secretion in HepG2 Cells" International Journal of Molecular Sciences 26, no. 17: 8242. https://doi.org/10.3390/ijms26178242

APA Style

Tabolacci, C., Batani, G., Rossi, S., Andrei, D., Bellenghi, M., Pedini, F., Mischiati, C., Scattoni, M. L., Biffoni, M., Facchiano, F., Ferreri, C., & Sansone, A. (2025). Capsaicin and Its Combination with Oleic Acid Affect Membrane Fatty Acid Remodeling and Cytokine–Chemokine Secretion in HepG2 Cells. International Journal of Molecular Sciences, 26(17), 8242. https://doi.org/10.3390/ijms26178242

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