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Biomedicines
Volume 13
Issue 7
10.3390/biomedicines13071774
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Reduction in SH-SY5Y Cell Stress Induced by Corticosterone and Attenuation of the Inflammatory Response in RAW 264.7 Cells Using Endomorphin Analogs

by
Renata Perlikowska
1,*,
Angelika Długosz-Pokorska
1,
Małgorzata Domowicz
2,
Sylwia Grabowicz
1,
Mariusz Stasiołek
2 and
Małgorzata Zakłos-Szyda
3
1
Department of Biomolecular Chemistry, Faculty of Medicine, Medical University of Lodz, Mazowiecka 6/8, 92‑215 Lodz, Poland
2
Department of Neurology, Faculty of Medicine, Medical University of Lodz, Kosciuszki Street 4, 90-419 Lodz, Poland
3
Institute of Molecular and Industrial Biotechnology, Faculty of Biotechnology and Food Sciences, Lodz University of Technology, Stefanowskiego 2/22, 90‑537 Lodz, Poland
*
Author to whom correspondence should be addressed.
Biomedicines 2025, 13(7), 1774; https://doi.org/10.3390/biomedicines13071774
Submission received: 5 June 2025 / Revised: 15 July 2025 / Accepted: 18 July 2025 / Published: 20 July 2025
(This article belongs to the Special Issue New Molecular Insights into the Pathogenesis and Drug Development of Neurodegenerative Diseases: 2nd Edition)
Versions Notes

Abstract

Background: To identify drug candidates that reduce cellular stress, linear peptides known as endomorphin (EM) analogs containing proline surrogates in position 2 were tested in in vitro injury models induced by corticosterone (CORT). Methods: In this study, neuroblastoma (SH-SY5Y) cells were treated with CORT and synthesized peptides, and then the cell viability and morphology, reactive oxygen species production (ROS), mitochondrial membrane potential (ΔΨm), adenosine triphosphate (ATP), and intracellular calcium ion [Ca2+]i levels were evaluated. We also conducted an in-depth analysis of the apoptosis markers using quantitative real-time PCR (qPCR). Finally, we explore the brain-derived neurotrophic factor (BDNF) expression (qPCR) and protein levels (ELI-SA and Western blot). Results: The strongest neuroprotective effect in the CORT-induced stress model was shown by peptide 3 and peptide 7 (in the following sequence Tyr-Inp-Trp-Phe-NH2 and Tyr-Inp-Phe-Phe-NH2, respectively). These peptides significantly improved cell viability and reduced oxidative stress in CORT-treated cells. Conclusions: Their neuroprotective potential appears linked to anti-apoptotic effects, along with in-creased BDNF expression. Moreover, in the lipopolysaccharide (LPS)- and interferon-γ (IFN-γ)-induced damage model in macrophage RAW 264.7 cells, these two peptides reduced the secretion of inflammatory mediators nitric oxide (NO), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6). Peptides exhibiting both neuroprotective and anti-inflammatory properties warrant further investigation as potential therapeutic agents.
Keywords: neuroprotection; opioid peptides; cell injury; neuronal damage; depression; cell lines; inflammation neuroprotection; opioid peptides; cell injury; neuronal damage; depression; cell lines; inflammation

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MDPI and ACS Style

Perlikowska, R.; Długosz-Pokorska, A.; Domowicz, M.; Grabowicz, S.; Stasiołek, M.; Zakłos-Szyda, M. Reduction in SH-SY5Y Cell Stress Induced by Corticosterone and Attenuation of the Inflammatory Response in RAW 264.7 Cells Using Endomorphin Analogs. Biomedicines 2025, 13, 1774. https://doi.org/10.3390/biomedicines13071774

AMA Style

Perlikowska R, Długosz-Pokorska A, Domowicz M, Grabowicz S, Stasiołek M, Zakłos-Szyda M. Reduction in SH-SY5Y Cell Stress Induced by Corticosterone and Attenuation of the Inflammatory Response in RAW 264.7 Cells Using Endomorphin Analogs. Biomedicines. 2025; 13(7):1774. https://doi.org/10.3390/biomedicines13071774

Chicago/Turabian Style

Perlikowska, Renata, Angelika Długosz-Pokorska, Małgorzata Domowicz, Sylwia Grabowicz, Mariusz Stasiołek, and Małgorzata Zakłos-Szyda. 2025. "Reduction in SH-SY5Y Cell Stress Induced by Corticosterone and Attenuation of the Inflammatory Response in RAW 264.7 Cells Using Endomorphin Analogs" Biomedicines 13, no. 7: 1774. https://doi.org/10.3390/biomedicines13071774

APA Style

Perlikowska, R., Długosz-Pokorska, A., Domowicz, M., Grabowicz, S., Stasiołek, M., & Zakłos-Szyda, M. (2025). Reduction in SH-SY5Y Cell Stress Induced by Corticosterone and Attenuation of the Inflammatory Response in RAW 264.7 Cells Using Endomorphin Analogs. Biomedicines, 13(7), 1774. https://doi.org/10.3390/biomedicines13071774

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