Roflumilast exerted neuroprotective effect in myelin oligodendrocyte glycoprotein35-55 (MOG35-55)-induced experimental autoimmune encephalitis (EAE) model

Zülfinaz Betül Çelik; Caner Günaydın; M. Nusret Çiçekli; Seda Kırmızıkan; Ahmet Altun

Roflumilast exerted neuroprotective effect in myelin oligodendrocyte glycoprotein35-55 (MOG35-55)-induced experimental autoimmune encephalitis (EAE) model

Abstract

In the recent decade, the effect of phosphodiesterase inhibitors (PDEi) in neurological diseases has been extensively investigated. In previous studies, the beneficial effects of PDEi on multiple sclerosis (MS) and oligodendroglial health have been indicated. However, as phosphodiesterase affects many different cellular and molecular pathways on both neurons and glial cells, knowledge about most PDEi is still missing. Roflumilast, a PDE4 inhibitor, is a potent anti-inflammatory drug currently used to treat chronic obstructive pulmonary disease. Recent studies have demonstrated the neuroprotective effects of roflumilast in neurological and immune diseases. Therefore, in this study, we aimed to investigate the effect of roflumilast on the experimental autoimmune encephalitis (EAE)-induced MS model in mice. The effects of roflumilast on the levels of immune semaphorins Sema3A and Sema4D, and pro-inflammatory cytokines, also motor behavior function and myelin integrity were examined. EAE model was created with myelin oligodendrocyte glycoprotein35-55 (MOG35-55) immunization. Animals were treated with roflumilast and FTY720 (Fingolimod hydrochloride) (as positive control) for 28 days and observed for motor impairments. Brain tissue levels of tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), semaphorin 3A (sema3A), semaphorin 4D (sema4D) were determined by enzyme-linked immunosorbent assay (ELISA). Myelin integrity was assessed with luxol fast blue staining. As a result, roflumilast prevented EAE-induced motor impairment and prevented the loss of myelin in the corpus callosum. Additionally, roflumilast suppressed EAE-induced increase in TNF-α, IL-1β, IL-6, and sema3A, sema4D levels in the brain tissue. Our results demonstrated that roflumilast exerts a neuroprotective effect and prevents EAE-induced myelin loss, possibly via decreasing inflammatory cytokines in the brain.

Keywords

References

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Details

Primary Language

English

Subjects

Medical Pharmacology

Journal Section

Research Article

Authors

Zülfinaz Betül Çelik ^*
0000-0003-1390-7309
Türkiye

Caner Günaydın
0000-0002-8304-832X
Türkiye

M. Nusret Çiçekli
0000-0003-4608-3262
Türkiye

Seda Kırmızıkan
0000-0002-5652-778X
Türkiye

Ahmet Altun
0000-0003-2056-8683
Türkiye

Publication Date

June 28, 2025

Submission Date

August 8, 2022

Acceptance Date

September 11, 2022

Published in Issue

Year 2023 Volume: 27 Number: 1

IZ

https://izlik.org/JA96BL65ZL

Cite

RIS / Bibtex

APA

Çelik, Z. B., Günaydın, C., Çiçekli, M. N., Kırmızıkan, S., & Altun, A. (2025). Roflumilast exerted neuroprotective effect in myelin oligodendrocyte glycoprotein35-55 (MOG35-55)-induced experimental autoimmune encephalitis (EAE) model. Journal of Research in Pharmacy, 27(1), 386-394. https://izlik.org/JA96BL65ZL

AMA

1.Çelik ZB, Günaydın C, Çiçekli MN, Kırmızıkan S, Altun A. Roflumilast exerted neuroprotective effect in myelin oligodendrocyte glycoprotein35-55 (MOG35-55)-induced experimental autoimmune encephalitis (EAE) model. J. Res. Pharm. 2025;27(1):386-394. https://izlik.org/JA96BL65ZL

Chicago

Çelik, Zülfinaz Betül, Caner Günaydın, M. Nusret Çiçekli, Seda Kırmızıkan, and Ahmet Altun. 2025. “Roflumilast Exerted Neuroprotective Effect in Myelin Oligodendrocyte Glycoprotein35-55 (MOG35-55)-Induced Experimental Autoimmune Encephalitis (EAE) Model”. Journal of Research in Pharmacy 27 (1): 386-94. https://izlik.org/JA96BL65ZL.

EndNote

Çelik ZB, Günaydın C, Çiçekli MN, Kırmızıkan S, Altun A (June 1, 2025) Roflumilast exerted neuroprotective effect in myelin oligodendrocyte glycoprotein35-55 (MOG35-55)-induced experimental autoimmune encephalitis (EAE) model. Journal of Research in Pharmacy 27 1 386–394.

IEEE

[1]Z. B. Çelik, C. Günaydın, M. N. Çiçekli, S. Kırmızıkan, and A. Altun, “Roflumilast exerted neuroprotective effect in myelin oligodendrocyte glycoprotein35-55 (MOG35-55)-induced experimental autoimmune encephalitis (EAE) model”, J. Res. Pharm., vol. 27, no. 1, pp. 386–394, June 2025, [Online]. Available: https://izlik.org/JA96BL65ZL

ISNAD

Çelik, Zülfinaz Betül - Günaydın, Caner - Çiçekli, M. Nusret - Kırmızıkan, Seda - Altun, Ahmet. “Roflumilast Exerted Neuroprotective Effect in Myelin Oligodendrocyte Glycoprotein35-55 (MOG35-55)-Induced Experimental Autoimmune Encephalitis (EAE) Model”. Journal of Research in Pharmacy 27/1 (June 1, 2025): 386-394. https://izlik.org/JA96BL65ZL.

JAMA

1.Çelik ZB, Günaydın C, Çiçekli MN, Kırmızıkan S, Altun A. Roflumilast exerted neuroprotective effect in myelin oligodendrocyte glycoprotein35-55 (MOG35-55)-induced experimental autoimmune encephalitis (EAE) model. J. Res. Pharm. 2025;27:386–394.

MLA

Çelik, Zülfinaz Betül, et al. “Roflumilast Exerted Neuroprotective Effect in Myelin Oligodendrocyte Glycoprotein35-55 (MOG35-55)-Induced Experimental Autoimmune Encephalitis (EAE) Model”. Journal of Research in Pharmacy, vol. 27, no. 1, June 2025, pp. 386-94, https://izlik.org/JA96BL65ZL.

Vancouver

1.Zülfinaz Betül Çelik, Caner Günaydın, M. Nusret Çiçekli, Seda Kırmızıkan, Ahmet Altun. Roflumilast exerted neuroprotective effect in myelin oligodendrocyte glycoprotein35-55 (MOG35-55)-induced experimental autoimmune encephalitis (EAE) model. J. Res. Pharm. [Internet]. 2025 Jun. 1;27(1):386-94. Available from: https://izlik.org/JA96BL65ZL