Hamadan University of Medical Sciences Avicenna Journal of Medical Biochemistry 2345-4113 13 2 2025 12 31 Therapeutic and Preventive Effects of Saffron on Modulation of GFAP and Olig2 Gene Expression in Demyelinated Rats 81 88 10.34172/ajmb.2667 EN Leila Khaledi https://orcid.org/0009-0009-5549-1306 Mahnaz Taherianfard https://orcid.org/0000-0002-8819-1619 Mehran Ghaemi Azizollah Khodakaram Tafti Hamid Reza Moradi Maryam Asadian Ghahfarokhi Journal Article 10.34172/ajmb.2667 2025 02 09 2025 10 31 Introduction: Multiple sclerosis (MS) is a condition characterized by the loss of myelin. This study investigated the impact of saffron on the expression of glial fibrillary acidic protein (GFAP) and oligodendrocyte transcription factor (Olig2) genes, as well as its effect on the pathological changes in rats with demyelination induced by cuprizone (CPZ). Methods: A total of 60 male Sprague-Dawley rats (weighing 250±20 g) were randomly assigned to 4 groups: sham, MS control, saffron treatment, and saffron prevention. Demyelination was induced via oral gavage with a suspension of carboxymethyl cellulose (1%) combined with CPZ (0.6%). Blood-brain barrier (BBB) disruption was assessed by measuring Evans blue extravasation using UV-Vis spectrophotometry. The gene expression levels of GFAP and Olig2 were analyzed using real-time polymerase chain reaction (RT-PCR). Statistical analysis was carried out using one-way analysis of variance (ANOVA), with a significance level of P<0.05. Results: Saffron extract significantly (P<0.001) reduced demyelination and pathological changes in CPZ-treated rats and alleviated BBB disruption (P<0.01). Furthermore, saffron extract notably (P<0.05) regulated the expression of Olig2 and GFAP in the hippocampus of CPZ-demyelinated rats. The Olig2 and GFAP gene expression levels in the MS control group was significantly lower than in other groups. Conclusion: The findings of this study suggest that saffron has the potential to improve pathological changes and modulate the expression of Olig2 and GFAP genes in the hippocampus of CPZ-induced demyelinated rats.