1,3,4-Oxadiazole Derivative: A Potential Anti-inflammatory and Antioxidant Agent in Experimental Autoimmune Encephalomyelitis.

1,3,4-Oxadiazole derivatives have attracted substantial attention as promising therapeutic agents for neurodegenerative disorders due to their anti-inflammatory and neuroprotective properties. This study specifically examined a 1,3,4-oxadiazole derivative, i.e.,-{[5-(3-bromophenyl)-1, 3, 4-oxadiazol-2-yl] sulfanyl} ethan-1-ol (abbreviated as OX-1), in the context of multiple sclerosis (MS). Currently, approximately 2.8 million individuals worldwide are living with MS. The study demonstrates the therapeutic potential of OX-1 using the experimental autoimmune encephalomyelitis (EAE) model of MS. Neurobehavioral assessments indicate significant improvements in clinical scoring, motor deficits, muscular strength, and locomotor activity in EAE subjects. Imaging test reveal notable improvements in spinal deformity, further supporting the efficacy of the compound. Comprehensive analyses, including antioxidant assays, RT-PCR, and comet assays, confirm that OX-1 effectively reduces oxidative stress, accompanied by a significant decrease in cytokine expression. Histological examinations reveal critical pathological changes in the hippocampus, cortex, eyes, spinal cord, and optic nerve. The data demonstrate that this compound exhibits neuroprotective effects by activating the Nrf2/HO-1 pathway, thereby reducing oxidative stress and enhancing the antioxidant defense system. Additionally, it suppresses the TLR4/NF-κB pathway, significantly lowering pro-inflammatory cytokine production and immune cell infiltration. Furthermore, molecular docking and simulation studies demonstrate the binding interactions and potential modulatory effects of OX-1 on HO-1 and NF-κB. These results emphasize the therapeutic promise of OX-1 in effectively alleviating the clinical signs and symptoms associated with EAE-induced MS.