Co-administration of Naringin and NLRP3 Inhibitor Improves Myelin Repair and Mitigates Oxidative Stress in Cuprizone-Induced Demyelination Model.

BACKGROUND: Naringin and MCC950 as an inflammasome inhibitor have exhibited numerous pharmacological activities, including antioxidant and anti-inflammatory effects. The present study has examined the combined impacts of naringin and MCC950 on the levels of oxidative stress, demyelination, and inflammation in the cuprizone (CPZ)-induced demyelination model. METHODS: In order to induce demyelination, CPZ (0.2% w/w) was added to the normal diet of mice for 42 days. Subsequently, the male C57BL/6 mice received naringin (oral administration), MCC950 (intraperitoneal injection), or their combination for 14 days. Working memory was tested by the Y maze. FluoroMyelin staining, MOG, and GFAP immunostaining assessed the demyelination extent, myelin intensity, and astrocyte activation, respectively. Oxidant/antioxidant biomarkers were measured using colorimetric techniques. The expression levels of MBP, PDGFRα, Olig2, Nrf2, HO-1, NQO-1, GSK3β, IL1α, and IL18 were assessed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). RESULTS: Our results indicated that the co-administration of naringin and MCC950 improved working memory and antioxidant capacity. A significant reduction was found in the extent of demyelination and inflammatory mediatorsin naringin and MCC950-treated mice. In addition, co-administration of naringin and MCC950 elevated the expression levels of pro-myelinating and antioxidant markers. CONCLUSION: These findings indicated improvement of the working memory through co-administration of naringin and MCC950, which might be partly mediated by enhancing antioxidant capacity, promoting remyelination, and mitigating inflammation in the CPZ-induced demyelination model.