Icariin ameliorates the cuprizone-induced demyelination associated with antioxidation and anti-inflammation

• Published in: Inflammopharmacology 2024-02, Vol.32 (1), p.809-823
• Main Authors: Song, Li-Juan, Han, Qing-Xian, Ding, Zhi-Bin, Liu, Kexin, Zhang, Xiao-Xu, Guo, Min-Fang, Ma, Dong, Wang, Qing, Xiao, Bao-Guo, Ma, Cun-Gen
• Format: Article
• Language: English
• Subjects: Allergology; Anti-Inflammatory Agents - pharmacology; Antioxidants - pharmacology; Biomedical and Life Sciences; Biomedicine; Cuprizone - pharmacology; Cytokines; Demyelinating Diseases - chemically induced; Demyelinating Diseases - drug therapy; Dermatology; Flavonoids; Gastroenterology; Humans; Immunology; NF-E2-Related Factor 2; NF-kappa B; Original Article; Pharmacology/Toxicology; Rheumatology; Toll-Like Receptor 4
• ISSN: 0925-4692; 1568-5608
• DOI: 10.1007/s10787-023-01388-6

The treatment of immunomodulation in multiple sclerosis (MS) can alleviate the severity and relapses. However, it cannot improve the neurological disability of patients due to a lack of myelin protection and regeneration. Therefore, remyelinating therapies may be one of the feasible strategies that can prevent axonal degeneration and restore neurological disability. Natural product icariin (ICA) is a flavonol compound extracted from epimedium flavonoids, which has neuroprotective effects in several models of neurological diseases. Here, we attempt to explore whether ICA has the potential to treat demyelination and its possible mechanisms of action using lipopolysaccharide-treated BV2 microglia, primary microglia, bone marrow-derived macrophages, and cuprizone-induced demyelination model. The indicators of oxidative stress and inflammatory response were evaluated using commercial kits. The results showed that ICA significantly reduced the levels of oxidative intermediates nitric oxide, hydrogen peroxide, malondialdehyde, and inflammatory cytokines TNF-α, IL-1β, and increased the levels of antioxidants superoxide dismutase, catalase, glutathione peroxidase, and anti-inflammatory cytokines IL-10 and TGF-β in vitro cell experiments. In vivo demyelination model, ICA significantly alleviated the behavioral abnormalities and enhanced the integrated optical density/mm 2 of Black Gold II and myelin basic protein myelin staining, accompanied by the inhibition of oxidative stress/inflammatory response. Immunohistochemical staining showed that ICA significantly induced the expression of nuclear factor erythroid derived 2/heme oxygenase-1 (Nrf2/HO-1) and inhibited the expression of toll-like receptor 4/ nuclear factor kappa B (TLR4/NF-κB), which are two key signaling pathways in antioxidant and anti-inflammatory processes. Our results strongly suggest that ICA may be used as a potential agent to treat demyelination via regulating Nrf2/HO-1-mediated antioxidative stress and TLR4/NF-κB-mediated inflammatory responses.