Abstract

BackgroundMicroglia-mediated neuroinflammation is one of the most prominent characteristics of multiple sclerosis (MS), a chronic demyelination disease. As one of the main active ingredients in Astragali radix, total flavonoids of Astragalus (TFA) has multiple pharmacological effects such as immunomodulation, anti-inflammation and and anti-tumor. However, little is known about whether TFA could inhibit microglia-mediated neuroinflammation in MS. PurposeThis study was aimed to elucidate whether TFA could inhibit microglia-mediated neuroinflammation in MS. Study designIn the present study, we explored the protective effect of TFA on experimental autoimmune encephalomyelitis (EAE), an animal model of MS, in mice for the first time, and discussed its mechanism from the aspect of anti-microglia-mediated neuroinflammation. MethodsThe mice received oral administration of TFA (25 and 50 mg/kg) daily from two days before immunization and continued until day 21 post-immunization. The effect of TFA on EAE in mice and its mechanism were investigated by ELISA, Western blot, real-time PCR, luciferase reporter assay, histopathology and immunohistochemistry. ResultsTFA were shown to alleviate the severity of EAE in mice. It inhibited the excessive activation of microglia both in spinal cords of EAE mice and in LPS-stimulated BV-2 cells, evidenced by weakening the production of inflammatory mediators such as NO, TNF-α, IL-6, and IL-1β markedly at either protein or mRNA level. Further study demonstrated that TFA repressed the phosphorylation, nuclear translocation and transcriptional activity of NFκB, and inhibited the activation of AKT and JNK signaling in BV-2 cells induced by LPS. The agonists of AKT and JNK, anisomycin and SC79, could partly abolish the inhibitory effect of TFA on the production of inflammatory mediators in BV-2 cells induced by LPS. ConclusionsTaken together, our results clarified that TFA inhibited microglia-mediated inflammation in EAE mice probably through deactivating JNK/AKT/NFκB signaling pathways. The novel findings may lay a theoretical foundation for the clinical application of TFA in the treatment of MS.

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