Abstract
Scopoletin, a phenolic coumarin derived from many medical or edible plants, is involved in various pharmacological functions. In the present study, we showed that Scopoletin effectively ameliorated experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), through novel regulatory mechanisms involving inhibition of NF-κB activity in dendritic cells (DCs). Scopoletin treatment significantly improved the severity of the disease and prominently decreased inflammation and demyelination of central nervous system (CNS) in EAE mice. Disease alleviation correlated with the downregulation of major histocompatibility complex (MHC) class II, CD80 and CD86, expressed on DCs of CNS or spleens, and the infiltration and polarization of encephalitogenic Th1/Th17 cells. Consistent with the in vivo data, Scopoletin-treated, bone marrow-derived dendritic cells (BM-DCs) exhibited reduced expression of MHC class II and costimulatory molecules (e.g., CD80 and CD86) and reduced NF-κB phosphorylation. These findings, for the first time, demonstrated the ability of Scopoletin to impair DC activation, downregulating pathogenic Th1/Th17 inflammatory cell responses and, eventually, reducing EAE severity. Our study demonstrates new evidence that natural products derived from medical or edible plants, such as Scopoletin, will be valuable in developing a novel therapeutic agent for MS in the future.
Highlights
Multiple sclerosis (MS) is a T-cell-mediated chronic autoimmune disease featured by neuroinflammation and demyelination in the central nervous system (CNS), affecting 2.5 million people worldwide, and the incidence continues to increase (Hemmer et al, 2015)
Vehicle-treated EAE mice demonstrated a progressive increase in disease severity after day 10 p.i., while the Scopoletintreated group showed a marked decrease in mean disease course from day 14 to 20 p.i. (Figure 1A)
These results indicate that Scopoletin effectively suppressed EAE pathogenesis
Summary
Multiple sclerosis (MS) is a T-cell-mediated chronic autoimmune disease featured by neuroinflammation and demyelination in the central nervous system (CNS), affecting 2.5 million people worldwide, and the incidence continues to increase (Hemmer et al, 2015). It was proved that DCs treated with natural compounds or synthetic drugs blocked the inflammatory signal and halted disease development (Ginwala et al, 2016; Kornberg et al, 2018). DC-induced suppression is mainly dependent on inhibiting Th17 cell differentiation or promoting Treg cell generation (Thome et al, 2014a; Thome et al, 2018). It is known that naive CD4+ T cells can develop into various effector subsets containing Th1, Th2, Th17, and Treg cells, etc.; among these, Th17 cells are crucially related to the pathogenesis of MS/EAE (He et al, 2017; Malik et al, 2017). Suppression of the cellular response, Th17 cells in particular, can act as a therapeutic target for controlling autoimmune and inflammatory diseases
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