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Silybin Alleviates Experimental Autoimmune Encephalomyelitis by Suppressing Dendritic Cell Activation and Th17 Cell Differentiation.

ABSTRACT: Silybin, a peculiar flavonoid compound derived from the fruit and seeds of Silybum marianum, exhibits strong anti-inflammatory activities. In the present study, we found that silybin effectively alleviated experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), via inhibition of dendritic cell (DC) activation and Th17 cell differentiation. Silybin treatment greatly ameliorated the disease severity and significantly declined inflammation and demyelination of the central nervous system (CNS) of EAE mice. Consistent with the disease development, silybin-treated bone marrow-derived DCs (BM-DCs) exhibited reduced costimulatory molecules (e.g., CD80 and CD86) and MHC II expression. These results demonstrated the distinguished bioactivity of silybin for suppressing DC activation, inhibiting pathogenic Th17 inflammatory cell responses, and, eventually, alleviating EAE severity. Taken together, our results show that silybin has high potential for the development of a novel therapeutic agent for the treatment of autoimmune diseases such as MS.

SUBMITTER: Yang HL

PROVIDER: S-EPMC8452861 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:AimsDaphnetin, a coumarin derivative extracted from Daphne odora var. marginata, has been reported to have antiinflammatory and immunosuppressive properties. Our previous study indicated that it was able to remarkably suppress the neuroinflammation and suggested its potential application in treating neuroinflammatory diseases. Multiple sclerosis (MS), a Th cell-mediated autoimmune disease, is the most common inflammatory demyelinating disease of the central nervous system (CNS). We examined whether daphnetin treatment can protect mice against experimental autoimmune encephalomyelitis (EAE), an animal model for MS.MethodsTo assess the effect of daphnetin in neuroinflammatory diseases, the EAE mice were established and treated with daphnetin at 8 mg/kg for 28 days. The severity of neuroinflammation and demyelination in the spinal cords was examined histopathologically. Infiltration of CD4(+) T cells into the CNS was assessed by immunohistochemistry, and the cytokine production was determined by ELISA. Meanwhile, the effect of daphnetin on the activity of dendritic cells (DCs) was evaluated, as assessed by DCs' capability to express surface markers, secrete cytokines, and activate naïve CD4(+) T cells. Furthermore, we explored the molecular mechanisms whereby DAPH regulated DCs' activity and thereby CD4(+) T cell responses.ResultsThe administration of daphnetin markedly alleviated the clinical symptoms of EAE and reduced the CNS inflammation and demyelination in experimental mice. Th1 and Th17 cell responses were profoundly repressed in daphnetin-treated EAE mice. Mechanistically, daphnetin treatment significantly repressed the activation, maturation, and antigen-presenting capability of DCs. NF-κB signaling was significantly reduced in daphnetin-treated DCs, along with a concomitant induction of heme oxygenase-1, a negative regulator of inflammatory signaling.ConclusionsOur findings for the first time demonstrate the property of daphnetin in regulating DCs' function and subsequently Th development. Given the low or absent toxicity associated with daphnetin, our data may suggest a novel safe and effective approach to control autoimmune neuroinflammation.

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Silybin Alleviates Experimental Autoimmune Encephalomyelitis by Suppressing Dendritic Cell Activation and Th17 Cell Differentiation.

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