[Oridonin ameliorates experimental autoimmune encephalomyelitis by inhibiting NF-κB signaling in T lymphocytes]

Objective To investigate the therapeutic effect and mechanism of oridonin on experimental autoimmune encephalomyelitis (EAE). Methods Female C57BL/6 mice were immunized with MOG/CFA to establish EAE model. The mice were randomly divided into EAE control and oridonin treatment groups. The mice were intraperitoneally injected with oridonin [15 mg/(kg.d)] on day 3, 5 and 7 post immunization, and the control group was injected with the same amount of PBS. EAE scores were recorded and the cell infiltration in the spinal cord was observed by HE staining at the peak of the disease. Flow cytometry analysis was used to detect the proliferation and apoptosis of MOG reactive CD4⁺ T cells, and the differentiation of pathogenic T helper type 1 (Th1) cells and Th17 cells. The expression of cytokine IFN-γ and IL-17 were detected by ELISA assay. The expression of nuclear factor κBp65 (NF-κBp65), phosphorylated NF-κBp65 (p-NF-κBp65), and phosphorylated IκB (p-IκB) were detected by Western blot analysis. Results Compared with the control group, the incidence and severity of EAE mice in the oridonin-treated groups was reduced, the onset time was delayed, and the immune cell infiltration in the spinal cord was reduced. In vitro and in vivo experiments showed that oridonin inhibited the proliferation of myelin antigen reactive CD4⁺ T cells and induced their apoptosis. Oridonin inhibited the differentiation of pathogenic Th1 cells and Th17 cells, and the expression of inflammatory cytokines IFN-γ and IL-17. Oridonin inhibited the phosphorylation of IκB and NF-κBp65. Conclusion Oridonin can ameliorate EAE by inhibiting the activation of NF-κB signaling pathway, thereby the proliferation and differentiation of T cells and the secretion of inflammatory factors are inhibited.