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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.

Radiation therapy is a major treatment in hepatocellular carcinoma (HCC). Yet, this treatment is ineffective in HCC due to lack of radiosensitivity. For this reason, we examined whether berberine (BBR) might modify the radioresistance of HCC cells. BBR enhances the radiation-induced oxidative stress and apoptosis in Huh7 and HepG2 cells while it protectes HHL-5 cells from radiation damage. To test the importance of Nrf2, a master transcription factor in oxidative damage, the effect of BBR is studied in irradiated Nrf2-deficient cells. BBR fails to induce the radiosensitivity in Nrf2-deficient cells suggesting that Nrf2 is required for the effect of BBR. BBR suppresses the expression of Nrf2 signaling-related proteins (Nrf2, HO-1 and NQO-1) in Huh7 and HepG2 cells, demonstrating that BBR strengthens radiosensitivity via suppressing Nrf2 signaling pathway in HCC cells. Furthermore, experiment using xenografts in nude mice indicated that BBR enhances the growth inhibitory effect of radiation in a Nrf2-dependent manner in vivo . In conclusion, these results suggest that BBR is a promising potential sensitizer for the radiotherapy of HCC.