State Key Laboratory of Medical Genomics, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences (CAS), Shanghai 200025, China.
Proc Natl Acad Sci U S A. 2013 Feb 5;110(6):2258-63. doi: 10.1073/pnas.1222426110. Epub 2013 Jan 23.
Eriocalyxin B (EriB), a diterpenoid isolated from Isodon eriocalyx, was previously reported to have antitumor effects via multiple pathways, and these pathways are related to immune responses. In this study, we demonstrated that EriB was efficacious in experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis. Treatment with EriB led to amelioration of EAE, which correlated with reduced spinal cord inflammation and demyelination. EriB treatment abolished encephalitogenic T-cell responses to myelin oligodendrocyte glycoprotein in an adoptive transfer EAE model. The underlying mechanism of EriB-induced effects involved inhibition of T helper (Th) 1 and Th17 cell differentiation through Janus Kinase/Signal Transducer and Activator Of Transcription and Nuclear factor-κB signaling pathways as well as elevation of reactive oxygen species. These findings indicate that EriB exerts potent antiinflammatory effects through selective modulation of pathogenic Th1 and Th17 cells by targeting critical signaling pathways. The study provides insights into the role of EriB as a unique therapeutic agent for the treatment of autoimmune diseases.
从宜昌瑞草中分离得到的二萜 Eriocalyxin B（EriB）先前被报道通过多种途径具有抗肿瘤作用，这些途径与免疫反应有关。在这项研究中，我们证明 EriB 对实验性自身免疫性脑脊髓炎（EAE）有效，EAE 是多发性硬化症的动物模型。EriB 治疗可改善 EAE，与脊髓炎症和脱髓鞘减少相关。EriB 治疗通过 Janus 激酶/信号转导和转录激活因子和核因子-κB 信号通路以及提高活性氧来消除髓鞘少突胶质细胞糖蛋白的致脑炎 T 细胞反应在过继转移 EAE 模型中。EriB 诱导作用的潜在机制涉及通过 Janus 激酶/信号转导和转录激活因子和核因子-κB 信号通路抑制辅助性 T（Th）1 和 Th17 细胞分化，以及提高活性氧。这些发现表明 EriB 通过针对关键信号通路选择性调节致病性 Th1 和 Th17 细胞来发挥强大的抗炎作用。该研究为 EriB 作为治疗自身免疫性疾病的独特治疗剂的作用提供了深入了解。
