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卡诺醇调节实验性自身免疫性脑脊髓炎中的 Th17 细胞分化和小胶质细胞转换。

Carnosol Modulates Th17 Cell Differentiation and Microglial Switch in Experimental Autoimmune Encephalomyelitis.

机构信息

National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, College of Life Sciences, Shaanxi Normal University, Xi'an, China.

Department of Neurology, Thomas Jefferson University, Philadelphia, PA, United States.

出版信息

Front Immunol. 2018 Aug 13;9:1807. doi: 10.3389/fimmu.2018.01807. eCollection 2018.

Abstract

Medicinal plants as a rich pool for developing novel small molecule therapeutic medicine have been used for thousands of years. Carnosol as a bioactive diterpene compound originated from (Rosemary) and , herbs extensively applied in traditional medicine for the treatment of multiple autoimmune diseases (1). In this study, we investigated the therapeutic effects and molecule mechanism of carnosol in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Carnosol treatment significantly alleviated clinical development in the myelin oligodendrocyte glycoprotein (MOG) peptide-induced EAE model, markedly decreased inflammatory cell infiltration into the central nervous system and reduced demyelination. Further, carnosol inhibited Th17 cell differentiation and signal transducer and activator of transcription 3 phosphorylation, and blocked transcription factor NF-κB nuclear translocation. In the passive-EAE model, carnosol treatment also significantly prevented Th17 cell pathogenicity. Moreover, carnosol exerted its therapeutic effects in the chronic stage of EAE, and, remarkably, switched the phenotypes of infiltrated macrophage/microglia. Taken together, our results show that carnosol has enormous potential for development as a therapeutic agent for autoimmune diseases such as MS.

摘要

药用植物作为开发新型小分子治疗药物的丰富源泉,已经被使用了数千年。作为一种源于(迷迭香)和 的生物活性二萜化合物,龙涎香醇在传统医学中被广泛用于治疗多种自身免疫性疾病(1)。在这项研究中,我们研究了龙涎香醇在实验性自身免疫性脑脊髓炎(EAE),即多发性硬化症(MS)动物模型中的治疗效果和分子机制。龙涎香醇治疗显著缓解了髓鞘少突胶质细胞糖蛋白(MOG)肽诱导的 EAE 模型中的临床发展,明显减少了中枢神经系统中的炎症细胞浸润和脱髓鞘。此外,龙涎香醇抑制了 Th17 细胞分化和信号转导和转录激活因子 3 的磷酸化,并阻断了转录因子 NF-κB 的核易位。在被动 EAE 模型中,龙涎香醇治疗也显著阻止了 Th17 细胞的致病性。此外,龙涎香醇在 EAE 的慢性阶段发挥了治疗作用,并且显著改变了浸润的巨噬细胞/小胶质细胞的表型。总之,我们的研究结果表明,龙涎香醇具有作为治疗多发性硬化症等自身免疫性疾病的治疗药物的巨大潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cee/6100297/a72b40dcdf3e/fimmu-09-01807-g001.jpg

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