Huang Kuo-Kuei, Lin Meng-Nan, Hsu Yi-Ling, Lu I-Huang, Pan I-Hong, Yang Jia-Ling
Department of Life Science, Institute of Biotechnology, National Tsing Hua University, Hsinchu 30013, Taiwan.
Department of Pharmacodynamics and Toxicology, Botanical Drug Technology Division, Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute, Hsinchu 30011, Taiwan.
Evid Based Complement Alternat Med. 2019 Mar 14;2019:6797030. doi: 10.1155/2019/6797030. eCollection 2019.
is a traditional Chinese medicine widely used for treating diarrhea, ulceration, and enuresis. Moreover, is effective for cognitive function improvement and nerve regeneration. Multiple sclerosis (MS) is a chronic neuronal inflammatory autoimmune disease that commonly affects young adults in high-latitude regions. The aim of this study was to evaluate the beneficial effects of in an experimental autoimmune encephalomyelitis (EAE) mouse model, which is an extensively used model for human MS. The ethanolic extract of fruit (AO-1) was orally administered to EAE mice. Our results showed AO-1 significantly reduced EAE symptoms. Histopathological analysis showed AO-1 reduced demyelination, inflammation, gliosis, and axonal swelling in the spinal cord. Furthermore, immunohistochemistry and quantitative polymerase chain reaction (qPCR) studies revealed that the infiltration of CD4, CD8 T cells, and CD11b monocytes into the spinal cord decreased in the AO-1-treated group. Mechanistically, the Th1 transcription factor T-bet, Th17 transcription factor retinoic acid receptor-related orphan receptor (RORt), and inflammatory cytokines interferon (IFN)- and interleukin (IL)-17 were reduced in the spinal cords of mice treated with AO-1. The expression levels of T-bet and RORt were also lowered in the spleens of those mice. Further study showed AO-1 inhibited production of IFN-, IL-2, and tumor necrosis factor- from MOG-peptide-stimulated splenocytes. One component isolated from AO-1, yakuchinone A, inhibited IL-17 production and reduced EAE symptoms in the mice. Collectively, our results indicate that AO-1 ameliorated the severity of EAE in mice and may involve the regulation of Th1/Th17 response. warrants further investigation, particularly regarding its clinical benefits for MS.
是一种广泛用于治疗腹泻、溃疡和遗尿的传统中药。此外,它对改善认知功能和神经再生有效。多发性硬化症(MS)是一种慢性神经元炎性自身免疫性疾病,通常影响高纬度地区的年轻人。本研究的目的是评估其在实验性自身免疫性脑脊髓炎(EAE)小鼠模型中的有益作用,该模型是一种广泛用于人类MS的模型。将其果实的乙醇提取物(AO-1)口服给予EAE小鼠。我们的结果表明AO-1显著减轻了EAE症状。组织病理学分析表明AO-1减少了脊髓中的脱髓鞘、炎症、胶质细胞增生和轴突肿胀。此外,免疫组织化学和定量聚合酶链反应(qPCR)研究显示,在AO-1治疗组中,脊髓中CD4、CD8 T细胞和CD11b单核细胞的浸润减少。机制上,在AO-1处理的小鼠脊髓中,Th1转录因子T-bet、Th17转录因子维甲酸受体相关孤儿受体(RORt)以及炎性细胞因子干扰素(IFN)-和白细胞介素(IL)-17减少。这些小鼠脾脏中T-bet和RORt的表达水平也降低。进一步的研究表明AO-1抑制了MOG肽刺激的脾细胞产生IFN-、IL-2和肿瘤坏死因子-。从AO-1中分离出的一种成分,氧化前胡素A,抑制了IL-17的产生并减轻了小鼠的EAE症状。总体而言,我们的结果表明AO-1减轻了小鼠EAE的严重程度,可能涉及Th1/Th17反应的调节。值得进一步研究,特别是关于其对MS的临床益处。