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橙皮苷可改善多发性硬化症小鼠模型的免疫结果并减轻神经炎症。

Hesperidin ameliorates immunological outcome and reduces neuroinflammation in the mouse model of multiple sclerosis.

作者信息

Haghmorad Dariush, Mahmoudi Mohammad Bagher, Salehipour Zohreh, Jalayer Zoleikha, Momtazi Brojeni Amir Abbas, Rastin Maryam, Kokhaei Parviz, Mahmoudi Mahmoud

机构信息

Department of Laboratory Sciences, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran; Department of Immunology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran.

Department of Genetics, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.

出版信息

J Neuroimmunol. 2017 Jan 15;302:23-33. doi: 10.1016/j.jneuroim.2016.11.009. Epub 2016 Nov 26.

Abstract

Multiple sclerosis (MS) is the most abundant central nervous system (CNS) inflammatory disease, which is due to the reaction of auto reactive T cells with own myelin proteins, leading to physical disorder and paralysis among people suffering the disease. Hesperidin, a flavanone glycoside found abundantly in citrus fruits possesses a wide range of pharmacological properties including potential anti-inflammatory and anti-cancer effects. This study was designed to reveal the molecular and cellular mechanisms underlying the effect of hesperidin on MS alleviation. Female C57BL/6 mice were immunized with MOG. Clinical scores and other parameters were monitored daily for the 21days. At the end of the period, brain/spinal cord histology was performed to measure lymphocyte infiltration; T-cell profiles were determined through ELISA, flow cytometry, and real-time PCR. Transcription factor expression levels in the CNS were assessed using real-time PCR; T cell differentiation was evaluated via flow cytometry. The results demonstrated that hesperidin inhibited development of EAE. Histological studies revealed limited leukocyte infiltration into the CNS. Hesperidin increased Treg cells production of interleukin IL-10 and transforming growth factor (TGF)-β, but concurrently resulted in a significant reduction in production of IL-17 and IL-6. Flow cytometry revealed there were also significant decreases in the percentages of Th17 cells, as well as significant increase in percentages of Treg cells in the spleen and lymph nodes. Real-time PCR results indicated hesperidin treatment reduced ROR-γt factor expression, but enhanced Foxp3 expression. Collectively, these results demonstrated that hesperidin could reduce the incidence and severity of disease.

摘要

多发性硬化症(MS)是最常见的中枢神经系统(CNS)炎性疾病,它是由自身反应性T细胞与自身髓磷脂蛋白发生反应引起的,会导致患病者出现身体功能紊乱和瘫痪。橙皮苷是一种在柑橘类水果中大量存在的黄酮苷,具有广泛的药理特性,包括潜在的抗炎和抗癌作用。本研究旨在揭示橙皮苷缓解MS的分子和细胞机制。用髓鞘少突胶质细胞糖蛋白(MOG)对雌性C57BL/6小鼠进行免疫。在21天内每天监测临床评分和其他参数。在该时间段结束时,进行脑/脊髓组织学检查以测量淋巴细胞浸润;通过酶联免疫吸附测定(ELISA)、流式细胞术和实时聚合酶链反应(PCR)确定T细胞谱。使用实时PCR评估中枢神经系统中转录因子的表达水平;通过流式细胞术评估T细胞分化。结果表明,橙皮苷抑制了实验性自身免疫性脑脊髓炎(EAE)的发展。组织学研究显示白细胞向中枢神经系统的浸润有限。橙皮苷增加了调节性T细胞(Treg)白细胞介素IL-10和转化生长因子(TGF)-β的产生,但同时导致IL-17和IL-6的产生显著减少。流式细胞术显示,脾脏和淋巴结中辅助性T细胞17(Th17)细胞的百分比也显著降低,而Treg细胞的百分比则显著增加。实时PCR结果表明,橙皮苷处理降低了维甲酸相关孤儿受体γt(ROR-γt)因子的表达,但增强了叉头框蛋白3(Foxp3)的表达。总体而言,这些结果表明橙皮苷可以降低疾病的发病率和严重程度。

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