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姜黄素在多发性硬化症实验模型中的双重作用机制。

Dual Mechanism of Action of Curcumin in Experimental Models of Multiple Sclerosis.

机构信息

Laboratoire des Biomolécules, Venins et Applications Théranostiques (LR20IPT01), Institut Pasteur de Tunis, Université de Tunis El Manar, Tunis 1002, Tunisia.

Laboratoire de Génétique Humaine (LR99ES10), Faculté de Médecine de Tunis, Université de Tunis El Manar, Tunis 2092, Tunisia.

出版信息

Int J Mol Sci. 2022 Aug 4;23(15):8658. doi: 10.3390/ijms23158658.

Abstract

BACKGROUND

Multiple sclerosis (MS) is characterized by a combination of inflammatory and demyelination processes in the spinal cord and brain. Conventional drugs generally target the autoimmune response, without any curative effect. For that reason, there is a great interest in identifying novel agents with anti-inflammatory and myelinating effects, to counter the inflammation and cell death distinctive of the disease.

METHODS AND RESULTS

An in vitro assay showed that curcumin (Cur) at 10 µM enhanced the proliferation of C8-D1A cells and modulated the production of Th1/Th2/Th17 cytokines in the cells stimulated by LPS. Furthermore, two in vivo pathophysiological experimental models were used to assess the effect of curcumin (100 mg/kg). The cuprizone model mimics the de/re-myelination aspect in MS, and the experimental autoimmune encephalomyelitis model (EAE) reflects immune-mediated events. We found that Cur alleviated the neurological symptomatology in EAE and modulated the expression of lymphocytes CD3 and CD4 in the spinal cord. Interestingly, Cur restored motor and behavioral deficiencies, as well as myelination, in demyelinated mice, as indicated by the higher index of luxol fast blue (LFB) and the myelin basic protein (MBP) intensity in the corpus callosum.

CONCLUSIONS

Curcumin is a potential therapeutic agent that can diminish the MS neuroimmune imbalance and demyelination through its anti-inflammatory and antioxidant effects.

摘要

背景

多发性硬化症(MS)的特征是脊髓和大脑中存在炎症和脱髓鞘过程的组合。常规药物通常针对自身免疫反应,没有任何治疗效果。因此,人们非常关注寻找具有抗炎和髓鞘形成作用的新型药物,以对抗疾病特有的炎症和细胞死亡。

方法和结果

体外试验表明,姜黄素(Cur)在 10µM 时增强了 C8-D1A 细胞的增殖,并调节了 LPS 刺激细胞产生的 Th1/Th2/Th17 细胞因子。此外,使用了两种体内病理生理学实验模型来评估姜黄素(100mg/kg)的作用。铜诱导模型模拟了 MS 中的脱髓鞘方面,实验性自身免疫性脑脊髓炎模型(EAE)反映了免疫介导的事件。我们发现 Cur 减轻了 EAE 的神经症状,并调节了脊髓中淋巴细胞 CD3 和 CD4 的表达。有趣的是,Cur 恢复了脱髓鞘小鼠的运动和行为缺陷以及髓鞘形成,这表明胼胝体中的洛索洛芬快速蓝(LFB)指数和髓鞘碱性蛋白(MBP)强度更高。

结论

姜黄素是一种潜在的治疗药物,可通过其抗炎和抗氧化作用减轻 MS 神经免疫失衡和脱髓鞘。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebb8/9369178/1711f791b7c8/ijms-23-08658-g001.jpg

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