Glycyrrhizin Protects Mice Against Experimental Autoimmune Encephalomyelitis by Inhibiting High-Mobility Group Box 1 (HMGB1) Expression and Neuronal HMGB1 Release.
Glycyrrhizin Protects Mice Against Experimental Autoimmune Encephalomyelitis by Inhibiting High-Mobility Group Box 1 (HMGB1) Expression and Neuronal HMGB1 Release.
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甘草甜素通过抑制高迁移率族盒 1 (HMGB1) 表达和神经元 HMGB1 释放来保护小鼠免受实验性自身免疫性脑脊髓炎
DOI：
10.3389/fimmu.2018.01518
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发表时间：
2018
影响因子：
7.3
通讯作者：
Zheng F
中科院分区：
文献类型：
--
作者：
Sun Y;Chen H;Dai J;Wan Z;Xiong P;Xu Y;Han Z;Chai W;Gong F;Zheng F
炎症介质高迁移率族蛋白 1 (HMGB1) 在人类多发性硬化症 (MS) 和小鼠实验性自身免疫性脑脊髓炎 (EAE) 的发病机制中发挥着关键作用。甘草甜素 (GL) 是从甘草根中提取的一种糖缀合三萜化合物，具有抑制 HMGB1 功能的能力；然而，迄今为止，GL 针对 EAE 的功能尚未得到彻底表征。为了确定 GL 作为神经炎症调节剂的益处，我们使用体内研究来检查 GL 对 EAE 的影响以及原代培养的皮质神经元，以研究 GL 对 HMGB1 释放的影响。从发病到疾病高峰期，用 GL 治疗 EAE 小鼠，导致 EAE 严重程度显着减轻，炎症细胞浸润和脱髓鞘减少，肿瘤坏死因子-α (TNF-α)、IFN-γ、IL-17A、IL-6 和转化生长因子-β 1 减少，血清和脊髓匀浆中 IL-4 增加。此外，不同体液中的HMGB1水平降低，伴随着神经元损伤、活化的星形胶质细胞和小胶质细胞以及HMGB1阳性星形胶质细胞和小胶质细胞的减少。 GL 显着逆转原代培养的皮层神经元中由 TNF-α 刺激诱导的 HMGB1 释放到培养基中。综上所述，结果表明GL通过减少HMGB1表达和释放对EAE小鼠具有强大的神经保护作用，因此可用于治疗中枢神经系统炎症性疾病，例如MS。
The inflammatory mediator high-mobility group box 1 (HMGB1) plays a critical role in the pathogenesis of human multiple sclerosis (MS) and mouse experimental autoimmune encephalomyelitis (EAE). Glycyrrhizin (GL), a glycoconjugated triterpene extracted from licorice root, has the ability to inhibit the functions of HMGB1; however, GL’s function against EAE has not been thoroughly characterized to date. To determine the benefit of GL as a modulator of neuroinflammation, we used an in vivo study to examine GL’s effect on EAE along with primary cultured cortical neurons to study the GL effect on HMGB1 release. Treatment of EAE mice with GL from onset to the peak stage of disease resulted in marked attenuation of EAE severity, reduced inflammatory cell infiltration and demyelination, decreased tumor necrosis factor-alpha (TNF-α), IFN-γ, IL-17A, IL-6, and transforming growth factor-beta 1, and increased IL-4 both in serum and spinal cord homogenate. Moreover, HMGB1 levels in different body fluids were reduced, accompanied by a decrease in neuronal damage, activated astrocytes and microglia, as well as HMGB1-positive astrocytes and microglia. GL significantly reversed HMGB1 release into the medium induced by TNF-α stimulation in primary cultured cortical neurons. Taken together, the results indicate that GL has a strong neuroprotective effect on EAE mice by reducing HMGB1 expression and release and thus can be used to treat central nervous system inflammatory diseases, such as MS.
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DOI：
10.1016/j.bbi.2017.11.018
发表时间：
2018-08
期刊：
Brain, behavior, and immunity
影响因子：
--
作者：
Kigerl KA;Lai W;Wallace LM;Yang H;Popovich PG
通讯作者：
Popovich PG
影响因子：
6.2
作者：
Hayakawa, Kazuhide;Arai, Ken;Lo, Eng H.
通讯作者：
Lo, Eng H.
影响因子：
8.8
作者：
Gao H;Danzi MC;Choi CS;Taherian M;Dalby-Hansen C;Ellman DG;Madsen PM;Bixby JL;Lemmon VP;Lambertsen KL;Brambilla R
通讯作者：
Brambilla R
影响因子：
100.3
作者：
Baxter, Alan G.
通讯作者：
Baxter, Alan G.
DOI：
10.1084/jem.170.2.607
发表时间：
1989-08-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hofman FM;Hinton DR;Johnson K;Merrill JE
通讯作者：
Merrill JE