Bixin Attenuates Experimental Autoimmune Encephalomyelitis by Suppressing TXNIP/NLRP3 Inflammasome Activity and Activating NRF2 Signaling.
Bixin Attenuates Experimental Autoimmune Encephalomyelitis by Suppressing TXNIP/NLRP3 Inflammasome Activity and Activating NRF2 Signaling.
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DOI：
10.3389/fimmu.2020.593368
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发表时间：
2020
影响因子：
7.3
通讯作者：
Xu Y
中科院分区：
文献类型：
--
作者：
Yu Y;Wu DM;Li J;Deng SH;Liu T;Zhang T;He M;Zhao YY;Xu Y
多发性硬化症（MS）是一种自身免疫性退行性疾病，以脱髓鞘和慢性神经炎症为特征。胭脂树红是从胭脂树红种子中分离得到的一种类胡萝卜素，具有多种有效的药理活性，包括抗氧化、抗炎和抗肿瘤特性。然而，胭脂树红对MS的影响尚未得到研究。为了评价胭脂树橙对MS的作用和潜在的分子机制，在C57 BL/6小鼠中建立实验性自身免疫性脑脊髓炎（EAE），通过胃内施用胭脂树橙溶液来治疗。为了评价胭脂树红的分子机制，进行了定量逆转录PCR、蛋白质印迹、免疫组织化学、流式细胞术和酶联免疫吸附测定分析。我们发现，胭脂树橙显着改善EAE小鼠的症状和病理，减少炎症细胞因子TNF-α，IL-6，IL-8，IL-17和IFN-γ的释放，并增加抗炎细胞因子IL-10的表达。胭脂树红通过清除过量的活性氧（ROS），降低EAE小鼠脾脏和中枢神经系统中Th 1和Th 17细胞的比例，抑制小胶质细胞聚集和TXNIP/NLRP 3炎性小体活性。此外，胭脂树红通过激活核因子红细胞2相关因子2（NRF 2）及其下游基因抑制炎症和氧化应激，同时，这些作用在用NRF 2抑制剂ML 385治疗后被抑制。胭脂树红主要通过激活NRF 2信号通路清除ROS来预防EAE小鼠的神经炎症和脱髓鞘。总而言之，我们的结果表明胭脂树橙是治疗多发性硬化症的一种有前途的候选治疗药物。
Multiple sclerosis (MS), an autoimmune and degenerative disease, is characterized by demyelination and chronic neuroinflammation. Bixin is a carotenoid isolated from the seeds of Bixa orellana that exhibits various potent pharmacological activities, including antioxidant, anti-inflammatory, and anti-tumor properties. However, the effects of bixin on MS have not yet been examined. To evaluate the effects and underlying molecular mechanisms of bixin on MS, experimental autoimmune encephalomyelitis (EAE) was established in C57BL/6 mice, which were treated via intragastric administration of bixin solutions. To evaluate the molecular mechanisms of bixin, quantitative reverse-transcription PCR, western blot, immunohistochemistry, flow cytometry, and enzyme-linked immunosorbent assay analyses were performed. We found that bixin significantly improved the symptoms and pathology in EAE mice, reduced the release of inflammatory cytokines TNF-α, IL-6, IL-8, IL-17, and IFN-γ, and increased the expression of the anti-inflammatory cytokine IL-10. And bixin reduced the proportion of Th1 and Th17 cells in the spleen and CNS, and suppressed microglia aggregation, and TXNIP/NLRP3 inflammasome activity by scavenging excessive reactive oxygen species (ROS) in EAE mice. Furthermore, bixin inhibited inflammation and oxidative stress via activating nuclear factor erythroid 2-related factor 2 (NRF2), and its downstream genes in EAE mice, meanwhile, these effects were suppressed upon treatment with an NRF2 inhibitor, ML385. Bixin prevented neuroinflammation and demyelination in EAE mice primarily by scavenging ROS through activation of the NRF2 signaling pathway. Taken together, our results indicate that bixin is a promising therapeutic candidate for treatment of MS.