Protective mechanisms of berberine against experimental autoimmune myocarditis in a rat model
Protective mechanisms of berberine against experimental autoimmune myocarditis in a rat model
复制标题
DOI：
10.1016/j.biopha.2016.02.015
复制
发表时间：
2016-04-01
影响因子：
7.5
通讯作者：
Yuan, Haitao
中科院分区：
文献类型：
--
作者：
Liu, Xuefei;Zhang, Xinghua;Yuan, Haitao
小檗碱是从多种小檗和黄连植物中提取的生物碱衍生物，据报道，新兴研究对免疫介导的疾病具有免疫调节作用。本研究从肌球蛋白诱导的大鼠心肌损伤中研究了小檗碱的作用及其潜在分子机制。用猪心肌肌球蛋白免疫Lewis大鼠以诱导实验性自身免疫性心肌炎（EAM），并用小檗碱和特异性JAK抑制剂AG490治疗作为阳性对照。我们的数据显示，小檗碱和 AG490 均显着减轻 EAM 大鼠受损的心功能和病理生理学严重程度，阻碍高水平的抗心肌肌球蛋白抗体。 EAM 中 Th17 和 Th1 细胞及其细胞因子 IL-17 和 IFN-γ 上调。然而，Th17/Th1反应的过度增加被小檗碱和AG490恢复。我们还检测了 JAK-STAT 通路磷酸化蛋白的表达水平，该通路在 Th17 和 Th1 谱系定型中发挥关键作用。 EAM 中磷酸化 (p)-STAT1、STAT3 和 STAT4 显着增加，而小檗碱则显着减弱它们的过度表达。小檗碱的这种作用与 AG490 阻断作用相当。我们目前的研究表明，小檗碱可以改善 EAM，其机制可能是由于小檗碱差异调节 p-STAT1、p-STAT3 和 p-STAT4 的活性，从而抑制 Th17 和 Th1 细胞分化。 (C) 2016 Elsevier Masson SAS。版权所有。
Berberine, an alkaloid derivative extracted from numerous plants of the general Berberis and Coptis, has been reported to have immunomodulatory effects against immune-mediated disorders in emerging studies. In this study, the effects of berberine and its underlying molecular mechanisms were investigated from the myosin-induced myocardial injury in rats. Lewis rats were immunized with porcine cardiac myosin to induce experimental autoimmune myocarditis (EAM), treated with berberine and specific JAK inhibitor AG490 as a positive control. Our data showed that both berberine and AG490 significantly reduced the impaired cardiac function and the pathophysiological severity, impeded high levels of anti-cardiac myosin antibody of EAM rats. Th17 and Th1 cells as well as their cytokines IL-17 and IFN-gamma were up-regulated in EAM. However, the excessive increase of Th17/Th1 responses was restored by berberine and AG490. We also examined the expression level of phosphorylated proteins of JAK-STAT pathway which has a key role in the Th17 and Th1 lineage commitment. The phosphorylated (p)-STAT1, STAT3 and STAT4 increased significantly in EAM, while berberine notably attenuated their excessive expression. This effect of berberine was equivalent to that of AG490 blockade. Our current study demonstrated that berberine could ameliorate EAM and the underling mechanisms may be due to the fact that berberine differentially modulates the activities of p-STAT1, p-STAT3 and p-STAT4 to suppress Th17 and Th1 cell differentiation. (C) 2016 Elsevier Masson SAS. All rights reserved.