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新型胆酸衍生物的抗神经炎症作用。

Anti-Neuroinflammatory Effects of a Novel Bile Acid Derivative.

机构信息

Department of Chemistry, Biochemistry, and Environmental Protection, Faculty of Sciences, University of Novi Sad, Trg Dositeja Obradovića 3, 21000 Novi Sad, Serbia.

Department of Immunology, Institute for Biological Research "Siniša Stanković"-National Institute of the Republic of Serbia, University of Belgrade, Bulevar Despota Stefana 142, 11108 Belgrade, Serbia.

出版信息

Int J Mol Sci. 2024 Jun 28;25(13):7136. doi: 10.3390/ijms25137136.

DOI:10.3390/ijms25137136
PMID:39000243
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11241333/
Abstract

In the search for novel potent immunomodulatory nuclear factor-erythroid 2 related factor 2 (Nrf2) activators, a derivative of cholic bile acid, SB140, was synthesized. The synthesis of SB140 aimed to increase the electrophilic functionality of the compound, enhancing its ability to activate Nrf2. Effects of SB140 on microglial cells, myeloid-derived cells (MDC), and T cells were explored in the context of (central nervous system) CNS autoimmunity. SB140 potently activated Nrf2 signaling in MDC and microglia. It was efficient in reducing the ability of microglial cells to produce inflammatory nitric oxide, interleukin (IL)-6, and tumor necrosis factor (TNF). Also, SB140 reduced the proliferation of encephalitogenic T cells and the production of their effector cytokines: IL-17 and interferon (IFN)-γ. On the contrary, the effects of SB140 on anti-inflammatory IL-10 production in microglial and encephalitogenic T cells were limited or absent. These results show that SB140 is a potent Nrf2 activator, as well as an immunomodulatory compound. Thus, further research on the application of SB140 in the treatment of neuroinflammatory diseases is warranted. Animal models of multiple sclerosis and other inflammatory neurological disorders will be a suitable choice for such studies.

摘要

在寻找新型有效的免疫调节核因子-红细胞 2 相关因子 2（Nrf2）激活剂时，合成了胆酸衍生物 SB140。合成 SB140 的目的是增加化合物的亲电性，增强其激活 Nrf2 的能力。在（中枢神经系统）CNS 自身免疫的背景下，研究了 SB140 对小胶质细胞、髓样来源细胞（MDC）和 T 细胞的影响。SB140 可强烈激活 MDC 和小胶质细胞中的 Nrf2 信号通路。它能有效地降低小胶质细胞产生炎症性一氧化氮、白细胞介素（IL）-6 和肿瘤坏死因子（TNF）的能力。此外，SB140 还降低了致脑炎 T 细胞的增殖及其效应细胞因子：白细胞介素（IL）-17 和干扰素（IFN）-γ的产生。相反，SB140 对小胶质细胞和致脑炎 T 细胞中抗炎性白细胞介素（IL）-10 的产生作用有限或不存在。这些结果表明，SB140 是一种有效的 Nrf2 激活剂，也是一种免疫调节化合物。因此，进一步研究 SB140 在治疗神经炎症性疾病中的应用是有必要的。多发性硬化症和其他炎症性神经障碍的动物模型将是此类研究的合适选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5298/11241333/1cc0c015b8e1/ijms-25-07136-g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5298/11241333/ac42bc7f848f/ijms-25-07136-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5298/11241333/dd75651e177c/ijms-25-07136-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5298/11241333/26f7e9dd3830/ijms-25-07136-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5298/11241333/1cc0c015b8e1/ijms-25-07136-g007.jpg

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