Neuroprotection of isoorientin against microglia activation induced by lipopolysaccharide via regulating GSK3β, NF-κb and Nrf2/HO-1 pathways.

IF 2.9 4区医学 Q3 IMMUNOLOGY Immunopharmacology and Immunotoxicology Pub Date : 2024-09-08 DOI:10.1080/08923973.2024.2399249

Xiaoqin Tan, Mindie Cao, Yijing Zhao, Lang Yi, Yingui Li, Changhong He, Qing X Li, Yan Dong

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Abstract

Background: Isoorientin (ISO), a flavone C-glycoside, is a glycogen synthase kinase 3β (GSK3β) substrate-competitive inhibitor. ISO has potential in treatment of Alzheimer's disease (AD). An excessive activation of GSK3β can lead to neuroinflammation causing neuronal damage. Microglia cells, as resident immune cells of the central nervous system, mediate neuroinflammation. Here, we studied the effects of ISO on microglial activation to alleviate neuroinflammation.

Methods: Effects of ISO were observed upon the stimulation of mouse microglia BV2 or SIM-A9 cells by lipopolysaccharide (LPS). Lithium chloride (LiCl) was the positive control as a GSK3β inhibitor. The release of TNF-α and NO were analyzed by ELISA and Griess assays, while expressions of COX-2, Iba-1, BDNF, GSK3β, NF-κB p65, IκB, Nrf2 and HO-1 were detected by Western blotting. In the co-culture model of SIM-A9 cells and differentiated SH-SY5Y human neuroblastoma cells, effects of ISO on microglia-mediated neuronal damage were evaluated with the MTS assay.

Results: ISO significantly inhibited the production of TNF-α (p < 0.01), NO (p < 0.001) and the expression of COX-2 (p < 0.01) and Iba-1 (p < 0.05) induced by LPS, and increased BDNF. The cell viability of SH-SY5Y was inhibited by LPS in the co-culture, which was prevented by ISO pretreatment. ISO increased the expression of p-GSK3β (Ser9), IκB and HO-1 in the cytoplasm, decreased NF-κB p65 and increased Nrf2 in the nucleus compared with the LPS group.

Conclusion: ISO attenuated the activation of microglia through regulating the GSK3β, NF-κB and Nrf2/HO-1 signaling pathways to exert neuroprotection.

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伊索连亭通过调节 GSK3β、NF-κb 和 Nrf2/HO-1 通路，对脂多糖诱导的小胶质细胞活化具有神经保护作用。

背景：异连翘素（ISO）是一种黄酮C-糖苷，是一种糖原合酶激酶3β（GSK3β）底物竞争性抑制剂。ISO 具有治疗阿尔茨海默病（AD）的潜力。GSK3β 的过度激活可导致神经炎症，造成神经元损伤。小胶质细胞是中枢神经系统的常驻免疫细胞，可介导神经炎症。在此，我们研究了 ISO 对小胶质细胞活化的影响，以缓解神经炎症：方法：观察 ISO 在脂多糖（LPS）刺激小鼠小胶质细胞 BV2 或 SIM-A9 细胞时的作用。氯化锂（LiCl）作为 GSK3β 抑制剂作为阳性对照。ELISA和Griess检测法分析了TNF-α和NO的释放，Western印迹法检测了COX-2、Iba-1、BDNF、GSK3β、NF-κB p65、IκB、Nrf2和HO-1的表达。在 SIM-A9 细胞和分化的 SH-SY5Y 人神经母细胞瘤细胞的共培养模型中，用 MTS 试验评估了 ISO 对小胶质细胞介导的神经元损伤的影响：结果：ISO 能明显抑制 TNF-α 的产生（p p p p 结论）：ISO通过调节GSK3β、NF-κB和Nrf2/HO-1信号通路减轻了小胶质细胞的激活，从而发挥了神经保护作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Immunopharmacology and Immunotoxicology 医学-毒理学

CiteScore

5.40

自引率

0.00%

发文量

133

审稿时长

4-8 weeks

期刊介绍： The journal Immunopharmacology and Immunotoxicology is devoted to pre-clinical and clinical drug discovery and development targeting the immune system. Research related to the immunoregulatory effects of various compounds, including small-molecule drugs and biologics, on immunocompetent cells and immune responses, as well as the immunotoxicity exerted by xenobiotics and drugs. Only research that describe the mechanisms of specific compounds (not extracts) is of interest to the journal. The journal will prioritise preclinical and clinical studies on immunotherapy of disorders such as chronic inflammation, allergy, autoimmunity, cancer etc. The effects of small-drugs, vaccines and biologics against central immunological targets as well as cell-based therapy, including dendritic cell therapy, T cell adoptive transfer and stem cell therapy, are topics of particular interest. Publications pointing towards potential new drug targets within the immune system or novel technology for immunopharmacological drug development are also welcome. With an immunoscience focus on drug development, immunotherapy and toxicology, the journal will cover areas such as infection, allergy, inflammation, tumor immunology, degenerative disorders, immunodeficiencies, neurology, atherosclerosis and more. Immunopharmacology and Immunotoxicology will accept original manuscripts, brief communications, commentaries, mini-reviews, reviews, clinical trials and clinical cases, on the condition that the results reported are based on original, clinical, or basic research that has not been published elsewhere in any journal in any language (except in abstract form relating to paper communicated to scientific meetings and symposiums).