Rhein inhibits M1 polarization of BV2 microglia through MAPK/IκB signalling pathway and reduces neurotoxicity caused by neuroinflammation

IF 1.7 4区 医学 Q3 DEVELOPMENTAL BIOLOGY International Journal of Developmental Neuroscience Pub Date : 2024-06-10 DOI:10.1002/jdn.10352
Xin Qin, Bowen Li, Binbin Hu, Juan Huang, Xingfu Tian, Xinyue Zhang, Ye Wang, Wei Huang
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Abstract

Background

Rhein is an anthraquinone compound with anti-inflammatory pharmacological activity. It has been found to play a neuroprotective role in neurological diseases, but the neuroprotective mechanism of rhein remains unclear.

Methods

SH-SY5Y cells serving as neuron-like cells and BV2 microglia were used. The toxicity of rhein on BV2 microglia and the viability of SH-SY5Y cells were measured by CCK-8 assay. The mRNA expression and secretion of pro-inflammatory cytokines were detected by qPCR and ELISA. Iba1, CD86 and pathway signalling protein in BV2 microglia were assessed by Western blot and immunofluorescence. Apoptosis of SH-SY5Y cells exposed to neuroinflammation was analysed through flow cytometry.

Results

Rhein inhibited MAPK/IκB signalling pathways. Further studies revealed that rhein inhibited the production of pro-inflammatory cytokines TNF-α, IL-6, IL-1β and iNOS in BV2 cells and also inhibited the expression of M1 polarization markers Iba1 and CD86 in BV2 cells. Furthermore, rhein reduced the apoptotic rate and restored cell viability of SH-SY5Y cells exposed to neuroinflammation.

Conclusions

Our study demonstrated that rhein inhibited microglia M1 polarization via MAPK/IκB signalling pathway and protected nerve cells through suppressing neuroinflammation.

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Rhein 可通过 MAPK/IκB 信号通路抑制 BV2 小胶质细胞的 M1 极化,降低神经炎症引起的神经毒性。
背景:大黄是一种蒽醌化合物,具有抗炎药理活性。目前已发现它在神经系统疾病中发挥神经保护作用,但大黄酚的神经保护机制仍不清楚:方法:使用 SH-SY5Y 细胞作为神经元样细胞和 BV2 小胶质细胞。方法:采用 SH-SY5Y 细胞作为神经样细胞和 BV2 小胶质细胞,用 CCK-8 法测定流黄素对 BV2 小胶质细胞的毒性和 SH-SY5Y 细胞的活力。通过 qPCR 和 ELISA 检测促炎细胞因子的 mRNA 表达和分泌。通过 Western 印迹和免疫荧光评估了 BV2 小胶质细胞中的 Iba1、CD86 和通路信号蛋白。流式细胞术分析了暴露于神经炎症的 SH-SY5Y 细胞的凋亡情况:结果:大黄酚抑制了 MAPK/IκB 信号通路。进一步研究发现,大黄酚抑制了 BV2 细胞中促炎细胞因子 TNF-α、IL-6、IL-1β 和 iNOS 的产生,还抑制了 BV2 细胞中 M1 极化标志物 Iba1 和 CD86 的表达。此外,流黄素还能降低暴露于神经炎症的 SH-SY5Y 细胞的凋亡率,恢复细胞活力:我们的研究表明,流黄素可通过 MAPK/IκB 信号通路抑制小胶质细胞 M1 极化,并通过抑制神经炎症保护神经细胞。
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来源期刊
CiteScore
3.30
自引率
5.60%
发文量
78
审稿时长
6-12 weeks
期刊介绍: International Journal of Developmental Neuroscience publishes original research articles and critical review papers on all fundamental and clinical aspects of nervous system development, renewal and regeneration, as well as on the effects of genetic and environmental perturbations of brain development and homeostasis leading to neurodevelopmental disorders and neurological conditions. Studies describing the involvement of stem cells in nervous system maintenance and disease (including brain tumours), stem cell-based approaches for the investigation of neurodegenerative diseases, roles of neuroinflammation in development and disease, and neuroevolution are also encouraged. Investigations using molecular, cellular, physiological, genetic and epigenetic approaches in model systems ranging from simple invertebrates to human iPSC-based 2D and 3D models are encouraged, as are studies using experimental models that provide behavioural or evolutionary insights. The journal also publishes Special Issues dealing with topics at the cutting edge of research edited by Guest Editors appointed by the Editor in Chief. A major aim of the journal is to facilitate the transfer of fundamental studies of nervous system development, maintenance, and disease to clinical applications. The journal thus intends to disseminate valuable information for both biologists and physicians. International Journal of Developmental Neuroscience is owned and supported by The International Society for Developmental Neuroscience (ISDN), an organization of scientists interested in advancing developmental neuroscience research in the broadest sense.
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