艾蒿通过调控 NF-κB 和 MAPK 信号通路抑制脂多糖诱导的神经炎症。

Artemisiae Iwayomogii Herba inhibits lipopolysaccharide-induced neuroinflammation by regulating NF-κB and MAPK signaling pathways.

机构信息

Department of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea.

Department of Medical Science of Meridian, College of Korean Medicine, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea.

出版信息

Phytomedicine. 2021 Apr;84:153501. doi: 10.1016/j.phymed.2021.153501. Epub 2021 Feb 10.

DOI:10.1016/j.phymed.2021.153501

PMID:33626425

Abstract

BACKGROUND

Neuroinflammation plays a major role in the development of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. The regulation of microglia is an efficient therapeutic approach to controlling neuroinflammation.

PURPOSE

In this study, we aimed to determine whether Artemisiae Iwayomogii Herba (AIH), which is herbal medicine traditionally used for inflammation-related disorders, controls neuroinflammatory responses by regulating the microglia-mediated signaling pathway.

METHODS

BV-2 microglial cells were treated with AIH and lipopolysaccharides (LPS), then various pro-inflammatory mediators were analyzed using griess reaction, quantitative reverse-transcription polymerase chain reaction, or western blotting. C57BL/6 J mice were orally administered by AIH for 17 days and intraperitoneally injected with LPS for the last 14 days. The brains were collected and the microglial activation and nucleotide-binding oligomerization domain-, leucine-rich repeat-, and pyrin domain-containing 3 (NLRP3) expression in the cortex and hippocampus were analyzed using immunohistochemistry or western blotting.

RESULTS

In BV-2 microglial cells, we found that AIH inhibited nitric oxide (NO) production induced by LPS. AIH also suppressed the expressions of pro-inflammatory mediators, including inducible NO synthase, cyclooxygenase-2, tumor necrosis factor-α, and interleukin-6. The study also revealed that the effects of AIH are related to the regulation of the nuclear factor kappa B (NF-κB) and the mitogen-activated protein kinase (MAPK) signaling pathway. Additionally, we found that AIH prevented the formation of NLRP3 inflammasomes. Consistent with the results of in vitro studies on the brains of LPS-injected mice, we observed that AIH suppressed microglial activation and NLRP3 expression.

CONCLUSION

Taken together, these results suggest that AIH attenuates neuroinflammation by regulating the NF-κB and MAPK pathways, and it may be used for treating neurological diseases.

摘要

背景

神经炎症在阿尔茨海默病和帕金森病等神经退行性疾病的发展中起主要作用。调节小胶质细胞是控制神经炎症的有效治疗方法。

目的

本研究旨在确定传统上用于炎症相关疾病的草药艾蒿（AIH）是否通过调节小胶质细胞介导的信号通路来控制神经炎症反应。

方法

用 AIH 和脂多糖（LPS）处理 BV-2 小胶质细胞，然后通过格里希反应、定量逆转录聚合酶链反应或 Western blot 分析各种促炎介质。用 AIH 对 C57BL/6 J 小鼠进行 17 天的口服给药，并用 LPS 进行 14 天的腹腔内注射。收集大脑，并用免疫组织化学或 Western blot 分析皮质和海马中的小胶质细胞活化和核苷酸结合寡聚结构域、富含亮氨酸重复序列和吡喃结构域包含 3（NLRP3）的表达。

结果

在 BV-2 小胶质细胞中，我们发现 AIH 抑制了 LPS 诱导的一氧化氮（NO）产生。AIH 还抑制了促炎介质的表达，包括诱导型一氧化氮合酶、环氧化酶-2、肿瘤坏死因子-α和白细胞介素-6。研究还表明，AIH 的作用与核因子 kappa B（NF-κB）和丝裂原活化蛋白激酶（MAPK）信号通路的调节有关。此外，我们发现 AIH 阻止了 NLRP3 炎性体的形成。与 LPS 注射小鼠大脑的体外研究结果一致，我们观察到 AIH 抑制了小胶质细胞活化和 NLRP3 的表达。