Narciclasine inhibits LPS-induced neuroinflammation by modulating the Akt/IKK/NF-kappa B and JNK signaling pathways

文献类型： 外文期刊

第一作者： Zhao, Dong

作者： Zhao, Dong;Zhang, Li Jun;Huang, Tian Qi;Kim, Joonki;Gu, Ming-Yao;Yang, Hyun Ok;Huang, Tian Qi;Yang, Hyun Ok;Yang, Hyun Ok;Zhao, Dong

作者机构：

关键词： Narciclasine; Akt/IKK/NF-kappa B; JNK pathway; Microglia; Neuroinflammation

期刊名称：PHYTOMEDICINE （ 影响因子：4.268； 五年影响因子：4.152 ）

ISSN： 0944-7113

年卷期： 2021 年 85 卷

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收录情况： SCI

摘要： Background: Neuroinflammation is defined as innate immune system activation in the central nervous system, and is a complex response involved in removing pathogens, toxic components, and dead cells by activating microglial cells. However, over-activated microglia have been implicated in the pathogenesis of neurodegenerative diseases, because they release large amounts of neurotoxic factors. Thus, inhibiting microglial activation may represent an attractive approach for preventing neuroinflammatory disorders. The objective of this study was to investigate the effect of narciclasine (NA) on lipopolysaccharide (LPS)-induced neuroinflammation by evaluating related markers and neurotoxic factors. Methods: BV-2 cells were pre-incubated with NA at 0.1, 0.2, and 0.3 mu M for 1h, and then co-treated with LPS for 12 h. Cellular medium and lysates were measured using a nitric oxide assay, enzyme-link immunosorbent assay (ELISA), western blotting, kinase activity assay, luciferase assay, and immunofluorescence assay. C57BL/6N mice were orally administered NA and intraperitoneally injected with LPS, and the cerebral cortex was examined using western blotting and immunofluorescence assays. Results: NA showed novel pharmacological activity, inhibiting pro-inflammatory factors, including TNF-alpha, IL-6, IL-18, NO, and PGE2, but increasing the anti-inflammatory cytokines IL-10 and TGF-beta 1 in LPS-induced microglial cells. Moreover, NA also attenuated the LPS-induced mRNA and proteins of iNOS and COX-2. The mechanistic study indicated that NA attenuates the secretion of pro-inflammatory factor by down-regulating the Akt/IKK/NF-kappa B and JNK signaling pathways, and directly inhibits the catalytic activity of IKK alpha/beta. Furthermore, we found that NA also reduced the expression of the microglial markers Iba-1, COX-2, and TNF-alpha in the mouse brain. Conclusion: NA inhibits the over-expression of pro-inflammatory factors but it promotes anti-inflammatory cytokines by down-regulating the Akt/IKK/NF-kappa B and JNK signaling pathways in experimental models. Thus, NA may be a potential candidate for relieving neuroinflammation.

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