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Trans-10-hydroxy-2-decenoic acid protects against LPS-induced neuroinflammation through FOXO1-mediated activation of autophagy.
- Source :
- European Journal of Nutrition; Oct2020, Vol. 59 Issue 7, p2875-2892, 18p, 4 Color Photographs, 2 Charts, 4 Graphs
- Publication Year :
- 2020
-
Abstract
- Purpose: Neuroinflammation is thought to be associated with the pathogenesis of a series of neurodegenerative diseases. We have previously reported that royal jelly (RJ) has an anti-inflammatory effect on microglial BV-2 cells. However, components contributing to the effect of RJ were largely unexplored. The aim of this study was to assess whether trans-10-hydroxy-2-decenoic acid (10-HDA), the exclusive fatty acid in RJ, can alleviate neuroinflammation and to further explore the underlying mechanisms. Methods: Immunohistochemistry staining, ELISA, qRT-PCR and Western blot were used to assess the effect of 10-HDA on LPS-induced neuroinflammation both in vivo and in vitro. To determine the extent of inflammatory changes after 10-HDA treatment, RNAseq transcriptomic analysis was conducted. Results: 10-HDA pretreatment significantly reduced the production of pro-inflammatory mediators in LPS-treated C57BL/6J mice and microglial BV-2 cells. 10-HDA inhibited the activation of the TNF-α/NF-κB axis and NLRP3 inflammasome-IL-1β pathway, which may be the anti-neuroinflammatory mechanism of 10-HDA. We also demonstrated that 10-HDA triggered cell autophagy, as evidenced by elevated levels of microtubule-associated protein 1 light chain 3-II (LC3-II) and decreased expression of SQSTM1. More importantly, 10-HDA increased the transcriptional activity of FOXO1 by increasing FOXO1 nuclear localization. Inhibition of FOXO1 and autophagy using chemical inhibitors markedly blunted the effect of 10-HDA on the TNF-α pathway and NLRP3 inflammasome-IL-1β pathway, indicating that 10-HDA alleviates neuroinflammation in BV-2 cells by modulating FOXO1-mediated autophagy. Conclusions: 10-HDA may be a promising agent for various neuroinflammation-associated diseases. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 14366207
- Volume :
- 59
- Issue :
- 7
- Database :
- Complementary Index
- Journal :
- European Journal of Nutrition
- Publication Type :
- Academic Journal
- Accession number :
- 145949047
- Full Text :
- https://doi.org/10.1007/s00394-019-02128-9