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Antcin K targets NLRP3 to suppress neuroinflammation and improve the neurological behaviors of mice with depression.
- Source :
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International immunopharmacology [Int Immunopharmacol] 2023 Apr; Vol. 117, pp. 109908. Date of Electronic Publication: 2023 Mar 10. - Publication Year :
- 2023
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Abstract
- Aim: We aimed to explored the role of Antcin K in resisting depression and its targets.<br />Methods: LPS/IFN-γwas used to induce the activation of microglial BV2 cells. Following Antcin K pretreatment, the proportion of M1 cells was determined using flow cytometry (FCM), the expression of cytokines was measured through ELISA, and that of CDb and NLRP3 was analyzed by cell fluorescence staining. The protein levels were detected by Western-blot assay. After NLRP3 was knocked down in BV2 cells (BV2-nlrp3 <superscript>-/-</superscript> ), the M1 polarization level was detected with Antcin K treatment. The targeted binding relation of Antcin K with NLRP3 was confirmed through small molecule-protein docking and co-immunoprecipitation assay. The chronic unpredictable stress model (CUMS) was constructed to mimic the depression mice. After the administration of Antcin K, the neurological behavior of CUMS mice were detected by open-field test (OFT), elevated plus maze, forced swimming test (FST), and tail suspension test (TST). In addition, the expression of CD11b and IBA-1 was detected through histochemical staining, and the tissue pathological changes were detected by H&E staining.<br />Results: Antcin K suppressed the M1 polarization of BV2 cells and reduced the expression of inflammatory factors. Meanwhile, NLRP3 exhibited targeted binding relation with Antcin K, and Antcin K lost its effect after NLRP3 knockdown. In the CUMS mouse model, Antcin K improved the depression status and neurological behaviors in mice, and decreased central neuroinflammation and microglial cell polarization.<br />Conclusion: Antcin K targets NLRP3 to suppress microglial cell polarization, alleviate central inflammation in mice and improve their neurological behaviors.<br />Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2023. Published by Elsevier B.V.)
Details
- Language :
- English
- ISSN :
- 1878-1705
- Volume :
- 117
- Database :
- MEDLINE
- Journal :
- International immunopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 37012885
- Full Text :
- https://doi.org/10.1016/j.intimp.2023.109908