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Eriodictyol and Homoeriodictyol Improve Memory Impairment in Aβ(25–35)-Induced Mice by Inhibiting the NLRP3 Inflammasome
(1) Alzheimer’s disease (AD) is a neurodegenerative disorder, and it is now widely accepted that neuroinflammation plays a key role in its pathogenesis. Eriodictyol (Eri) and homoeriodictyol (Hom), dihydroflavonoids extracted from a variety of plants, have been confirmed to display a relationship wi...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9025671/ https://www.ncbi.nlm.nih.gov/pubmed/35458684 http://dx.doi.org/10.3390/molecules27082488 |
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author | Guo, Pengli Zeng, Mengnan Wang, Shengchao Cao, Bing Liu, Meng Zhang, Yuhan Jia, Jufang Zhang, Qinqin Zhang, Beibei Wang, Ru Zheng, Xiaoke Feng, Weisheng |
author_facet | Guo, Pengli Zeng, Mengnan Wang, Shengchao Cao, Bing Liu, Meng Zhang, Yuhan Jia, Jufang Zhang, Qinqin Zhang, Beibei Wang, Ru Zheng, Xiaoke Feng, Weisheng |
author_sort | Guo, Pengli |
collection | PubMed |
description | (1) Alzheimer’s disease (AD) is a neurodegenerative disorder, and it is now widely accepted that neuroinflammation plays a key role in its pathogenesis. Eriodictyol (Eri) and homoeriodictyol (Hom), dihydroflavonoids extracted from a variety of plants, have been confirmed to display a relationship with neuroprotection. (2) Methods: An AD mouse model was constructed by intracerebroventricular (ICV) injection of the Aβ(25–35) peptide, and Eri and Hom were administered orally for 4 weeks. UPLC-MS/MS was used to determine whether Eri and Hom cross the blood–brain barrier to exert their therapeutic effects. Histological changes in the brain and levels of Aβ were evaluated, and Y-maze and new object recognition experiments were conducted to assess the effects of Eri and Hom on Aβ(25–35)-induced memory impairment in mice. The levels of oxidative stress and apoptosis in peripheral immune cells and progenitor cells in the hippocampal region were analyzed by flow cytometry and in vitro assays. Western blotting and enzyme-linked immunosorbent assays (ELISA) were used to measure the expression levels of NLRP3 inflammasome-related proteins and inflammatory factors in the brain. The effect of nigericin (an agonist of the NLRP3 inflammasome) on Eri and Hom intervention in LPS-induced N9 microglia was examined using a High Content Screening System. (3) Results: Eri and Hom reduced neuronal damage in mouse brain tissue, decreased Aβ levels in the brain, downregulated oxidative stress and apoptosis levels, and improved learning and memory capacity by crossing the blood–brain barrier to exert its effects. Moreover, Eri and Hom inhibited NLRP3 inflammasome activation and ameliorated immune cell disorder. Furthermore, the effect of Eri and Hom on LPS-induced N9 microglia disappeared after the addition of nigericin to agonize NLRP3 receptors. (4) Conclusions: Eri and Hom improved Aβ(25–35)-induced memory impairment in mice by inhibiting the NLRP3 inflammasome. |
format | Online Article Text |
id | pubmed-9025671 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-90256712022-04-23 Eriodictyol and Homoeriodictyol Improve Memory Impairment in Aβ(25–35)-Induced Mice by Inhibiting the NLRP3 Inflammasome Guo, Pengli Zeng, Mengnan Wang, Shengchao Cao, Bing Liu, Meng Zhang, Yuhan Jia, Jufang Zhang, Qinqin Zhang, Beibei Wang, Ru Zheng, Xiaoke Feng, Weisheng Molecules Article (1) Alzheimer’s disease (AD) is a neurodegenerative disorder, and it is now widely accepted that neuroinflammation plays a key role in its pathogenesis. Eriodictyol (Eri) and homoeriodictyol (Hom), dihydroflavonoids extracted from a variety of plants, have been confirmed to display a relationship with neuroprotection. (2) Methods: An AD mouse model was constructed by intracerebroventricular (ICV) injection of the Aβ(25–35) peptide, and Eri and Hom were administered orally for 4 weeks. UPLC-MS/MS was used to determine whether Eri and Hom cross the blood–brain barrier to exert their therapeutic effects. Histological changes in the brain and levels of Aβ were evaluated, and Y-maze and new object recognition experiments were conducted to assess the effects of Eri and Hom on Aβ(25–35)-induced memory impairment in mice. The levels of oxidative stress and apoptosis in peripheral immune cells and progenitor cells in the hippocampal region were analyzed by flow cytometry and in vitro assays. Western blotting and enzyme-linked immunosorbent assays (ELISA) were used to measure the expression levels of NLRP3 inflammasome-related proteins and inflammatory factors in the brain. The effect of nigericin (an agonist of the NLRP3 inflammasome) on Eri and Hom intervention in LPS-induced N9 microglia was examined using a High Content Screening System. (3) Results: Eri and Hom reduced neuronal damage in mouse brain tissue, decreased Aβ levels in the brain, downregulated oxidative stress and apoptosis levels, and improved learning and memory capacity by crossing the blood–brain barrier to exert its effects. Moreover, Eri and Hom inhibited NLRP3 inflammasome activation and ameliorated immune cell disorder. Furthermore, the effect of Eri and Hom on LPS-induced N9 microglia disappeared after the addition of nigericin to agonize NLRP3 receptors. (4) Conclusions: Eri and Hom improved Aβ(25–35)-induced memory impairment in mice by inhibiting the NLRP3 inflammasome. MDPI 2022-04-12 /pmc/articles/PMC9025671/ /pubmed/35458684 http://dx.doi.org/10.3390/molecules27082488 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Guo, Pengli Zeng, Mengnan Wang, Shengchao Cao, Bing Liu, Meng Zhang, Yuhan Jia, Jufang Zhang, Qinqin Zhang, Beibei Wang, Ru Zheng, Xiaoke Feng, Weisheng Eriodictyol and Homoeriodictyol Improve Memory Impairment in Aβ(25–35)-Induced Mice by Inhibiting the NLRP3 Inflammasome |
title | Eriodictyol and Homoeriodictyol Improve Memory Impairment in Aβ(25–35)-Induced Mice by Inhibiting the NLRP3 Inflammasome |
title_full | Eriodictyol and Homoeriodictyol Improve Memory Impairment in Aβ(25–35)-Induced Mice by Inhibiting the NLRP3 Inflammasome |
title_fullStr | Eriodictyol and Homoeriodictyol Improve Memory Impairment in Aβ(25–35)-Induced Mice by Inhibiting the NLRP3 Inflammasome |
title_full_unstemmed | Eriodictyol and Homoeriodictyol Improve Memory Impairment in Aβ(25–35)-Induced Mice by Inhibiting the NLRP3 Inflammasome |
title_short | Eriodictyol and Homoeriodictyol Improve Memory Impairment in Aβ(25–35)-Induced Mice by Inhibiting the NLRP3 Inflammasome |
title_sort | eriodictyol and homoeriodictyol improve memory impairment in aβ(25–35)-induced mice by inhibiting the nlrp3 inflammasome |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9025671/ https://www.ncbi.nlm.nih.gov/pubmed/35458684 http://dx.doi.org/10.3390/molecules27082488 |
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