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Taxifolin Suppresses Inflammatory Responses of High-Glucose-Stimulated Mouse Microglia by Attenuating the TXNIP–NLRP3 Axis
Type 2 diabetes mellitus is associated with an increased risk of dementia, potentially through multifactorial pathologies, including neuroinflammation. Therefore, there is a need to identify novel agents that can suppress neuroinflammation and prevent cognitive impairment in diabetes. In the present...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10302635/ https://www.ncbi.nlm.nih.gov/pubmed/37375642 http://dx.doi.org/10.3390/nu15122738 |
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author | Iwasa, Masayo Kato, Hisashi Iwashita, Kaori Yamakage, Hajime Kato, Sayaka Saito, Satoshi Ihara, Masafumi Nishimura, Hideo Kawamoto, Atsuhiko Suganami, Takayoshi Tanaka, Masashi Satoh-Asahara, Noriko |
author_facet | Iwasa, Masayo Kato, Hisashi Iwashita, Kaori Yamakage, Hajime Kato, Sayaka Saito, Satoshi Ihara, Masafumi Nishimura, Hideo Kawamoto, Atsuhiko Suganami, Takayoshi Tanaka, Masashi Satoh-Asahara, Noriko |
author_sort | Iwasa, Masayo |
collection | PubMed |
description | Type 2 diabetes mellitus is associated with an increased risk of dementia, potentially through multifactorial pathologies, including neuroinflammation. Therefore, there is a need to identify novel agents that can suppress neuroinflammation and prevent cognitive impairment in diabetes. In the present study, we demonstrated that a high-glucose (HG) environment elevates the intracellular reactive oxygen species (ROS) levels and triggers inflammatory responses in the mouse microglial cell line BV-2. We further found that thioredoxin-interacting protein (TXNIP), a ROS-responsive positive regulator of the nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, was also upregulated, followed by NLRP3 inflammasome activation and subsequent interleukin-1beta (IL-1β) production in these cells. Conversely, caspase-1 was not significantly activated, suggesting the involvement of noncanonical pathways in these inflammatory responses. Moreover, our results demonstrated that taxifolin, a natural flavonoid with antioxidant and radical scavenging activities, suppressed IL-1β production by reducing the intracellular ROS levels and inhibiting the activation of the TXNIP–NLRP3 axis. These findings suggest the novel anti-inflammatory effects of taxifolin on microglia in an HG environment, which could help develop novel strategies for suppressing neuroinflammation in diabetes. |
format | Online Article Text |
id | pubmed-10302635 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-103026352023-06-29 Taxifolin Suppresses Inflammatory Responses of High-Glucose-Stimulated Mouse Microglia by Attenuating the TXNIP–NLRP3 Axis Iwasa, Masayo Kato, Hisashi Iwashita, Kaori Yamakage, Hajime Kato, Sayaka Saito, Satoshi Ihara, Masafumi Nishimura, Hideo Kawamoto, Atsuhiko Suganami, Takayoshi Tanaka, Masashi Satoh-Asahara, Noriko Nutrients Communication Type 2 diabetes mellitus is associated with an increased risk of dementia, potentially through multifactorial pathologies, including neuroinflammation. Therefore, there is a need to identify novel agents that can suppress neuroinflammation and prevent cognitive impairment in diabetes. In the present study, we demonstrated that a high-glucose (HG) environment elevates the intracellular reactive oxygen species (ROS) levels and triggers inflammatory responses in the mouse microglial cell line BV-2. We further found that thioredoxin-interacting protein (TXNIP), a ROS-responsive positive regulator of the nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, was also upregulated, followed by NLRP3 inflammasome activation and subsequent interleukin-1beta (IL-1β) production in these cells. Conversely, caspase-1 was not significantly activated, suggesting the involvement of noncanonical pathways in these inflammatory responses. Moreover, our results demonstrated that taxifolin, a natural flavonoid with antioxidant and radical scavenging activities, suppressed IL-1β production by reducing the intracellular ROS levels and inhibiting the activation of the TXNIP–NLRP3 axis. These findings suggest the novel anti-inflammatory effects of taxifolin on microglia in an HG environment, which could help develop novel strategies for suppressing neuroinflammation in diabetes. MDPI 2023-06-13 /pmc/articles/PMC10302635/ /pubmed/37375642 http://dx.doi.org/10.3390/nu15122738 Text en © 2023 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 | Communication Iwasa, Masayo Kato, Hisashi Iwashita, Kaori Yamakage, Hajime Kato, Sayaka Saito, Satoshi Ihara, Masafumi Nishimura, Hideo Kawamoto, Atsuhiko Suganami, Takayoshi Tanaka, Masashi Satoh-Asahara, Noriko Taxifolin Suppresses Inflammatory Responses of High-Glucose-Stimulated Mouse Microglia by Attenuating the TXNIP–NLRP3 Axis |
title | Taxifolin Suppresses Inflammatory Responses of High-Glucose-Stimulated Mouse Microglia by Attenuating the TXNIP–NLRP3 Axis |
title_full | Taxifolin Suppresses Inflammatory Responses of High-Glucose-Stimulated Mouse Microglia by Attenuating the TXNIP–NLRP3 Axis |
title_fullStr | Taxifolin Suppresses Inflammatory Responses of High-Glucose-Stimulated Mouse Microglia by Attenuating the TXNIP–NLRP3 Axis |
title_full_unstemmed | Taxifolin Suppresses Inflammatory Responses of High-Glucose-Stimulated Mouse Microglia by Attenuating the TXNIP–NLRP3 Axis |
title_short | Taxifolin Suppresses Inflammatory Responses of High-Glucose-Stimulated Mouse Microglia by Attenuating the TXNIP–NLRP3 Axis |
title_sort | taxifolin suppresses inflammatory responses of high-glucose-stimulated mouse microglia by attenuating the txnip–nlrp3 axis |
topic | Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10302635/ https://www.ncbi.nlm.nih.gov/pubmed/37375642 http://dx.doi.org/10.3390/nu15122738 |
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