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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
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.
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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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