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Atractylenolide-III suppresses lipopolysaccharide-induced inflammation via downregulation of toll-like receptor 4 in mouse microglia

Atractylenolide-III (AIII), a sesquiterpene compound isolated from the rhizome of Atractylodes macrocephala, has been reported to have anti-inflammatory effects in the peripheral organs. However, its effects on brain inflammation remain elusive. The present study investigated the effects of AIII on...

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Autores principales: Novianti, Ela, Katsuura, Goro, Kawamura, Namiko, Asakawa, Akihiro, Inui, Akio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8569437/
https://www.ncbi.nlm.nih.gov/pubmed/34765767
http://dx.doi.org/10.1016/j.heliyon.2021.e08269
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author Novianti, Ela
Katsuura, Goro
Kawamura, Namiko
Asakawa, Akihiro
Inui, Akio
author_facet Novianti, Ela
Katsuura, Goro
Kawamura, Namiko
Asakawa, Akihiro
Inui, Akio
author_sort Novianti, Ela
collection PubMed
description Atractylenolide-III (AIII), a sesquiterpene compound isolated from the rhizome of Atractylodes macrocephala, has been reported to have anti-inflammatory effects in the peripheral organs. However, its effects on brain inflammation remain elusive. The present study investigated the effects of AIII on the response to lipopolysaccharide (LPS) in mouse microglia and clarified the underlying mechanism. In this study, treatment of MG6 cells with AIII (100 μM) significantly decreased the mRNA expression and protein levels of toll-like receptor 4 (TLR4). In addition, pretreatment of MG6 cells and primary cultured microglia cells with AIII (100 μM) significantly decreased the mRNA expression and protein levels of tumor necrosis factor-α, interleukin-1β, interleukin-6, inducible nitric oxide synthase, and cyclooxygenase-2 induced by LPS (5 ng/mL) without cytotoxicity. Subsequently, pretreatment with AIII significantly suppressed the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) and c-Jun NH(2)-terminal kinase (JNK) after LPS stimulation in MG6 cells. These results showed that AIII downregulated TLR4 expression, leading to suppression of the p38 MAPK and JNK pathways, which in turn inhibited the production of pro-inflammatory cytokines and enzymes in LPS-stimulated microglia. Our findings, therefore, suggest the potential for AIII as a therapeutic agent for the treatment of brain inflammation, particularly in microglia-associated inflammation.
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spelling pubmed-85694372021-11-10 Atractylenolide-III suppresses lipopolysaccharide-induced inflammation via downregulation of toll-like receptor 4 in mouse microglia Novianti, Ela Katsuura, Goro Kawamura, Namiko Asakawa, Akihiro Inui, Akio Heliyon Research Article Atractylenolide-III (AIII), a sesquiterpene compound isolated from the rhizome of Atractylodes macrocephala, has been reported to have anti-inflammatory effects in the peripheral organs. However, its effects on brain inflammation remain elusive. The present study investigated the effects of AIII on the response to lipopolysaccharide (LPS) in mouse microglia and clarified the underlying mechanism. In this study, treatment of MG6 cells with AIII (100 μM) significantly decreased the mRNA expression and protein levels of toll-like receptor 4 (TLR4). In addition, pretreatment of MG6 cells and primary cultured microglia cells with AIII (100 μM) significantly decreased the mRNA expression and protein levels of tumor necrosis factor-α, interleukin-1β, interleukin-6, inducible nitric oxide synthase, and cyclooxygenase-2 induced by LPS (5 ng/mL) without cytotoxicity. Subsequently, pretreatment with AIII significantly suppressed the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) and c-Jun NH(2)-terminal kinase (JNK) after LPS stimulation in MG6 cells. These results showed that AIII downregulated TLR4 expression, leading to suppression of the p38 MAPK and JNK pathways, which in turn inhibited the production of pro-inflammatory cytokines and enzymes in LPS-stimulated microglia. Our findings, therefore, suggest the potential for AIII as a therapeutic agent for the treatment of brain inflammation, particularly in microglia-associated inflammation. Elsevier 2021-10-27 /pmc/articles/PMC8569437/ /pubmed/34765767 http://dx.doi.org/10.1016/j.heliyon.2021.e08269 Text en © 2021 The Author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Research Article
Novianti, Ela
Katsuura, Goro
Kawamura, Namiko
Asakawa, Akihiro
Inui, Akio
Atractylenolide-III suppresses lipopolysaccharide-induced inflammation via downregulation of toll-like receptor 4 in mouse microglia
title Atractylenolide-III suppresses lipopolysaccharide-induced inflammation via downregulation of toll-like receptor 4 in mouse microglia
title_full Atractylenolide-III suppresses lipopolysaccharide-induced inflammation via downregulation of toll-like receptor 4 in mouse microglia
title_fullStr Atractylenolide-III suppresses lipopolysaccharide-induced inflammation via downregulation of toll-like receptor 4 in mouse microglia
title_full_unstemmed Atractylenolide-III suppresses lipopolysaccharide-induced inflammation via downregulation of toll-like receptor 4 in mouse microglia
title_short Atractylenolide-III suppresses lipopolysaccharide-induced inflammation via downregulation of toll-like receptor 4 in mouse microglia
title_sort atractylenolide-iii suppresses lipopolysaccharide-induced inflammation via downregulation of toll-like receptor 4 in mouse microglia
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8569437/
https://www.ncbi.nlm.nih.gov/pubmed/34765767
http://dx.doi.org/10.1016/j.heliyon.2021.e08269
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