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Epiisopiloturine, an Alkaloid from Pilocarpus microphyllus, Attenuates LPS-Induced Neuroinflammation by Interfering in the TLR4/NF-κB-MAPK Signaling Pathway in Microglial Cells

Neuroinflammation is present in the pathophysiological mechanisms of several diseases that affect the central nervous system (CNS). Microglia have a prominent role in initiating and sustaining the inflammatory process. Epiisopiloturine (EPI) is an imidazole alkaloid obtained as a by-product of piloc...

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Autores principales: de Sousa, João Antônio Costa, Azul, Francisco Vinícius Clemente Serra, de Araújo, Ana Bruna, Tomé, Rebeca Colares, Silva, Francisca Raysse Mesquita, de Vasconcelos, Silvânia Maria Mendes, Rios, Francisco José, Leal, Luzia Kalyne Almeida Moreira
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10162877/
https://www.ncbi.nlm.nih.gov/pubmed/37151606
http://dx.doi.org/10.1155/2023/4752502
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author de Sousa, João Antônio Costa
Azul, Francisco Vinícius Clemente Serra
de Araújo, Ana Bruna
Tomé, Rebeca Colares
Silva, Francisca Raysse Mesquita
de Vasconcelos, Silvânia Maria Mendes
Rios, Francisco José
Leal, Luzia Kalyne Almeida Moreira
author_facet de Sousa, João Antônio Costa
Azul, Francisco Vinícius Clemente Serra
de Araújo, Ana Bruna
Tomé, Rebeca Colares
Silva, Francisca Raysse Mesquita
de Vasconcelos, Silvânia Maria Mendes
Rios, Francisco José
Leal, Luzia Kalyne Almeida Moreira
author_sort de Sousa, João Antônio Costa
collection PubMed
description Neuroinflammation is present in the pathophysiological mechanisms of several diseases that affect the central nervous system (CNS). Microglia have a prominent role in initiating and sustaining the inflammatory process. Epiisopiloturine (EPI) is an imidazole alkaloid obtained as a by-product of pilocarpine extracted from Pilocarpus microphyllus (jaborandi) and has shown promising anti-inflammatory and antinociceptive properties. In the present study, we investigated the effects of EPI on the inflammatory response in microglial cells (BV-2 cells) induced by lipopolysaccharide (LPS) and explored putative underlying molecular mechanisms. Cell viability was not affected by EPI (1-100 μg/mL) as assessed by both LDH activity and the MTT test. Pretreatment with EPI (25, 50, and 100 μg/mL) significantly reduced the proinflammatory response induced by LPS, as observed by a decrease in nitrite oxide production and iNOS protein expression. EPI (25 μg/mL) reduced IL-6 and TNF-α production, by 40% and 34%, respectively. However, no changes were observed in the anti-inflammatory IL-10 production. Mechanistically, EPI inhibited the TLR4 expression and phosphorylation of NF-κB p65 and MAPKs (JNK and ERK1/2) induced by LPS, but no changes were observed in TREM2 receptor expression in LPS-stimulated cells. In conclusion, our data demonstrated the potent anti-inflammatory properties of EPI in microglial cells. These effects are associated with the reduction of TLR4 expression and inhibition of intracellular signaling cascades, including NF-κB and MAPKs (JNK and ERK1/2).
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spelling pubmed-101628772023-05-06 Epiisopiloturine, an Alkaloid from Pilocarpus microphyllus, Attenuates LPS-Induced Neuroinflammation by Interfering in the TLR4/NF-κB-MAPK Signaling Pathway in Microglial Cells de Sousa, João Antônio Costa Azul, Francisco Vinícius Clemente Serra de Araújo, Ana Bruna Tomé, Rebeca Colares Silva, Francisca Raysse Mesquita de Vasconcelos, Silvânia Maria Mendes Rios, Francisco José Leal, Luzia Kalyne Almeida Moreira Oxid Med Cell Longev Research Article Neuroinflammation is present in the pathophysiological mechanisms of several diseases that affect the central nervous system (CNS). Microglia have a prominent role in initiating and sustaining the inflammatory process. Epiisopiloturine (EPI) is an imidazole alkaloid obtained as a by-product of pilocarpine extracted from Pilocarpus microphyllus (jaborandi) and has shown promising anti-inflammatory and antinociceptive properties. In the present study, we investigated the effects of EPI on the inflammatory response in microglial cells (BV-2 cells) induced by lipopolysaccharide (LPS) and explored putative underlying molecular mechanisms. Cell viability was not affected by EPI (1-100 μg/mL) as assessed by both LDH activity and the MTT test. Pretreatment with EPI (25, 50, and 100 μg/mL) significantly reduced the proinflammatory response induced by LPS, as observed by a decrease in nitrite oxide production and iNOS protein expression. EPI (25 μg/mL) reduced IL-6 and TNF-α production, by 40% and 34%, respectively. However, no changes were observed in the anti-inflammatory IL-10 production. Mechanistically, EPI inhibited the TLR4 expression and phosphorylation of NF-κB p65 and MAPKs (JNK and ERK1/2) induced by LPS, but no changes were observed in TREM2 receptor expression in LPS-stimulated cells. In conclusion, our data demonstrated the potent anti-inflammatory properties of EPI in microglial cells. These effects are associated with the reduction of TLR4 expression and inhibition of intracellular signaling cascades, including NF-κB and MAPKs (JNK and ERK1/2). Hindawi 2023-04-28 /pmc/articles/PMC10162877/ /pubmed/37151606 http://dx.doi.org/10.1155/2023/4752502 Text en Copyright © 2023 João Antônio Costa de Sousa et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
de Sousa, João Antônio Costa
Azul, Francisco Vinícius Clemente Serra
de Araújo, Ana Bruna
Tomé, Rebeca Colares
Silva, Francisca Raysse Mesquita
de Vasconcelos, Silvânia Maria Mendes
Rios, Francisco José
Leal, Luzia Kalyne Almeida Moreira
Epiisopiloturine, an Alkaloid from Pilocarpus microphyllus, Attenuates LPS-Induced Neuroinflammation by Interfering in the TLR4/NF-κB-MAPK Signaling Pathway in Microglial Cells
title Epiisopiloturine, an Alkaloid from Pilocarpus microphyllus, Attenuates LPS-Induced Neuroinflammation by Interfering in the TLR4/NF-κB-MAPK Signaling Pathway in Microglial Cells
title_full Epiisopiloturine, an Alkaloid from Pilocarpus microphyllus, Attenuates LPS-Induced Neuroinflammation by Interfering in the TLR4/NF-κB-MAPK Signaling Pathway in Microglial Cells
title_fullStr Epiisopiloturine, an Alkaloid from Pilocarpus microphyllus, Attenuates LPS-Induced Neuroinflammation by Interfering in the TLR4/NF-κB-MAPK Signaling Pathway in Microglial Cells
title_full_unstemmed Epiisopiloturine, an Alkaloid from Pilocarpus microphyllus, Attenuates LPS-Induced Neuroinflammation by Interfering in the TLR4/NF-κB-MAPK Signaling Pathway in Microglial Cells
title_short Epiisopiloturine, an Alkaloid from Pilocarpus microphyllus, Attenuates LPS-Induced Neuroinflammation by Interfering in the TLR4/NF-κB-MAPK Signaling Pathway in Microglial Cells
title_sort epiisopiloturine, an alkaloid from pilocarpus microphyllus, attenuates lps-induced neuroinflammation by interfering in the tlr4/nf-κb-mapk signaling pathway in microglial cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10162877/
https://www.ncbi.nlm.nih.gov/pubmed/37151606
http://dx.doi.org/10.1155/2023/4752502
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