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Spilanthol Inhibits Inflammatory Transcription Factors and iNOS Expression in Macrophages and Exerts Anti-inflammatory Effects in Dermatitis and Pancreatitis

Activated macrophages upregulate inducible nitric oxide synthase (iNOS) leading to the profuse production of nitric oxide (NO) and, eventually, tissue damage. Using macrophage NO production as a biochemical marker of inflammation, we tested different parts (flower, leaf, and stem) of the medicinal p...

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Autores principales: Bakondi, Edina, Singh, Salam Bhopen, Hajnády, Zoltán, Nagy-Pénzes, Máté, Regdon, Zsolt, Kovács, Katalin, Hegedűs, Csaba, Madácsy, Tamara, Maléth, József, Hegyi, Péter, Demény, Máté Á., Nagy, Tibor, Kéki, Sándor, Szabó, Éva, Virág, László
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6747447/
https://www.ncbi.nlm.nih.gov/pubmed/31484391
http://dx.doi.org/10.3390/ijms20174308
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author Bakondi, Edina
Singh, Salam Bhopen
Hajnády, Zoltán
Nagy-Pénzes, Máté
Regdon, Zsolt
Kovács, Katalin
Hegedűs, Csaba
Madácsy, Tamara
Maléth, József
Hegyi, Péter
Demény, Máté Á.
Nagy, Tibor
Kéki, Sándor
Szabó, Éva
Virág, László
author_facet Bakondi, Edina
Singh, Salam Bhopen
Hajnády, Zoltán
Nagy-Pénzes, Máté
Regdon, Zsolt
Kovács, Katalin
Hegedűs, Csaba
Madácsy, Tamara
Maléth, József
Hegyi, Péter
Demény, Máté Á.
Nagy, Tibor
Kéki, Sándor
Szabó, Éva
Virág, László
author_sort Bakondi, Edina
collection PubMed
description Activated macrophages upregulate inducible nitric oxide synthase (iNOS) leading to the profuse production of nitric oxide (NO) and, eventually, tissue damage. Using macrophage NO production as a biochemical marker of inflammation, we tested different parts (flower, leaf, and stem) of the medicinal plant, Spilanthes acmella. We found that extracts prepared from all three parts, especially the flowers, suppressed NO production in RAW macrophages in response to interferon-γ and lipopolysaccharide. Follow up experiments with selected bioactive molecules from the plant (α-amyrin, β-caryophylline, scopoletin, vanillic acid, trans-ferulic acid, and spilanthol) indicated that the N-alkamide, spilanthol, is responsible for the NO-suppressive effects and provides protection from NO-dependent cell death. Spilanthol reduced the expression of iNOS mRNA and protein and, as a possible underlying mechanism, inhibited the activation of several transcription factors (NFκB, ATF4, FOXO1, IRF1, ETS, and AP1) and sensitized cells to downregulation of Smad (TF array experiments). The iNOS inhibitory effect translated into an anti-inflammatory effect, as demonstrated in a phorbol 12-myristate 13-acetate-induced dermatitis and, to a smaller extent, in cerulein-induced pancreatitis. In summary, we demonstrate that spilanthol inhibits iNOS expression, NO production and suppresses inflammatory TFs. These events likely contribute to the observed anti-inflammatory actions of spilanthol in dermatitis and pancreatitis.
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spelling pubmed-67474472019-09-27 Spilanthol Inhibits Inflammatory Transcription Factors and iNOS Expression in Macrophages and Exerts Anti-inflammatory Effects in Dermatitis and Pancreatitis Bakondi, Edina Singh, Salam Bhopen Hajnády, Zoltán Nagy-Pénzes, Máté Regdon, Zsolt Kovács, Katalin Hegedűs, Csaba Madácsy, Tamara Maléth, József Hegyi, Péter Demény, Máté Á. Nagy, Tibor Kéki, Sándor Szabó, Éva Virág, László Int J Mol Sci Article Activated macrophages upregulate inducible nitric oxide synthase (iNOS) leading to the profuse production of nitric oxide (NO) and, eventually, tissue damage. Using macrophage NO production as a biochemical marker of inflammation, we tested different parts (flower, leaf, and stem) of the medicinal plant, Spilanthes acmella. We found that extracts prepared from all three parts, especially the flowers, suppressed NO production in RAW macrophages in response to interferon-γ and lipopolysaccharide. Follow up experiments with selected bioactive molecules from the plant (α-amyrin, β-caryophylline, scopoletin, vanillic acid, trans-ferulic acid, and spilanthol) indicated that the N-alkamide, spilanthol, is responsible for the NO-suppressive effects and provides protection from NO-dependent cell death. Spilanthol reduced the expression of iNOS mRNA and protein and, as a possible underlying mechanism, inhibited the activation of several transcription factors (NFκB, ATF4, FOXO1, IRF1, ETS, and AP1) and sensitized cells to downregulation of Smad (TF array experiments). The iNOS inhibitory effect translated into an anti-inflammatory effect, as demonstrated in a phorbol 12-myristate 13-acetate-induced dermatitis and, to a smaller extent, in cerulein-induced pancreatitis. In summary, we demonstrate that spilanthol inhibits iNOS expression, NO production and suppresses inflammatory TFs. These events likely contribute to the observed anti-inflammatory actions of spilanthol in dermatitis and pancreatitis. MDPI 2019-09-03 /pmc/articles/PMC6747447/ /pubmed/31484391 http://dx.doi.org/10.3390/ijms20174308 Text en © 2019 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bakondi, Edina
Singh, Salam Bhopen
Hajnády, Zoltán
Nagy-Pénzes, Máté
Regdon, Zsolt
Kovács, Katalin
Hegedűs, Csaba
Madácsy, Tamara
Maléth, József
Hegyi, Péter
Demény, Máté Á.
Nagy, Tibor
Kéki, Sándor
Szabó, Éva
Virág, László
Spilanthol Inhibits Inflammatory Transcription Factors and iNOS Expression in Macrophages and Exerts Anti-inflammatory Effects in Dermatitis and Pancreatitis
title Spilanthol Inhibits Inflammatory Transcription Factors and iNOS Expression in Macrophages and Exerts Anti-inflammatory Effects in Dermatitis and Pancreatitis
title_full Spilanthol Inhibits Inflammatory Transcription Factors and iNOS Expression in Macrophages and Exerts Anti-inflammatory Effects in Dermatitis and Pancreatitis
title_fullStr Spilanthol Inhibits Inflammatory Transcription Factors and iNOS Expression in Macrophages and Exerts Anti-inflammatory Effects in Dermatitis and Pancreatitis
title_full_unstemmed Spilanthol Inhibits Inflammatory Transcription Factors and iNOS Expression in Macrophages and Exerts Anti-inflammatory Effects in Dermatitis and Pancreatitis
title_short Spilanthol Inhibits Inflammatory Transcription Factors and iNOS Expression in Macrophages and Exerts Anti-inflammatory Effects in Dermatitis and Pancreatitis
title_sort spilanthol inhibits inflammatory transcription factors and inos expression in macrophages and exerts anti-inflammatory effects in dermatitis and pancreatitis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6747447/
https://www.ncbi.nlm.nih.gov/pubmed/31484391
http://dx.doi.org/10.3390/ijms20174308
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