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Open AccessArticle

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

1
Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary
2
MTA-DE Cell Biology and Signaling Research Group, 4032 Debrecen, Hungary
3
First Department of Medicine, University of Szeged, 6720 Szeged, Hungary
4
HAS-USZ Momentum Epithel Cell Signalling and Secretion Research Group, 6720 Szeged, Hungary
5
Department of Public Health, University of Szeged, 6720 Szeged, Hungary
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Institute for Translational Medicine, University of Pécs, Medical School, János Szentágothai Research Centre, 7624 Pécs, Hungary
7
Momentum Gastroenterology Multidisciplinary Research Group, Hungarian Academy of Sciences, University of Szeged, 6720 Szeged, Hungary
8
Department of Applied Chemistry, Faculty of Science and Technology, University of Debrecen, 4032 Debrecen, Hungary
9
Department of Dermatology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(17), 4308; https://doi.org/10.3390/ijms20174308
Received: 31 July 2019 / Revised: 30 August 2019 / Accepted: 1 September 2019 / Published: 3 September 2019
(This article belongs to the Special Issue Natural Anti-inflammatory Agents 2019)
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. View Full-Text
Keywords: dermatitis; pancreatitis; macrophage; nitric oxide; inducible nitric oxide synthase; spilanthol; NFκB; FOXO1; IRF dermatitis; pancreatitis; macrophage; nitric oxide; inducible nitric oxide synthase; spilanthol; NFκB; FOXO1; IRF
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MDPI and ACS Style

Bakondi, E.; Singh, S.B.; Hajnády, Z.; Nagy-Pénzes, M.; Regdon, Z.; Kovács, K.; Hegedűs, C.; Madácsy, T.; Maléth, J.; Hegyi, P.; Demény, M.Á.; Nagy, T.; Kéki, S.; Szabó, É.; Virág, L. Spilanthol Inhibits Inflammatory Transcription Factors and iNOS Expression in Macrophages and Exerts Anti-inflammatory Effects in Dermatitis and Pancreatitis. Int. J. Mol. Sci. 2019, 20, 4308. https://doi.org/10.3390/ijms20174308

AMA Style

Bakondi E, Singh SB, Hajnády Z, Nagy-Pénzes M, Regdon Z, Kovács K, Hegedűs C, Madácsy T, Maléth J, Hegyi P, Demény MÁ, Nagy T, Kéki S, Szabó É, Virág L. Spilanthol Inhibits Inflammatory Transcription Factors and iNOS Expression in Macrophages and Exerts Anti-inflammatory Effects in Dermatitis and Pancreatitis. International Journal of Molecular Sciences. 2019; 20(17):4308. https://doi.org/10.3390/ijms20174308

Chicago/Turabian Style

Bakondi, Edina; Singh, Salam B.; 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. 2019. "Spilanthol Inhibits Inflammatory Transcription Factors and iNOS Expression in Macrophages and Exerts Anti-inflammatory Effects in Dermatitis and Pancreatitis" Int. J. Mol. Sci. 20, no. 17: 4308. https://doi.org/10.3390/ijms20174308

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