Spilanthol inhibits inflammatory transcription factors and iNOS expression in macrophages and exerts anti-inflammatory effects in dermatitis and pancreatitis

Edina Bakondi, Salam Bhopen Singh, Zoltán Hajnády, Máté Nagy-Pénzes, Zsolt Regdon, Katalin Kovács, Csaba Hegedűs, Tamara Madácsy, József Maléth, Péter Hegyi, Máté Demény, Tibor Nagy, Sándor Kéki, Éva Szabó, László Virág

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2 Citations (Scopus)

Abstract

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, SpUanthes acmella. We found that extracts prepared from all three parts, especially the flowers, suppressed NO production in RAW macrophages in response to interferon-y and lipopolysaccharide. Follow up experiments with selected bioactive molecules from the plant (oc-amyrin, |3-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 (NFkB, ATF4, FOXOl, IRF1, ETS, and API) 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].

Original languageEnglish
Article number4308
JournalInternational journal of molecular sciences
Volume20
Issue number17
DOIs
Publication statusPublished - Sep 1 2019

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Keywords

  • Dermatitis
  • FOXO1
  • IRF
  • Inducible nitric oxide synthase
  • Macrophage
  • NFkB
  • Nitric oxide
  • Pancreatitis
  • Spilanthol

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

Bakondi, E., Singh, S. B., Hajnády, Z., Nagy-Pénzes, M., Regdon, Z., Kovács, K., Hegedűs, C., Madácsy, T., Maléth, J., Hegyi, P., Demény, M., Nagy, T., Kéki, S., Szabó, É., & Virág, L. (2019). Spilanthol inhibits inflammatory transcription factors and iNOS expression in macrophages and exerts anti-inflammatory effects in dermatitis and pancreatitis. International journal of molecular sciences, 20(17), [4308]. https://doi.org/10.3390/ijms20174308