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

Bakondi, Edina [Bakondi, Edina (Sejt- és molekulá...), author] Department of Medical Chemistry (UD); Singh, Salam Bhopen*; Hajnády, Zoltán [Hajnády, Zoltán, author] Department of Medical Chemistry (UD); Nagy-Pénzes, Máté [Nagy-Pénzes, Máté, author] Department of Medical Chemistry (UD); Regdon, Zsolt [Regdon, Zsolt (molekuláris biológia), author] Department of Medical Chemistry (UD); Kovács, Katalin [Kovács, Katalin (molekuláris biológia), author] MTA-DE Sejtbiológiai és Jelátviteli Kutatócsoport (UD); Department of Medical Chemistry (UD); Hegedűs, Csaba [Hegedűs, Csaba (Biokémia, molekul...), author] Department of Medical Chemistry (UD); Madácsy, Tamara [Madácsy, Tamara (sejtélettan), author] First Department of Internal Medicine (USZ / ÁOK); MTA-SZTE Lendület Epitél Sejtek Szignalizáció é... (USZ / ÁOK / I.DIM); Maléth, József [Maléth, József (Gasztroenterológia), author] First Department of Internal Medicine (USZ / ÁOK); MTA-SZTE Lendület Epitél Sejtek Szignalizáció é... (USZ / ÁOK / I.DIM); Hegyi, Péter [Hegyi, Péter (Gasztroenterológia), author] MTA-SZTE Momentum Translational Gastroenterolog... (USZ / ÁOK / I.DIM); Institute for Translational Medicine (UP / UPMS); Translational Medicine Research Group (UP / SZRC); Demény, Máté Á [Demény, Máté Ágoston (Molekuláris biológia), author] MTA-DE Sejtbiológiai és Jelátviteli Kutatócsoport (UD); Department of Medical Chemistry (UD); Nagy, T [Nagy, Tibor (Tömegspektrometria), author] Department of Applied Chemistry (UD / IChem); Kéki, S. [Kéki, Sándor (kémia), author] Department of Applied Chemistry (UD / IChem); Szabó, Éva ✉ [Szabó, Éva (dermatológia), author] Department of Dermatology (UD); Virág, László ✉ [Virág, László (Sejtbiológia), author] Department of Medical Chemistry (UD)

English Scientific Article (Journal Article)
Published: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 1661-6596 1422-0067 20 (17) Paper: 4308 , 18 p. 2019
  • SJR Scopus - Catalysis: Q1
Identifiers
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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2020-04-05 15:31