Patulin inhibits LPS-induced nitric oxide production by suppressing MAPKs signaling pathway

Patulin (PAT) is a natural product isolated from several species of fungi. Here, we evaluated the effect of PAT (62.5-4,000 ng/ml) in lipopolysaccharide (LPS)-activated murine peritoneal macrophages. Cell viability assay showed that PAT at concentrations up to 250 ng/ml did not affect macrophage via...

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Bibliographic Details
Published in:Natural product research 2022-11, Vol.36 (22), p.1-5883
Main Authors: Sales-Neto, José Marreiro de, da Silva, Juliane Santos de França, Carvalho, Deyse Cristina Madruga, Lima, Éssia de Almeida, Cavalcante-Silva, Luiz Henrique Agra, Lettnin, Aline Portantiolo, Votto, Ana Paula de Souza, Vasconcelos, Ulrich, Rodrigues-Mascarenhas, Sandra
Format: Article
Language:English
Subjects:
c-Jun protein
CD69 antigen
Cell viability
Extracellular signal-regulated kinase
IL-1β
Inflammation
Inflammatory response
Interleukins
JNK protein
Kinases
Lipopolysaccharides
Macrophages
MAP kinase
Natural products
Nitric oxide
Nitric-oxide synthase
Patulin
Phosphorylation
Protein kinase
Proteins
Ribonucleic acid
RNA
Signal transduction
Signaling
TLR4 protein
Toll-like receptors
Transcription factors
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Summary:Patulin (PAT) is a natural product isolated from several species of fungi. Here, we evaluated the effect of PAT (62.5-4,000 ng/ml) in lipopolysaccharide (LPS)-activated murine peritoneal macrophages. Cell viability assay showed that PAT at concentrations up to 250 ng/ml did not affect macrophage viability. PAT (250 ng/ml) significantly reduced LPS-induced nitric oxide production (by 98.4%), inducible nitric oxide synthase (iNOS) expression (by 83.5%), and iNOS messenger ribonucleic acid expression (by 100.0%). Moreover, PAT significantly reduced LPS-induced interleukin-1β (by 80.6%), cluster of differentiation (CD) 69 (by 63.1%), and Toll-like receptor (TLR) 4 (by 91.9%) protein expression. Finally, PAT significantly reduced LPS-triggered phosphorylation of all mitogen-activated protein kinases (MAPK) assessed: extracellular signal-regulated kinase (ERK; by 89.5%), c-Jun N-terminal kinase (JNK; by 77.5%), and p38 (by 72.3%). Taken together, these data suggest that PAT downregulates acute inflammatory response, inhibiting nitric oxide production by suppressing CD69-TLR4/ERK-JNK-p38 MAPKs/ /iNOS signaling pathway.
ISSN:1478-6419
1478-6427
DOI:10.1080/14786419.2021.2021516