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

Abstract

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/Nos2/iNOS signaling pathway.

Patulin Ameliorates Hypertrophied Lipid Accumulation and Lipopolysaccharide-Induced Inflammatory Response by Modulating Mitochondrial Respiration

“…In the present study, RAW 264.7 cells were stimulated with LPS to induce oxidative stress and inflammatory signaling cascade through TLRs on macrophages [ 51 ], and the anti-inflammatory effect of PAT was evaluated. Consistent with our data, PAT demonstrated the potential to suppress NO production by downregulating mitogen-activated protein kinase (MAPK) signaling pathway in LPS-induced murine peritoneal macrophages [ 26 ]. Additionally, PAT treatment inhibited IL-6 and TNF-α expression, as well as the expression of inducible enzyme-encoding genes, such as Cox-2 , under conditions of acute inflammation.…”

“…Patulin (PAT, Figure 1 A) is a mycotoxin produced by various fungal species found in diverse food products, including fruits and vegetables [ 23 ]. Although toxicity studies have investigated the neurological side effects of PAT [ 24 ], some studies suggest that it possesses anticancer and anti-inflammatory effects [ 25 , 26 ]. Notably, PAT is a potent inducer of AMPK signaling in hepatocytes, suggesting that it may have a preventive effect on the development and progression of fatty liver diseases [ 27 ].…”

Piceatannol Protects Brain Endothelial Cell Line (bEnd.3) against Lipopolysaccharide-Induced Inflammation and Oxidative Stress

“…Extensive evidence shows that LPS can activate the MAPK and NF-κB signaling pathways and damage the central nervous system [31,32]. The MAPK signaling cascade is a major regulator involved in oxidative stress and inflammatory response and is also related to the protein expression of iNOS [33]. MAPKs are serine/threonine kinases, mainly including the p38 and c-JNK families [34].…”