Inhibition of the transcription factor c-Jun by the MAPK family, and not the NF-κB pathway, suggests that peanut extract has anti-inflammatory properties.
BACKGROUND
Tumor necrosis factor-α (TNF-α) is involved in inflammatory responses in atherosclerosis. We propose an in vitro cellular assay to evaluate the anti-inflammatory mechanisms of potential modifiers such as food extracts. In the current model we assessed an anti-inflammatory effect of polyphenol-rich peanut extract in lipopolysaccharide (LPS)-induced THP-1 monocytes.


METHODS
THP-1 monocytes were incubated with peanut extract (5, 25, 50 and 100 μg/mL) consisting of 39% flavonols, 37% flavanols and 24% phenolic acid (or BAY 11-7082 (5 μM) as experiment control) for 1 h and then stimulated with LPS (500 ng/mL) for 4 h. Cytotoxicity was measured as lactate dehydrogenase (LDH) activity release. NF-κB and MAPK family were determined by TransAm kit while TNF-α mRNA levels and its mRNA stability by RT-PCR. Intra- and extracellular TNF-α protein was measured by ELISA, and TNF-α converting enzyme (TACE) activity by a fluorimetric assay.


RESULTS
Peanut extract inhibited the maximal LPS-induced extracellular TNF-α protein secretion by 18%, 29% and 47% at 25, 50 and 100 μg/mL, respectively (P<0.05). LPS stimulation revealed that 85% of TNF-α was released extracellularly while 15% remained intracellular. Peanut extract did not modify NF-κB but, instead, reduced c-Jun transcription factor activity (P<0.05), decreased TNF-α mRNA (albeit non-significantly) and had no effect on mRNA stability and TACE activity.


CONCLUSIONS
Polyphenol-rich peanut extract reduces extracellular TNF-α protein by inhibiting c-Jun transcription factor from MAPK family, suggesting an anti-inflammatory effect. The proposed THP-1 monocyte model could be used to assess food extract impact (site and size effects) on the inflammation pathway.
Unitat de Recerca en Lípids i Arteriosclerosi, CIBERDEM, Hospital Universitari Sant Joan, IISPV, Universitat Rovira i Virgili, Reus, Tarragona, Spain.
Úrsula
Ú
Catalán
Sara
S
Fernández-Castillejo
Neus
N
Anglès
Jose Ramón
JR
Morelló
Martí
M
Yebras
Rosa
R
Solà
D051722:ADAM Proteins / Q000378:metabolism; D000072198:ADAM17 Protein; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D010367:Arachis; D002460:Cell Line; D045744:Cell Line, Tumor; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D009000:Monocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D010936:Plant Extracts / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D007770:L-Lactate Dehydrogenase; D048031:JNK Mitogen-Activated Protein Kinases; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human