Punicic Acid a Conjugated Linolenic Acid Inhibits TNFα-Induced Neutrophil Hyperactivation and Protects from Experimental Colon Inflammation in Rats

Abstract

BackgroundNeutrophils play a major role in inflammation by releasing large amounts of ROS produced by NADPH-oxidase and myeloperoxidase (MPO). The proinflammatory cytokine TNFα primes ROS production through phosphorylation of the NADPH-oxidase subunit p47phox on Ser345. Conventional anti-inflammatory therapies remain partially successful and may have side effects. Therefore, regulation of neutrophil activation by natural dietary components represents an alternative therapeutic strategy in inflammatory diseases such as inflammatory bowel diseases. The aim of this study was to assess the effect of punicic acid, a conjugated linolenic fatty acid from pomegranate seed oil on TNFα-induced neutrophil hyperactivation in vitro and on colon inflammation in vivo.Methodology and Principal FindingsWe analyzed the effect of punicic acid on TNFα-induced neutrophil upregulation of ROS production in vitro and on TNBS-induced rat colon inflammation. Results show that punicic acid inhibited TNFα-induced priming of ROS production in vitro while preserving formyl-methionyl-leucyl-phenylalanine (fMLP)-induced response. This effect was mediated by the inhibition of Ser345-p47phox phosphorylation and upstream kinase p38MAPK. Punicic acid also inhibited fMLP- and TNFα+fMLP-induced MPO extracellular release from neutrophils. In vivo experiments showed that punicic acid and pomegranate seed oil intake decreased neutrophil-activation and ROS/MPO-mediated tissue damage as measured by F2-isoprostane release and protected rats from TNBS-induced colon inflammation.Conclusions/SignificanceThese data show that punicic acid exerts a potent anti-inflammatory effect through inhibition of TNFα-induced priming of NADPH oxidase by targeting the p38MAPKinase/Ser345-p47phox-axis and MPO release. This natural dietary compound may provide a novel alternative therapeutic strategy in inflammatory diseases such as inflammatory bowel diseases.

Effect of pomegranate juice consumption on biochemical parameters and complete blood count

“…In 2014, Matthaiou et al (3) also determined that glutathione (GSH) levels were increased following two weeks PJ supplementation, indicating that PJ induced beneficial changes in erythrocyte antioxidant concentration. In 2009, Boussetta et al (24) reported that punicic acid, a conjugated unsaturated fatty acid which is derived from the oil of pomegranate seeds, has anti-inflammatory action due to its potential to reduce the activity of neutrophils. Specific tannins in pomegranate also exhibited anti-inflammatory action in mice (25).…”

Effect of dietary pomegranate seed oil and linseed oil on broiler chickens performance and meat fatty acid profile

“…Five CLnA isomers at least have been found in nature: α-eleostearic acid (9c,11t,13t-C18:3n-3), catalpic acid (9c,11t,13c-C18:3n-3), calendic acid (9c,10t,12c-C18:3n-3), jacaric acid (8c,10t,12c-C18:3n-3) and punicic acid (9c,11t,13c-C18:3n-3) (Koba et al, 2007). CLnA isomers have been attributed to exhibit several health benefits that are largely based on animal and in vitro studies (Boussetta et al, 2009;Hontecillas et al, 2009;Hennessy et al, 2011;Saha and Ghos, 2012;Yuan et al, 2014).…”

Hatice Asli Bedel, Nur Tukel Turgut, Aysegul Ugur Kurtoglu, Coskun Usta

“…Also, in an experimental animal study, Binyamin et al proposed that nano-drop formulation of PSO might be considered for the treatment of demyelinating diseases due to its antioxidant effect [29] . It has been proposed that consumption of large amounts of CFA by the Asian and Middle East populations appears to be associated with the lower incidence of inflammatory diseases [30] . Recent studies indicate that PA has a strong antiinflammatory effect through inhibition of tissue necrosis factor α (TNF-α)-induced elevation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and ameliorates colitis in an experimental rat model [30] .…”

“…It has been proposed that consumption of large amounts of CFA by the Asian and Middle East populations appears to be associated with the lower incidence of inflammatory diseases [30] . Recent studies indicate that PA has a strong antiinflammatory effect through inhibition of tissue necrosis factor α (TNF-α)-induced elevation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and ameliorates colitis in an experimental rat model [30] . Likewise, BassaganyaRiera et al provided in vivo molecular proof that PA ameliorated experimental inflammatory bowel disease by modulating T-cell and macrophage function through peroxisome proliferator activated receptors (PPAR-γ) and δ-dependent mechanisms [31] .…”