Targeting Mammalian 5-Lipoxygenase by Dietary Phenolics as an Anti-Inflammatory Mechanism: A Systematic Review

Abstract

5-Lipoxygenase (5-LOX) plays a key role in inflammation through the biosynthesis of leukotrienes and other lipid mediators. Current evidence suggests that dietary (poly)phenols exert a beneficial impact on human health through anti-inflammatory activities. Their mechanisms of action have mostly been associated with the modulation of pro-inflammatory cytokines (TNF-α, IL-1β), prostaglandins (PGE2), and the interaction with NF-κB and cyclooxygenase 2 (COX-2) pathways. Much less is known about the 5-lipoxygenase (5-LOX) pathway as a target of dietary (poly)phenols. This systematic review aimed to summarize how dietary (poly)phenols target the 5-LOX pathway in preclinical and human studies. The number of studies identified is low (5, 24, and 127 human, animal, and cellular studies, respectively) compared to the thousands of studies focusing on the COX-2 pathway. Some (poly)phenolics such as caffeic acid, hydroxytyrosol, resveratrol, curcumin, nordihydroguaiaretic acid (NDGA), and quercetin have been reported to reduce the formation of 5-LOX eicosanoids in vitro. However, the in vivo evidence is inconclusive because of the low number of studies and the difficulty of attributing effects to (poly)phenols. Therefore, increasing the number of studies targeting the 5-LOX pathway would largely expand our knowledge on the anti-inflammatory mechanisms of (poly)phenols.

Curcumin and Wnt/β‑catenin signaling in exudative age‑related macular degeneration (Review)

“…In vitro biochemical have studies revealed that the COX-2 pathway catalyzes the oxidation of the 5-lipoxygenase (5-LOX) product 5S-HETE to form a di-endoperoxide ( 158 ) and 5-OH-PGH 2 , equivalent to the prostaglandin endoperoxide PGH 2 of the COX-2 pathway ( 159 ). A previous study has suggested that the stimulation of 12/15-lipoxygenase may lead to the dysregulation of the retinal endothelial cell barrier, demonstrated as increased vascular permeability through the involvement of NADPH oxidases and the subsequent activation of VEGF ( 160 ).…”

“…Lipid peroxidation stimulates redox-sensitive inflammatory factors, including the NF-κB pathway, resulting in inflammation during the progression of AMD ( 162 , 163 ). Curcumin may exert beneficial anti-inflammatory effects via the modulation of the 5-LOX pathway ( 159 , 164 ). Curcumin inhibits 5-LOX activity in polymorphonuclear leukocytes and reduces leukotriene C 4 biosynthesis in limb edema and in anaphylaxis animal models ( 165 , 166 ).…”

Anti-Inflammatory and Antiproliferative Properties of Sweet Cherry Phenolic-Rich Extracts

“…Nowadays, it is already accepted that the daily ingestion of phenolic-rich sources is an effective approach to suppress these events, given their capacity to act as antioxidant species, modulate arachidonic acid metabolism (e.g., cyclooxygenase (COX), lipoxygenases and phospholipase A2), interact with pro-inflammatory nuclear factor κ B, decrease the expression of inducible nitric oxide synthase (iNOS) and, thus, promote a healthy state [ 18 , 19 , 20 , 21 , 22 ].…”

Integrated Analysis of Cecal Microbiome and Metabolome Revealed Different Inflammatory Reponses to Salmonella Enterica Serovar Enteritidis Between Reciprocal Crosses of Chicken

“…Furthermore, lysoPCs enhance arachidonic acid (AA) release from membrane phospholipid via phospholipase A 2 (PLA 2 ) in a time-and concentration-dependent manner [36][37][38]. AA is a substrate for the biosynthesis of several groups of lipid mediators collectively termed eicosanoids including prostaglandins (PGs), which were catalyzed by cyclooxygenases-1 (COX-1)/COX-2 [39]. PGs appear in the onset of in ammation and function as pro-in ammatory factors [40].…”