fucoxanthinol and Inflammation

In recent years, microalgae have drawn increasing attention as a valuable source of functional food ingredients. Intriguingly,

Topics: Animals; Anti-Inflammatory Agents; beta Carotene; Cell Line; Cell Survival; Cyclooxygenase 2; Diatoms; Dinoprostone; Heme Oxygenase-1; Inflammation; Interleukin-6; Lipopolysaccharides; Membrane Proteins; Mice; Microglia; NAD(P)H Dehydrogenase (Quinone); NADPH Oxidases; Nitric Oxide; Nitric Oxide Synthase Type II; Tumor Necrosis Factor-alpha

Palmitoylethanolamide (PEA) is an endogenous lipid mediator with powerful anti-inflammatory and analgesic functions. PEA can be hydrolyzed by a lysosomal enzyme N-acylethanolamine acid amidase (NAAA), which is highly expressed in macrophages and other immune cells. The pharmacological inhibition of NAAA activity is a potential therapeutic strategy for inflammation-related diseases. Fucoxanthinol (FXOH) is a marine carotenoid from brown seaweeds with various beneficial effects. However, the anti-inflammatory effects and mechanism of action of FXOH in lipopolysaccharide (LPS)-stimulated macrophages remain unclear. This study aimed to explore the role of FXOH in the NAAA-PEA pathway and the anti-inflammatory effects based on this mechanism. In vitro results showed that FXOH can directly bind to the active site of NAAA protein and specifically inhibit the activity of NAAA enzyme. In an LPS-induced inflammatory model in macrophages, FXOH pretreatment significantly reversed the LPS-induced downregulation of PEA levels. FXOH also substantially attenuated the mRNA expression of inflammatory factors, including inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), and markedly reduced the production of TNF-α, IL-6, IL-1β, and nitric oxide (NO). Moreover, the inhibitory effect of FXOH on NO induction was significantly abolished by the peroxisome proliferator-activated receptor α (PPAR-α) inhibitor GW6471. All these findings demonstrated that FXOH can prevent LPS-induced inflammation in macrophages, and its mechanisms may be associated with the regulation of the NAAA-PEA-PPAR-α pathway.

Topics: Amides; Amidohydrolases; Animals; Anti-Inflammatory Agents; beta Carotene; Cytokines; Enzyme Inhibitors; Ethanolamines; Inflammation; Lipopolysaccharides; Mice; Nitric Oxide; Oxazoles; Palmitic Acids; PPAR alpha; RAW 264.7 Cells; Tyrosine

Fucoxanthin (Fx) is a marine carotenoid found in edible brown seaweeds. We previously reported that dietary Fx metabolite into fucoxanthinol (FxOH), attenuates the weight gain of white adipose tissue of diabetic/obese KK-Ay mice. In this study, to evaluate anti-diabetic effects of Fx, we investigated improving the effect of insulin resistance on the diabetic model of KK-Ay mice. Furthermore, preventing the effect of FxOH on low-grade chronic inflammation related to oxidative stress was evaluated on 3T3-L1 adipocyte cells and a RAW264.7 macrophage cell co-culture system. A diet containing 0.1% Fx was fed to diabetic model KK-Ay mice for three weeks, then glucose tolerance was observed. Fx diet significantly improved glucose tolerance compared with the control diet group.  In in vitro studies, FxOH showed suppressed tumor necrosis factor-α (TNF-α), and monocyte chemotactic protein-1 (MCP-1) mRNA expression and protein levels in a co-culture of adipocyte and macrophage cells. These findings suggest that Fx ameliorates glucose tolerance in the diabetic model mice. Furthermore, FxOH, a metabolite of Fx, suppresses low-grade chronic inflammation in adipocyte cells.

Topics: 3T3-L1 Cells; Adipocytes; Adipose Tissue, White; Animals; beta Carotene; Blood Glucose; Cell Line; Chemokine CCL2; Diabetes Mellitus, Experimental; Diet; Disease Models, Animal; Inflammation; Insulin Resistance; Macrophages; Mice; Obesity; RNA, Messenger; Tumor Necrosis Factor-alpha; Weight Gain; Xanthophylls