title: Docosahexaenoic acid ester of phloridzin inhibit lipopolysaccharide-induced inflammation in THP-1 differentiated macrophages.
abstract: Phloridzin or phlorizin (PZ) is a predominant phenolic compound found in apple and also used in various natural health products. Phloridzin shows poor absorption and cellular uptake due to its hydrophilic nature. The aim was to investigate and compare the effect of docosahexaenoic acid (DHA) ester of PZ (PZ-DHA) and its parent compounds (phloridzin and DHA), phloretin (the aglycone of PZ) and cyclooxygenase inhibitory drugs (diclofenac and nimesulide) on production of pro-inflammatory biomarkers in inflammation-induced macrophages by lipopolysaccharide (LPS)-stimulation. Human THP-1 monocytes were seeded in 24-well plates (5×10(5)/well) and treated with phorbol 12-myristate 13-acetate (PMA, 0.1μg/mL) for 48h to induce macrophage differentiation. After 48h, the differentiated macrophages were washed with Hank's buffer and treated with various concentrations of test compounds for 4h, followed by the LPS-stimulation (18h). Pre-exposure of PZ-DHA ester was more effective in reducing tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2) protein levels compared to DHA and nimesulide. However, diclofenac was the most effective in reducing prostaglandin (PGE2) level by depicting a dose-dependent response. However, PZ-DHA ester and DHA were the most effective in inhibiting the activation of nuclear factor-kappa B (NF-κB) among other test compounds. Our results suggest that PZ-DHA ester might possess potential therapeutic activity to treat inflammation related disorders such as type 2 diabetes, asthma, atherosclerosis and inflammatory bowel disease.
authors: Department of Environmental Sciences, Faculty of Agriculture, Dalhousie University, P.O. Box 550, Truro, NS, Canada B2N 5E3.
authors: Satvir
authors: S
authors: Sekhon-Loodu
authors: Department of Environmental Sciences, Faculty of Agriculture, Dalhousie University, P.O. Box 550, Truro, NS, Canada B2N 5E3.
authors: Ziaullah
authors: Department of Environmental Sciences, Faculty of Agriculture, Dalhousie University, P.O. Box 550, Truro, NS, Canada B2N 5E3; Department of Pathology, Faculty of Medicine, Dalhousie University, Halifax, NS, Canada B34 4R2. Electronic address: vrupasinghe@dal.ca.
authors: H P Vasantha
authors: HP
authors: Rupasinghe
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002454:Cell Differentiation; D002460:Cell Line; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D004008:Diclofenac / Q000494:pharmacology; D004281:Docosahexaenoic Acids / Q000138:chemical synthesis / Q000494:pharmacology*; D005638:Fruit; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D027845:Malus; D016328:NF-kappa B / Q000378:metabolism; D010693:Phloretin / Q000494:pharmacology; D010695:Phlorhizin / Q000138:chemical synthesis / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D013449:Sulfonamides; D004008:Diclofenac; D004281:Docosahexaenoic Acids; C059579:methyl docosahexaenoate; D010695:Phlorhizin; D010693:Phloretin; C012655:nimesulide
keywords: COX-2; Cytokines; Docosahexaenoic acid; Inflammation; Phloridzin; TNF-α