title: Morin, a Bioflavonoid Suppresses Monosodium Urate Crystal-Induced Inflammatory Immune Response in RAW 264.7 Macrophages through the Inhibition of Inflammatory Mediators, Intracellular ROS Levels and NF-κB Activation.
abstract: Our previous studies had reported that morin, a bioflavanoid exhibited potent anti-inflammatory effect against adjuvant-induced arthritic rats. In this current study, we investigated the anti-inflammatory mechanism of morin against monosodium urate crystal (MSU)-induced inflammation in RAW 264.7 macrophage cells, an in vitro model for acute gouty arthritis. For comparison purpose, colchicine was used as a reference drug. We have observed that morin (100-300 μM) treatment significantly suppressed the levels of inflammatory cytokines (TNF-α, IL-1β, IL-6, MCP-1 and VEGF), inflammatory mediators (NO and PEG2), and lysosomal enzymes (acid phosphatase, β-galactosidase, N-acetyl glucosamindase and cathepsin D) in MSU-crystals stimulated macrophage cells. The mRNA expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, and MCP-1), inflammatory enzymes (iNOS and COX-2), and NF-κBp65 was found downregulated in MSU crystal stimulated macrophage cells by morin treatment, however, the mRNA expression of hypoxanthine phospho ribosyl transferse (HPRT) was found to be increased. The flow cytometry analysis revealed that morin treatment decreased intracellular reactive oxygen species levels in MSU crystal stimulated macrophage cells. The western blot analysis clearly showed that morin mainly exerts its anti-inflammatory effects by inhibiting the MSU crystal-induced COX-2 and TNF-α protein expression through the inactivation of NF-κB signaling pathway in RAW 264.7 macrophage cells similar to that of BAY 11-7082 (IκB kinase inhibitor). Our results collectively suggest that morin can be a potential therapeutic agent for inflammatory disorders like acute gouty arthritis.
authors.affiliation: Immunopathology Lab, School of Biosciences and Technology, VIT University, Vellore-632014, Tamil Nadu, India.
authors.forename: Chitra
authors.initials: C
authors.lastname: Dhanasekar
authors.affiliation: Immunopathology Lab, School of Biosciences and Technology, VIT University, Vellore-632014, Tamil Nadu, India.
authors.forename: Sowmiya
authors.initials: S
authors.lastname: Kalaiselvan
authors.affiliation: Immunopathology Lab, School of Biosciences and Technology, VIT University, Vellore-632014, Tamil Nadu, India.
authors.forename: Mahaboobkhan
authors.initials: M
authors.lastname: Rasool
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015210:Arthritis, Gouty / Q000188:drug therapy / Q000473:pathology; D002460:Cell Line; D018932:Chemokine CCL2 / Q000378:metabolism; D003078:Colchicine / Q000494:pharmacology; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D005419:Flavonoids / Q000494:pharmacology*; D006074:Gout Suppressants / Q000494:pharmacology; D007041:Hypoxanthine Phosphoribosyltransferase / Q000096:biosynthesis; D007249:Inflammation / Q000276:immunology / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors*; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D011092:Polyethylene Glycols / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D051996:Transcription Factor RelA / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000378:metabolism; D014527:Uric Acid / Q000009:adverse effects*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis; D047309:Flavones
chemical_list: D000893:Anti-Inflammatory Agents; D018932:Chemokine CCL2; D003078:Colchicine; D051546:Cyclooxygenase 2; D005419:Flavonoids; D006074:Gout Suppressants; D007041:Hypoxanthine Phosphoribosyltransferase; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D011092:Polyethylene Glycols; D017382:Reactive Oxygen Species; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D014527:Uric Acid; D042461:Vascular Endothelial Growth Factor A; C491768:Ccl2 protein, mouse; C587672:IL1B protein, mouse; C498144:Rela protein, mouse; C467480:vascular endothelial growth factor A, mouse; C008548:morin; D047309:Flavones; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse