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.

Morin exerts neuroprotection via attenuation of ROS induced oxidative damage and neuroinflammation in experimental diabetic neuropathy

“…Besides to its antioxidant property, morin administration also proved to show anti-inflammatory properties in several animal models [41][42][43]. Emerging evidence have shown that antiinflammatory properties of morin are mediated through attenuation of ROS mediate NF-jB activation and amelioration of mitochondrial dysfunction [21,44,45].…”

Demethylzeylasteral ameliorates inflammation in a rat model of unilateral ureteral obstruction through inhibiting activation of the NF-κB pathway

“…NF-κB can form a tripolymer by combining with inhibitor of NF-κB (IkB). When IkB degrades and is lost, a dipolymer with transcriptional activity is formed (9). The activated dipolymer has the following functions in renal interstitial fibrosis (8): Firstly, it is associated with fibroblast growth factors generated by fibroblasts and intrinsic renal cells.…”

“…As an important factor for the control of genetic transcription, nuclear factor (NF) -κB may be activated by the stimulation of cytokines, protein kinase, viruses and oxidizing agents (8). The activated NF-κB can induce the expressions of cytokines, growth factors and chemotactic factors, and be involved in pathological processes, including inflammatory responses, fibrosis, tumor development and atherosclerosis (9). Activated NF-κB can promote the transcription of monocyte chemoattractant protein-1, the excessive expression of which reduces the infiltration of macrophages and interstitial fibrosis (10,11).…”

IL-17A neutralizing antibody regulates monosodium urate crystal-induced gouty inflammation

“…Gout is characterized by the deposition of MSU crystals in joints, which is associated with the rise of serum urate content, leading to excruciating pain and inflammatory events [50,51]. MSU crystals deposits or tophi further induce chronic inflammatory responses that may lead to joint damage, often referred to as gouty arthritis or chronic gout [52].…”