The Protective Effects of Neoastilbin on Monosodium Urate Stimulated THP-1-Derived Macrophages and Gouty Arthritis in Mice through NF-κB and NLRP3 Inflammasome Pathways

Abstract

Gouty arthritis (GA) is a frequent inflammatory disease characterized by pain, swelling, and stiffness of joints. Neoastilbin is a flavonoid isolated from the rhizome of Smilax glabra, which possesses various anti-inflammatory effects. However, the mechanism of neoastilbin in treating GA has not yet been clarified. Thus, this study was to investigate the protective effects of neoastilbin in both monosodium urate (MSU) stimulated THP-1-derived macrophages and the animal model of GA by injecting MSU into the ankle joints of mice. The levels of key inflammatory cytokines in MSU stimulated THP-1-derived macrophages were detected by enzyme-linked immunosorbent assay (ELISA) kits. Protein expressions of nuclear factor kappa B (NF-κB) and NOD-like receptor protein 3 (NLRP3) inflammasome pathways were further detected by Western blotting. In addition, swelling degree of ankle joints, the levels of inflammatory factors, infiltration of inflammatory cells and the expressions of related proteins were determined. Swelling degree and histopathological injury in ankle joints of MSU-injected mice were significantly decreased after being treated with neoastilbin. Moreover, neoastilbin significantly diminished the secretion of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), suppressing the activation of NF-κB and NLRP3 inflammasome pathways in both MSU stimulated THP-1-derived macrophages and the mouse model of GA. In summary, neoastilbin could alleviate GA by inhibiting the NF-κB and NLRP3 inflammasome pathways, which provided some evidence for neoastilbin as a promising therapeutic agent for GA treatment.

Pathogenesis of gout: Exploring more therapeutic target

“…33,34 Moreover, it was demonstrated that IL-6 induced osteoclast formation. 35 Wenjing Xu et al 36 found that reducing IL-6 secretion through drug intervention could alleviate the symptoms of gout flare.…”

Kaempferol suppresses inflammation in mice suffering from both hyperuricemia and gouty arthritis through inhibiting NLRP3 inflammasome and NF-κB pathway

“…We also observed signi cant elevation of serum UA, CRE and BUN levels and reduction of urine UA and CRE levels in model mice. As our data indicated, we successfully induced a model combined hyperuricemia and gouty arthritis in mice by combination of intraperitoneal injection of PO and xanthine and intra-articular injection of MSU crystals [12,13,35,36].…”

“…A horizontal line was drawn at 0.5 cm on the ankle of with a fadeless marker as a uni ed standard for measuring the volume of toes before injection. The toe volume was measured before and 2, 4, 6, 20 and 24 h after model establishment with a toe volume measuring device [12,13]. The obtained data were calculated according to the following formula.…”

“…Hyperuricemia models have been established through the oral administration of a mixture of adenine and potassium oxonate (PO), or through a combination of peritoneal injection of PO and intragastric administration of hypoxanthine [9,11]. Gouty arthritis models, on the other hand, have been successfully established in previous studies by injecting with monosodium urate (MSU) into ankle joints [12,13]. However, given that hyperuricemia and gouty arthritis often occur simultaneously in patients, the development of a combined animal model for these conditions is currently lacking.…”

Role of NLRP3 in the pathogenesis and treatment of gout arthritis

“…Specifically, neoastilbin significantly ameliorated swelling degree and histopathological injury in ankle joints of MSU-induced GA mice. In addition, neoastilbin markedly diminished the secretion of IL-1β, IL-6 and TNF-α and repressed the activation of NF-κB and NLRP3 inflammasome pathways in vivo and vitro ( 84 ). Tetrahydropalmatine (THP), the main active component of Corydalis yanhusuo , exhibits excellent anti-inflammatory and analgesic activities.…”