Curcumin ameliorates monosodium urate‐induced gouty arthritis through Nod‐like receptor 3 inflammasome mediation via inhibiting nuclear factor‐kappa B signaling

• Published in: Journal of cellular biochemistry 2019-04, Vol.120 (4), p.6718-6728
• Main Authors: Li, Xiong, Xu, Da‐Qi, Sun, De‐Yi, Zhang, Tao, He, Xi, Xiao, Dong‐Min
• Format: Article
• Language: English
• Subjects: Animal models; Arthritis; Caspase; Crystals; Curcumin; Cytokines; Effectiveness; Elastase; gouty arthritis; In vivo methods and tests; Infiltration; Inflammasomes; Inflammation; Interleukins; Joint diseases; Knee; Leukocytes (neutrophilic); Macrophages; Mediation; Metastases; monosodium urate (MSU); NF‐κB signaling; Polymerase chain reaction; pyrin domain–containing protein 1 (NLRP3) inflammasome; Rodents; Signaling; Signs and symptoms; Tumor necrosis factor; Tumor necrosis factor-TNF; Uric acid
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.27969

Background Monosodium urate (MSU) crystals‐induced inflammation is a key initiator in gouty arthritis. Curcumin is an active ingredient possessing anti‐inflammatory efficacy. But the underlying mechanism is not fully understood and its effect on gouty arthritis remains elusive. Methods We evaluated the effects of curcumin on cell viability in primary rat abdominal macrophages with 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT). Then supernatants of MSU crystals–stimulated cells were collected and subjected to enzyme‐linked immunosorbent assay for checking the modulation of curcumin on interleukin (IL)‐1β and tumor necrosis factor (TNF)‐α. Meanwhile, cells were analyzed by using Western blot analysis and quantitative polymerase chain reaction (QPCR) to investigate the effects of curcumin on Nod‐like receptor 3 (NLRP3) inflammasome/nuclear factor‐kappa B (NF‐κB) signaling. We also investigated the in vivo efficacy of curcumin with MSU‐induced gouty arthritis rat models. Results Curcumin could reduce MSU crystals‐induced IL‐1β and TNF‐α in vitro. Western blot analysis and QPCR results revealed that curcumin regulated the production of these cytokines by suppressing the expression of inflammasome key components, including NLRP3, caspase‐1. Further studies showed that the suppressive efficacy of curcumin on inflammasome was mediated by inhibiting MSU‐induced NF‐κB signaling activation. Intraperitoneal administration of curcumin could ameliorate symptoms of MSU‐induced gouty arthritis, including the joint circumference, infiltration of neutrophils in knee joints, and production of IL‐1β, TNF‐α, and elastase. Western blot analysis revealed that the levels of NLRP3, procaspase‐1, caspase‐1, pro‐IL‐1β, and IL‐1β were downregulated by curcumin in vivo. Conclusions These results indicated that curcumin could effectively ameliorate MSU crystal‐induced gouty arthritis through NLRP3 inflammasome mediation via inhibiting NF‐κB signaling both in vitro and in vivo, suggesting a promising active ingredient for the prevention and treatment of gouty arthritis. Curcumin inhibits Monosodium urate (MSU)‐induced inflammation in primary cultured macrophages. Curcumin ameliorates MSU‐induced gouty arthritis in Rattus norvegicus. Curcumin suppresses the activation of the NLRP3 inflammasome. Curcumin inhibits NLRP3 inflammasome via NF‐kB signaling.