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

Abstract

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.

Keywords: NF-κB signaling; curcumin; gouty arthritis; monosodium urate (MSU); pyrin domain-containing protein 1 (NLRP3) inflammasome.