Protective Effects of Catechin against Monosodium Urate-Induced Inflammation through the Modulation of NLRP3 Inflammasome Activation

Gouty inflammation results from the stimulation of monosodium urate (MSU). Interleukin-1β (IL-1β) secretion is the primary clinical manifestation of MSU attack, and MSU activates IL-1β through a nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome. This study investigated the protective effect and underlying mechanism of naturally occurring phenolic compounds on MSU-induced inflammation in vivo and in vitro. A screening of phenolic compounds revealed that gallic acid and catechin exhibited the most potent free radical scavenging activities. Subcutaneous injection of gallic acid or catechin significantly reduced MSU-induced IL-1β and IL-6 secretion in C57BL/6 mice. However, only catechin inhibited MSU-induced IL-1β secretion and NLRP3 inflammasome activation in MSU-challenged THP-1 cells. MSU-triggered mitochondrial reactive oxygen species (MtROS) production and intracellular calcium levels were significantly decreased by treatment with catechin in THP-1 cells. Catechin treatment also up-regulated Bcl-2 levels and restored MSU-induced mitochondrial transmembrane potential impairment. These results indicate that the protective effects of catechin on MSU-induced IL-1β secretion are associated with modulation of mitochondrial damage. It also suggests that catechin has the potential to protect gout attack by modulation of NLRP3 inflammasome activation