Inhibition of NLRP3 inflammasome: a new protective mechanism of cinnamaldehyde in endotoxin poisoning of mice

Abstract

Context: Cinnamaldehyde (CA) has a protective effect in endotoxin poisoning of mice, but there is no direct evidence for the protective effect of CA through inhibition of NLRP3 inflammasome activation in endotoxin poisoning of mice.Objective: We aimed to investigate the protective mechanism of CA in endotoxin poisoned mice through NLRP3 inflammasome.Materials and methods: First, we evaluated the anti-inflammatory effect of CA in phorbol-12-myristate acetate–differentiated THP-1 cells through the NLRP3 inflammasome. Second, in a mouse model of lipopolysaccharide (LPS)-induced endotoxin poisoning, CA was administrated for 5 d (once a day) before the 15 mg/kg LPS challenge. Then, the levels of IL-1β in serum were measured, and the effect of CA on the NLRP3 inflammasome activation and the expression of cathepsin B and P2X7R proteins in lung were explored.Results: In vitro, CA decreased the levels of p20, pro-IL-1β and IL-1β in cell culture supernatants, as well as the expression of NLRP3 and IL-1β mRNA in cells. In vivo, CA decreased IL-1β production in serum. Furthermore, CA suppressed LPS-induced NLRP3, p20, Pro-IL-1β, P2X7 receptor (P2X7R) and cathepsin B protein expression in lung, as well as the expression of NLRP3 and IL-1β mRNA.Conclusions: CA has a protective effect in the endotoxin poisoned mice through the inhibition of NLRP3 inflammasome activation. Furthermore, CA suppresses the NLRP3 inflammasome activation by inhibiting the expression of cathepsin B and P2X7R protein expression. CA can be considered as a potential therapeutic candidate for diseases involved in endotoxin poisoning such as sepsis.