Xu Feng, Wang Feng, Wen Taoqun, Sang Wentao, Wang Dejian, Zeng Nan
a College of Pharmacy , Guiyang College of Traditional Chinese Medicine , Guiyang , Guizhou Province , P.R. China.
b Department of Pharmacology, College of Pharmacy , Chengdu University of Traditional Chinese Medicine , Chengdu , Sichuan , P.R. China.
Immunopharmacol Immunotoxicol. 2017 Oct;39(5):296-304. doi: 10.1080/08923973.2017.1355377. Epub 2017 Aug 1.
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.
We aimed to investigate the protective mechanism of CA in endotoxin poisoned mice through NLRP3 inflammasome.
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.
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.
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.
肉桂醛（CA）对小鼠内毒素中毒具有保护作用，但尚无直接证据表明CA通过抑制小鼠内毒素中毒时NLRP3炎性小体激活发挥保护作用。
旨在研究CA通过NLRP3炎性小体对小鼠内毒素中毒的保护机制。
首先，通过NLRP3炎性小体评估CA在佛波酯-12-肉豆蔻酸酯-13-乙酸酯分化的THP-1细胞中的抗炎作用。其次，在脂多糖（LPS）诱导的内毒素中毒小鼠模型中，于15 mg/kg LPS攻击前连续5天（每天1次）给予CA。然后，检测血清中IL-1β水平，探讨CA对肺组织中NLRP3炎性小体激活以及组织蛋白酶B和P2X7R蛋白表达的影响。
体外实验中，CA降低了细胞培养上清液中p20、前体IL-1β和IL-1β水平，以及细胞中NLRP3和IL-1β mRNA表达。体内实验中，CA降低了血清中IL-1β的产生。此外，CA抑制了LPS诱导的肺组织中NLRP3、p20、前体IL-1β、P2X7受体（P2X7R）和组织蛋白酶B蛋白表达，以及NLRP3和IL-1β mRNA表达。
CA通过抑制NLRP3炎性小体激活对小鼠内毒素中毒具有保护作用。此外，CA通过抑制组织蛋白酶B和P2X7R蛋白表达来抑制NLRP3炎性小体激活。CA可被视为脓毒症等内毒素中毒相关疾病的潜在治疗候选药物。
