炎症体
咖啡因
MAPK/ERK通路
TLR4型
药理学
化学
信号转导
肝损伤
蛋白激酶A
氧化应激
p38丝裂原活化蛋白激酶
内分泌学
受体
内科学
磷酸化
医学
生物化学
作者
Eduardo E. Vargas-Pozada,Erika Ramos‐Tovar,Juan D. Rodríguez-Callejas,Irina Cardoso-Lezama,Silvia Galindo‐Gómez,Daniel Talamás‐Lara,Verónica Rocío Vásquez-Garzón,Jaime Arellanes‐Robledo,Vı́ctor Tsutsumi,Saúl Villa‐Treviño,Pablo Muriel
摘要
Caffeine elicits protective effects against liver diseases, such as NASH; however, its mechanism of action involving the pyrin domain-containing-3 (NLRP3) inflammasome signaling pathway remains to be elucidated. This study aimed to evaluate the effect of caffeine on the NLRP3 inflammasome signaling pathway in a rat model of NASH. NASH was induced by feeding rats a high-fat, -sucrose, and -cholesterol diet (HFSCD) for 15 weeks along with a weekly low dose (400 mg/kg, i.p.) of CCl4. Caffeine was administered at 50 mg/kg p.o. The effects of HFSCD+CCl4 and caffeine on the liver were evaluated using biochemical, ultrastructural, histological, and molecular biological approaches. The HFSCD+CCl4-treated rats showed fat accumulation in the liver, elevated levels of inflammatory mediators, NLRP3 inflammasome activation, antioxidant dysregulation, and liver fibrosis. Caffeine reduced necrosis, cholestasis, oxidative stress, and fibrosis. Caffeine exhibited anti-inflammatory effects by attenuating NLRP3 inflammasome activation. Moreover, caffeine prevented increases in toll-like receptor 4 (TLR4) and nuclear factor-κB (NF-κB) protein levels and mitigated the phosphorylation of mitogen-activated protein kinase (MAPK). Importantly, caffeine prevented the activation of hepatic stellate cells. This study is the first to report that caffeine ameliorates NASH by inhibiting NLRP3 inflammasome activation through the suppression of the TLR4/MAPK/NF-κB signaling pathway.
科研通智能强力驱动
Strongly Powered by AbleSci AI