Effect of Pure Total Flavonoids from Citrus on NLRP3 Inflammasome in Mice with Non-alcoholic Steatohepatitis / 中国药学杂志

ABSTRACT

OBJECTIVE: To investigate the effect of pure total flavonoids from Citrus(PTFC) on the NLRP3 inflammasome pathway in mice with high-fat/high-fructose diet induced non-alcoholic steatohepatitis(NASH), and discuss its anti-NASH mechanism. METHODS: Fifty C57BL/6 mice were randomly divided into normal group, model group, PTFC low-dosage group, medium-dosage group and high-dosage group, 10 in each group. A high-fat/high-fructose diet was given for 16 weeks to establish the NASH models, and the PTFC groups were administrated with PTFC at the dosage of 25, 50, 100 mg•kg-1•d-1 from the 5th week, respectively. Histopathologic changes of the liver tissue were observed by HE and oil red O staining; serum CHOL, TG, ALT, AST were detected by biochemical method; the levels of NLRP3, ASC, Casp1 and IL-1β mRNA in the liver tissue were determined by Realtime-PCR; the protein expression of NLRP3 and Casp1 was detected by Western blot. RESULTS: Sixteen weeks administration of high-fat/high-fructose diet induced significantly higher weight, increased NAFLD activity score (NAS) of the liver tissue, higher level of serum CHOL, ALT and AST, lower level of serum TG, increased expression of NLRP3, ASC, Casp1 and IL-1β mRNA in liver, and increased protein expression of Casp1. After PTFC administration, the mice, especially the PTFC high dosage group, exhibited (compared with the model group) marked lower NAS, decreased serum ALT and AST level, increased TG level, impaired NLRP3, ASC, Casp1 and IL-1β mRNA expression, and decreased protein expression of NLRP3 and Casp1. CONCLUSION: The NLRP3 inflammasome pathway may play a key role in the development and progress of NASH in mice, and PTFC prevents the development of NASH through suppressing this pathway.