Analysis of Therapeutic Effects of Paeonol on Candida albicans Aggravated Alcoholic Liver Disease (ALD) through Dectin-1/TLR2/NLRP3 Pathway

Alcoholic liver disease (ALD) is caused by long-term alcohol consumption and is associated with the changes in the composition of intestinal mycobiota, especially Candida albicans. Pharmacological therapy to improve intestinal ecological imbalance is becoming a promising strategy for ALD treatment. An ALD mod-el induced by C. albicans was established in C57BL/6 mice using a well-defined chronic-plus-binge ethanol diet protocol and treated by Paeonol (Pae) at 480 mg/kg. Meanwhile, RAW 264.7 cells were incubated with C. albicans or zymosan in the presence of 250 & mu;g/mL laminarin (Dectin1 inhibitor) and 480 & mu;mol/L Pae. The ex-pressions of several critical proteins and genes of Dectin-1/TLR2/NLRP3 pathway were also examined in both animal and cell experiments. Compared with ALD mice, exogenous C. albicans could significantly promote the progression of ALD with aggravated pathological signs and abnormally activated liver macrophages. The mice treated with Pae could greatly reduce liver fungal capacity, the levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), total cholesterol (T-CHO) content, and hepatic damage. Both in vivo and in vitro, the flamed macrophages were quenched, and the expression of proteins and genes of Dectin-1/TLR2/NLRP3 pathway were inhibited to some extent after Pae treatment compared with the ALD mice with C. albicans or zymosan intervention. Introgastric administration of C. albicans can worsen alcohol-induced liver damage via liver-intestine axis. Whereas Pae can reduce the injuries of ALD with C. albicans intervention, and the potential underlying mechanism might involve the Dectin-1/TLR2/NLRP3 pathway.