Benzyl Isothiocyanate Reduces High-Fat/High-Cholesterol/Cholic Acid Diet-Induced Non-Alcoholic Steatohepatitis by Inhibiting the Activation of NLRP3 Inflammasome (P06-084-19)

Abstract

ObjectivesNon-alcoholic steatohepatitis (NASH) is one kind of fatty liver disease, which is associated with obesity. Benzyl isothiocyanate (BITC), an organosulfur compound enriched in cruciferous vegetables, shows anti-inflammatory, antioxidant, and anti-tumor activities. This study examined whether BITC protects against high-fat/high-cholesterol/cholic acid diet-induced NASH and the underlying mechanisms involved. MethodsMale C57BL/6 J mice were randomly assigned into three groups: normal diet (ND), high-fat/high-cholesterol/cholic acid diet (HFCCD), or HFCCD supplemented with 0.1% BITC. After a 9-weeks feeding, liver tissues and blood samples were collected for analysis. ResultsCompared with mice fed with ND, the liver weight and the contents of serum GOP, GPT, and total cholesterol as well as hepatic triglycerides and total cholesterol were significantly increased in mice fed with HFCCD (p < 0.05). HFCCD-induced increases in serum GPT and hepatic triglyceride were significantly decreased by BITC (p < 0.05). Histological examination revealed that macrophage infiltration, fibrosis, and the formation of crown-like structure were induced in mice fed with HFCCD, and these inductions were attenuated by BITC. Increases in the expression of NLRP3 mRNA and protein and caspase 1 and IL-1β mRNA as well as the cleaved caspase 1 (p20) and IL-1β (p17) proteins in the liver as well as serum IL-1β concentration were evidenced in HFCCD-fed mice. In the presence of BITC, HFCCD-induced hepatic NLRP3, caspase 1, and IL-1β expression was mitigated. ConclusionsThese findings suggest that BITC possesses potent anti-steatohepatitis activity, and this protection is likely to be associated with the inhibition of NLRP3 inflammasome activation. Funding SourcesThis study was supported by the Minister of Science and Technology, Taiwan.