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Arazyme, a metalloprotease from the spider Nephila clavata , exerts hepatoprotective activity in CCL 4 -induced acute hepatic injury. This study investigated the hepatoprotective effects in high-fat diet (HFD)-induced non-alcoholic fatty liver disease-like C57BL/6J mice. The mice were randomly divided into four groups ( n = 10/group): the normal diet group, the HFD group, the arazyme group (HFD with 0.025% arazyme), and the milk thistle (MT) group (HFD with 0.1% MT). Dietary supplementation of arazyme for 13 weeks significantly lowered plasma triglyceride (TG) and non-esterified fatty acid levels. Suppression of HFD-induced hepatic steatosis in the arazyme group was caused by the reduced hepatic TG and total cholesterol (TC) contents. Arazyme supplementation decreased hepatic lipogenesis-related gene expression, sterol regulatory element-binding transcription protein 1 ( Srebf1) , fatty acid synthase ( Fas ), acetyl-CoA carboxylase 1 ( Acc1 ), stearoyl-CoA desaturase-1 ( Scd1 ), Scd2 , glycerol-3-phosphate acyltransferase ( Gpam ), diacylglycerol O -acyltransferase 1 ( Dgat1 ), and Dgat2 . Arazyme directly reduced palmitic acid (PA)-induced TG accumulation in HepG2 cells. Arazyme suppressed macrophage infiltration and tumor necrosis factor α ( Tnfa ), interleukin-1β ( Il1b ), and chemokine-ligand-2 ( Ccl2 ) expression in the liver, and inhibited secretion of TNFα and expression of inflammatory mediators, Tnfa , Il1b , Ccl2 , Ccl3 , Ccl4 , and Ccl5 , in PA-induced RAW264.7 cells. Arazyme effectively protected hepatic steatosis and steatohepatitis by inhibiting SREBP-1-mediated lipid accumulation and macrophage-mediated inflammation.

Arazyme Suppresses Hepatic Steatosis and Steatohepatitis in Diet-Induced Non-Alcoholic Fatty Liver Disease-Like Mouse Model