In Vivo Efficacy Study of Milk Thistle Extract (ETHIS-094™) in STAM™ Model of Nonalcoholic Steatohepatitis

INTRODUCTION A subcategory of nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH) is characterized by accumulation of fat accompanied by inflammatory infiltration and hepatocellular damage. The active complex of milk thistle is a lipophilic extract from its seeds, comprising three isomers, collectively known as silymarin. Silymarin has demonstrated antioxidant, anti-inflammatory, and antifibrotic properties, and has been extensively studied in the treatment of liver diseases. The majority of published clinical research on silymarin has used Legalon(®) (Rottapharm/Madaus), containing the patented extract of milk thistle ETHIS-094™ (Euromed). The current study was undertaken to examine the effects of ETHIS-094™ in the Stelic Animal Model (STAM™), a validated and widely used animal model for NASH. METHODS After 4 h fasting from 4 to 8 weeks of age, 15 male mice in whom NASH had been induced were orally administered, once daily, either (1) vehicle (saline) at a volume of 10 mL/kg, (2) vehicle supplemented with milk thistle at a dose of 500 mg/kg, or (3) vehicle supplemented with milk thistle at a dose of 1,000 mg/kg. RESULTS Mean liver weight and the liver-to-body weight ratio were significantly (P < 0.01) decreased in the milk thistle high-dose group compared with the vehicle group. NAFLD activity score (NAS) tended to decrease in the milk thistle treatment groups compared with vehicle group, as did steatosis scores. CONCLUSION Milk thistle extract administration induced a decreasing trend in NAS compared with the vehicle group. Milk thistle induced a numerical decrease of the steatosis score compared with vehicle, and this was accompanied by a statistically significant decrease in liver weight and the liver-to-body weight ratio, implying a potential anti-steatosis effect of milk thistle.