In vivo efficacy study of milk thistle extract (ETHIS-094™) in STAM™ model of nonalcoholic steatohepatitis

Drugs R D. 2014 Dec;14(4):291-9. doi: 10.1007/s40268-014-0068-2.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine Transaminase / blood
  • Animals
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Liver / drug effects
  • Liver / pathology
  • Male
  • Mice
  • Non-alcoholic Fatty Liver Disease / blood
  • Non-alcoholic Fatty Liver Disease / chemically induced
  • Non-alcoholic Fatty Liver Disease / drug therapy*
  • Non-alcoholic Fatty Liver Disease / pathology
  • Organ Size / drug effects
  • Phytotherapy
  • Plant Extracts / pharmacology*
  • Plant Extracts / therapeutic use*
  • Seeds / chemistry
  • Silybum marianum / chemistry
  • Streptozocin

Substances

  • Plant Extracts
  • Streptozocin
  • Alanine Transaminase