Silibinin Capsules improves high fat diet-induced nonalcoholic fatty liver disease in hamsters through modifying hepatic de novo lipogenesis and fatty acid oxidation

J Ethnopharmacol. 2017 Aug 17:208:24-35. doi: 10.1016/j.jep.2017.06.030. Epub 2017 Jun 23.

Abstract

Ethnopharmacological relevance: Silibinin Capsules (SC) is a silybin-phospholipid complex with silybin as the bioactive component. Silybin accounts for 50-70% of the seed extract of Silybum marianum (L.) Gaertn.. As a traditional medicine, silybin has been used for treatment of liver diseases and is known to provide a wide range of hepatoprotective effects.

Aim of the study: High fat diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) is a worldwide health problem. This study was to investigate the role of SC in NAFLD with focusing on its underlying mechanism and likely target.

Materials and methods: Male hamsters (Cricetidae) received HFD for 10 weeks to establish NAFLD model. NAFLD was assessed by biochemical assays, histology and immunohistochemistry. Proton nuclear magnetic resonance spectroscopy and western blot were conducted to gain insight into the mechanism.

Results: Hamsters fed HFD for 10 weeks developed fatty liver accompanying with increased triglyceride (TG) accumulation, enhancing de novo lipogenesis, increase in fatty acid (FA) uptake and reducing FA oxidation and TG lipolysis, as well as a decrease in the expression of phospho-adenosine monophosphate activated protein kinase α (p-AMPKα) and Sirt 1. SC treatment at 50mg/kg silybin and 100mg/kg silybin for 8 weeks protected hamsters from development of fatty liver, reducing de novo lipogenesis and increasing FA oxidation and p-AMPKα expression, while having no effect on FA uptake and TG lipolysis.

Conclusions: SC protected against NAFLD in hamsters by inhibition of de novo lipogenesis and promotion of FA oxidation, which was likely mediated by activation of AMPKα.

Keywords: AMPKα; CPT−1A; NAFLD; PPARγ; Silibinin capsules.

MeSH terms

  • Alanine Transaminase / blood
  • Animals
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use*
  • Aspartate Aminotransferases / blood
  • Capsules
  • Cricetinae
  • Diet, High-Fat
  • Fatty Acids / metabolism*
  • Insulin / blood
  • Lipogenesis / drug effects*
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Non-alcoholic Fatty Liver Disease / drug therapy*
  • Non-alcoholic Fatty Liver Disease / metabolism
  • Oxidation-Reduction
  • Silybin
  • Silymarin / pharmacology
  • Silymarin / therapeutic use*
  • Triglycerides / metabolism

Substances

  • Antioxidants
  • Capsules
  • Fatty Acids
  • Insulin
  • Silymarin
  • Triglycerides
  • Silybin
  • Aspartate Aminotransferases
  • Alanine Transaminase