Ligularia fischeri extract attenuates liver damage induced by chronic alcohol intake

Pharm Biol. 2016 Aug;54(8):1465-73. doi: 10.3109/13880209.2015.1104701. Epub 2016 Jan 22.

Abstract

Context Ligularia fischeri (Ledebour) Turcz. (Compositae) has been used as a leafy vegetable and in traditional medicine to treat hepatic disorder in East Asia. Objective The present study explores the antioxidant activity of LF aqueous extract on EtOH-induced oxidative stress accompanied by hepatotoxicity both in vitro and in vivo. Materials and methods In vitro study using the mouse liver NCTC-1469 cell line was conducted to estimate the cytotoxicity as well as the inhibitory effect of LF extract against alcohol-treated cell damage. In vivo study used an alcohol-fed Wister rat model orally administered EtOH (3.95 g/kg of body weight/d) with or without LF extract (100 or 200 mg/kg body weight) for 6 weeks. Serum and liver tissue were collected to evaluate hepatic injury and antioxidant-related enzyme activity. Results The EC50 value for the DPPH radical scavenging capacity of LF extract was 451.5 μg/mL, whereas the IC50 value of LF extract in terms of EtOH-induced reactive oxygen species (ROS) generation was 98.3 μg/mL without cell cytotoxicity. LF extract (200 mg/kg body weight) significantly reduced the triglyceride content of serum (33%) as well as hepatic lipid peroxidation (36%), whereas SOD activity was elevated three-fold. LF extract suppressed expression of CYP2E1 and TNF-α, and attenuated alcohol-induced abnormal morphological changes. Discussion and conclusion LF extract attenuated liver damage induced by alcoholic oxidative stress through inhibition of ROS generation, down-regulation of CYP2E1, and activation of hepatic antioxidative enzymes. Homeostasis of the antioxidative defence system in the liver by LF extract mitigated hepatic disorder following chronic alcohol intake.

Keywords: Alcohol-fed rat model; alcoholic liver disease; antioxidative enzyme; hepatoprotection; reactive oxygen species.

MeSH terms

  • Animals
  • Antioxidants / isolation & purification
  • Antioxidants / pharmacology*
  • Asteraceae / chemistry
  • Biphenyl Compounds / chemistry
  • Cell Line
  • Cytochrome P-450 CYP2E1 / metabolism
  • Cytoprotection
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Lipid Peroxidation / drug effects
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / pathology
  • Liver Diseases, Alcoholic / metabolism
  • Liver Diseases, Alcoholic / pathology
  • Liver Diseases, Alcoholic / prevention & control*
  • Male
  • Mice
  • Oxidative Stress / drug effects*
  • Phytotherapy
  • Picrates / chemistry
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Plant Leaves
  • Plants, Medicinal
  • Rats, Wistar
  • Reactive Oxygen Species / metabolism
  • Superoxide Dismutase / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Antioxidants
  • Biphenyl Compounds
  • Picrates
  • Plant Extracts
  • Reactive Oxygen Species
  • Tumor Necrosis Factor-alpha
  • 1,1-diphenyl-2-picrylhydrazyl
  • Cytochrome P-450 CYP2E1
  • Superoxide Dismutase