Antioxidant and hepatoprotective effect of polyphenols from apple pomace extract via apoptosis inhibition and Nrf2 activation in mice

Hum Exp Toxicol. 2016 Dec;35(12):1264-1275. doi: 10.1177/0960327115627689. Epub 2016 Jan 25.


Industrial apple pomace, a biowaste generated during apple processing, is rich in cell wall polysaccharides and phenolics. These biologically active compounds are reported to be highly beneficial from the nutritional and health point of view. In the present study, the total phenolic content in the apple pomace aqueous extract (APE) was estimated and evaluated for its possible antioxidant and hepatoprotective efficacy in carbon tetrachloride (CCl4)-induced liver injury mice model. The aqueous extract exhibited 2,2-diphenyl-2-picrylhydrazyl free radical scavenging activity in vitro. Under in vivo study, mice were treated with APE (200 mg and 400 mg/kg body weight) for 2 weeks prior to the administration of CCl4 (30% v/v). The serum liver injury markers alanine transaminase, aspartate transaminase, and alkaline phosphatase were significantly lowered by APE in a dose-dependent manner. The levels of antioxidant parameters superoxide dismutase (SOD), reduced glutathione (redGSH), and lipid peroxidation were also improved by APE in liver homogenate. Histopathological studies revealed that APE treatment significantly lowered the CCl4-induced necrotic changes in the liver. Furthermore, terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end-labeling assay showed that CCl4-induced apoptosis in the liver was significantly inhibited by APE in a dose-dependent manner. Immunohistochemistry results showed higher expression of nuclear erythroid 2-related factor 2 (Nrf2) in the liver of the APE-treated mice, a key regulator of antioxidative response. In conclusion, the results of the present study revealed the hepatoprotective efficacy of APE by inhibiting CCl4-induced apoptosis, which is due to its antioxidant activity and the ability to induce Nrf2 protein expression.

Keywords: Apple pomace; CCl4; Nrf2; apoptosis; hepatoprotective.

MeSH terms

  • Animals
  • Antioxidants / administration & dosage
  • Antioxidants / therapeutic use*
  • Apoptosis / drug effects*
  • Carbon Tetrachloride / toxicity
  • Chemical and Drug Induced Liver Injury / metabolism
  • Chemical and Drug Induced Liver Injury / pathology
  • Chemical and Drug Induced Liver Injury / prevention & control*
  • Dose-Response Relationship, Drug
  • Fruit / chemistry*
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology
  • Liver Function Tests
  • Male
  • Malus / chemistry*
  • Mice
  • NF-E2-Related Factor 2 / metabolism*
  • Plant Extracts / administration & dosage
  • Plant Extracts / therapeutic use*


  • Antioxidants
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, mouse
  • Plant Extracts
  • Carbon Tetrachloride