Antioxidant and Antiapoptotic Polyphenols from Green Tea Extract Ameliorate CCl4-Induced Acute Liver Injury in Mice

Chin J Integr Med. 2020 Oct;26(10):736-744. doi: 10.1007/s11655-019-3043-5. Epub 2019 Nov 25.

Abstract

Objective: To investigate the phenolic composition, antioxidant properties, and hepatoprotective mechanisms of polyphenols from green tea extract (GTP) in carbon tetrachloride (CCl4)-induced acute liver injury mouse model.

Methods: High-performance liquid chromatography was used to analyze the chemical composition of the extract. Antioxidant activity of GTP was assessed by O2∙-, OH, DPPH, and ferric-reducing antioxidant power (FRAP) assay in vitro. Sixty Kunming mice were divided into 6 groups including control, model, low-, medium-, and high-doses GTP (200, 400, 800 mg/kg) and vitamin E (250 mg/kg) groups, 10 in each group. GTP and vitamin E were administered at a level of abovementioned doses twice per day for 7 days prior to exposure to a single injection of CCl4. Hepatoprotective effects of GTP were evaluated in a CCl4-induced mouse model of acute liver injury, using commercial enzyme linked immunosorbent assay kits, histopathological observation, terminal deoxynucleotidyl transferase-mediated dUTPNick-end labeling (TUNEL) assay and Western blot.

Results: GTP contained 98.56 µg gallic acid equivalents per milligram extract total polyphenols, including epicatechingallate, epigallocatechin gallate, epicatechin, and epigallocatechin. Compared with the model group, low-, medium-, or high doses GTP significantly decreased serum levels of alanine aminotransferase and aspartate transaminase (P<0.01). Histopathological observation confirmed that pretreatment of GTP prevented swelling and necrosis in CCl4-exposed hepatocytes. Hepatoprotective effects of low-, medium-, and high-dose GTP were associated with eliminating free radicals and improving superoxide dismutase, catalase, and glutathione peroxidase activity in the liver. Additionally, low-, medium-, and high-dose GTP decreased cell apoptosis in the CCl4-exposed liver (P<0.01). Phosphorylated nuclear factor kappa-B (NF-κB), p53, Bcl-2 associated x protein/B-cell lymphoma/leukemia-2 gene, cytochrome C, and cleaved caspase-3 levels were downregulated compared with the model group (P<0.01).

Conclusion: GTP achieves hepatoprotective effects by improving hepatic antioxidant status and preventing cell apoptosis through caspase-3-dependent signaling pathways.

Keywords: acute liver injury; anti-apoptosis; anti-oxidant; carbon tetrachloride; green tea; polyphenol.

MeSH terms

  • Animals
  • Antioxidants / chemistry
  • Antioxidants / pharmacology*
  • Apoptosis / drug effects*
  • Biomarkers / blood
  • Carbon Tetrachloride / toxicity
  • Caspase 3 / metabolism
  • Chemical and Drug Induced Liver Injury / drug therapy*
  • China
  • Disease Models, Animal
  • Male
  • Mice
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Polyphenols / chemistry
  • Polyphenols / pharmacology*
  • Tea*

Substances

  • Antioxidants
  • Biomarkers
  • Plant Extracts
  • Polyphenols
  • Tea
  • Carbon Tetrachloride
  • Casp3 protein, mouse
  • Caspase 3