1,8-Cineole Ameliorates Steatosis of Pten Liver Specific KO Mice via Akt Inactivation

Int J Mol Sci. 2015 May 27;16(6):12051-63. doi: 10.3390/ijms160612051.


Hepatocyte-specific Phosphatase and tensin homolog (Pten)-knockout (KO) mice exhibit hepatic lesions analogous to non-alcoholic steatohepatitis (NASH). 1,8-cineole is a monoterpene oxide and it has several biological effects including hepatoprotective effects. In this study we revealed that 1,8-cineole ameliorates NASH of Pten KO mice. Pten KO mice were assigned to a control group without any medication or to a 1,8-cineole group injected with 50 mg/kg i.p. twice per week for eight weeks. At eight weeks, livers from each group were processed to measure triglyceride (TG) content, gene expression analysis, western blot analysis, and histological examination including Oil red O staining. 1,8-cineole ameliorated hepatic steatosis in Pten KO mice, revealed by TG content and Oil red O staining. Moreover, 1,8-cineole downregulated collagen 1a1 expression and improved liver fibrosis. Thus, 1,8-cineole has potential as a candidate to treat NASH by inactivating the Akt/PI3-kinase pathway.

Keywords: 1,8-cineole; Akt; LXR alpha; NASH; PTEN.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Collagen Type I / genetics
  • Collagen Type I / metabolism
  • Cyclohexanols / administration & dosage*
  • Cyclohexanols / pharmacology
  • Eucalyptol
  • Fatty Liver / drug therapy*
  • Fatty Liver / genetics
  • Fatty Liver / metabolism
  • Fatty Liver / pathology
  • Gene Expression Regulation / drug effects
  • Injections, Intraperitoneal
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Mice
  • Mice, Knockout
  • Monoterpenes / administration & dosage*
  • Monoterpenes / pharmacology
  • Organ Specificity
  • PTEN Phosphohydrolase / genetics*
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction / drug effects*
  • Triglycerides / metabolism


  • Collagen Type I
  • Cyclohexanols
  • Monoterpenes
  • Triglycerides
  • Proto-Oncogene Proteins c-akt
  • PTEN Phosphohydrolase
  • Pten protein, mouse
  • Eucalyptol