Euodia daniellii Hemsl. (Bee-Bee Tree) Oil Attenuates Palmitate-Induced Lipid Accumulation and Apoptosis in Hepatocytes

Pharmacology. 2018;101(5-6):298-308. doi: 10.1159/000487892. Epub 2018 Mar 29.

Abstract

Hepatic lipid accumulation and apoptosis is elevated in patients with non-alcoholic steatohepatitis and is closely associated with severity. Saturated fatty acid palmitate stimulates lipid accumulation and apoptosis in hepatocytes. In the present study, we examined bee-bee tree oil (BO)-mediated protective effects on palmitate-induced lipid accumulation and apoptosis in mouse primary hepatocytes. Cells were cultured in a control media or the same media containing 150 or 300 µmol/L of albumin-bound palmitate for 24 h. BO concentrations used were 0, 0.1, 0.2, or 0.5%. Palmitate induced lipid accumulation and mRNA expression of lipogenic genes such as SREBP1c and SCD1. However, BO prevented these changes. Furthermore, palmitate stimulated caspase-3 activity and decreased cell viability in the absence of BO. BO reduced palmitate-induced activation of caspase-3 and cell death in a dose-dependent manner. AMP-activated protein kinase inhibitors abolished the effects of BO. Furthermore, BO suppressed palmitate-induced c-Jun N-terminal kinase (JNK) phosphorylation through the 5' adenosine monophosphate-activated protein kinase (AMPK)-dependent pathway. In conclusion, BO attenuated palmitate-induced hepatic steatosis and apoptosis through AMPK-mediated suppression of JNK signaling. These data suggest that BO is an important determinant of saturated fatty acid-induced lipid accumulation and apoptosis, and may be an effective therapeutic strategy for treatment of obesity-mediated liver diseases.

Keywords: Apoptosis; Euodia daniellii Hemsl.; Hepatic lipid accumulation; Vegetable oil.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Evodia / chemistry*
  • Fatty Liver / prevention & control
  • Hepatocytes / drug effects*
  • Hepatocytes / metabolism
  • Lipid Metabolism / drug effects
  • Mice
  • Palmitic Acid / administration & dosage
  • Plant Oils / administration & dosage
  • Plant Oils / pharmacology*
  • RNA, Messenger / metabolism
  • Stearoyl-CoA Desaturase / genetics
  • Sterol Regulatory Element Binding Protein 1 / genetics

Substances

  • Plant Oils
  • RNA, Messenger
  • Srebf1 protein, mouse
  • Sterol Regulatory Element Binding Protein 1
  • Palmitic Acid
  • Scd1 protein, mouse
  • Stearoyl-CoA Desaturase