Triterpenic acids-enriched fraction from Cyclocarya paliurus attenuates non-alcoholic fatty liver disease via improving oxidative stress and mitochondrial dysfunction

Biomed Pharmacother. 2018 Aug:104:229-239. doi: 10.1016/j.biopha.2018.03.170. Epub 2018 May 25.

Abstract

The effects of triterpenic acids-enriched fraction from Cyclocarya paliurus (CPT) on nonalcoholic fatty liver disease (NAFLD) were investigated using in vivo and in vitro models. In high fat diet-induced Wister rats, CPT significantly increased superoxide dismutase (SOD) activity and glutathione/oxidized glutathione (GSH/GSSG) ratio, reduced malondialdehyde (MDA) and protein carbonyl (PCO) levels. Moreover, CPT restored mitochondrial membrane potential dysfunction, decreased cytochrome P450 enzyme 2E1 (CYP2E1) activity, improved nuclear factor erythroid 2-related factor 2 (Nrf2) and Nrf2-mediated antioxidant enzyme heme oxygenase1 (HO-1) expression. In free fatty acids-induced HepG2 cells, CPT dramatically decreased ROS content, increased mitochondrial NADH dehydrogenase (Complex I) and mitochondrial cytochrome C oxidase (Complex IV) levels. Furthermore, CPT could upregulate HO-1, quinine oxidoreductase 1 (NQO1) expression, and increase Nrf2 translocation from cytoplasm-to-nucleus. The results indicated CPT could protect mitochondria function and improve oxidative stress by activating Nrf2. Therefore, it can be inferred that CPT may be a potential agent against NAFLD.

Keywords: Cyclocarya paliurus triterpenic acids; Mitochondrial dysfunction; Nonalcoholic fatty liver disease; Oxidative stress.

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Cell Line, Tumor
  • Electron Transport Complex IV / metabolism
  • Glutathione / metabolism
  • Glutathione Disulfide / metabolism
  • Heme Oxygenase-1 / metabolism
  • Hep G2 Cells
  • Humans
  • Juglandaceae / chemistry*
  • Male
  • Malondialdehyde / metabolism
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Mitochondrial Diseases / drug therapy*
  • Mitochondrial Diseases / metabolism
  • NAD(P)H Dehydrogenase (Quinone) / metabolism
  • NADH Dehydrogenase / metabolism
  • NF-E2-Related Factor 2 / metabolism
  • Non-alcoholic Fatty Liver Disease / drug therapy*
  • Non-alcoholic Fatty Liver Disease / metabolism
  • Oxidative Stress / drug effects*
  • Rats
  • Rats, Wistar
  • Superoxide Dismutase / metabolism
  • Triterpenes / pharmacology*

Substances

  • Antioxidants
  • NF-E2-Related Factor 2
  • Triterpenes
  • Malondialdehyde
  • Heme Oxygenase-1
  • Superoxide Dismutase
  • NAD(P)H Dehydrogenase (Quinone)
  • NADH Dehydrogenase
  • Electron Transport Complex IV
  • Glutathione
  • Glutathione Disulfide