Honokiol protects hepatocytes from oxidative injury through mitochondrial deacetylase SIRT3

Eur J Pharmacol. 2018 Sep 5;834:176-187. doi: 10.1016/j.ejphar.2018.07.036. Epub 2018 Jul 20.

Abstract

Oxidative stress contributes to the initiation and progression of liver damage. SIRT3 is a member of nicotinamide adenine dinucleotide-dependent deacetylases that plays a key role in anti-oxidative defense and mitochondrial function in the liver. Honokiol is a natural lignan from the plants of Magnolia genus that exhibits potent anti-oxidative property. This study aims to evaluate the hepatoprotective potential of honokiol against oxidative injury in tert-butyl hydroperoxide (t-BHP)-injured AML12 hepatocytes in vitro and carbon tetrachloride (CCl4)-stimulated liver damaged mice in vivo and to determine whether or not this effect occurs by activating SIRT3. The results showed honokiol protects t-BHP-injured AML12 hepatocytes and CCl4-stimulated liver damage in mice by activating SIRT3. Honokiol reduces the acetylation level of superoxide dismutase 2 to enhance its anti-oxidative capacity, which decreases reactive oxygen species accumulation in AML12 cells. Honokiol increases the deacetylated peroxisome proliferator-activated receptor γ coactivator 1-α level to promote mitochondrial biogenesis. Moreover, honokiol attenuates t-BHP induced mitochondrial fragmentation through Ku70-dynamin-related protein 1 axis. These results suggest that honokiol can ameliorate oxidative damage in hepatocytes by activating SIRT3, which might be a potential therapeutic agent for liver oxidative injury.

Keywords: Fragmentation; Honokiol; Liver; Mitochondria; Oxidative stress; SIRT3.

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Animals
  • Biphenyl Compounds / pharmacology*
  • Cell Line
  • Cytoprotection / drug effects*
  • Enzyme Activation / drug effects
  • Hepatocytes / cytology
  • Hepatocytes / drug effects*
  • Hepatocytes / metabolism
  • Lignans / pharmacology*
  • Mice
  • Mitochondria / drug effects*
  • Mitochondria / enzymology*
  • Oxidative Stress / drug effects*
  • Protein-Serine-Threonine Kinases / metabolism
  • Signal Transduction / drug effects
  • Sirtuin 3 / metabolism*

Substances

  • Biphenyl Compounds
  • Lignans
  • Sirt3 protein, mouse
  • honokiol
  • Stk11 protein, mouse
  • Protein-Serine-Threonine Kinases
  • AMP-Activated Protein Kinases
  • Sirtuin 3