Dihydromyricetin Inhibits Lead-Induced Cognitive Impairments and Inflammation by the Adenosine 5'-Monophosphate-Activated Protein Kinase Pathway in Mice

J Agric Food Chem. 2018 Aug 1;66(30):7975-7982. doi: 10.1021/acs.jafc.8b02433. Epub 2018 Jul 19.


Dihydromyricetin (DHM), a natural flavonoid derived from the medicinal and edible plant Ampelopsis grossedentata, exhibits antioxidant, antiapoptosis, antitumor, and anti-inflammatory bioactivities. This study evaluated the effects of DHM on Pb-induced neurotoxicity and explored the underlying mechanisms. DHM significantly ameliorated behavioral impairments of Pb-induced mice. It decreased the levels of lipid peroxidation and protein carbonyl and increased the activities of superoxide dismutase and catalase in the brains. DHM suppressed Pb-induced apoptosis, as indicated by the decreased levels of Bax and cleaved caspase-3. DHM also decreased inflammatory cytokines in the brains of Pb-treated mice. DHM decreased amyloid-beta (Aβ) level and nuclear factor-κB nuclear translocation. Moreover, DHM induced the adenosine 5'-monophosphate-activated protein kinase (AMPK) phosphorylation and inhibited the activation of p38, Toll-like receptor 4, myeloid differentiation factor 88, and glycogen synthase kinase-3. Collectively, this is the first report indicating that DHM could improve Pb-induced cognitive functional impairment by preventing oxidative stress, apoptosis, and inflammation and that the protective effect was mediated partly through the AMPK pathway.

Keywords: AMPK; apoptosis; dihydromyricetin; inflammation; lead; oxidative stress.

MeSH terms

  • AMP-Activated Protein Kinase Kinases
  • Ampelopsis / chemistry*
  • Animals
  • Apoptosis / drug effects
  • Brain / drug effects
  • Brain / immunology
  • Cognitive Dysfunction / drug therapy*
  • Cognitive Dysfunction / etiology
  • Cognitive Dysfunction / metabolism
  • Cognitive Dysfunction / physiopathology
  • Cytokines / genetics
  • Cytokines / metabolism
  • Flavonols / administration & dosage*
  • Humans
  • Inflammation / drug therapy
  • Inflammation / genetics
  • Inflammation / metabolism
  • Lead / toxicity*
  • Mice
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Phosphorylation / drug effects
  • Plant Extracts / administration & dosage*
  • Protein Kinases / genetics
  • Protein Kinases / metabolism*
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / metabolism


  • Cytokines
  • Flavonols
  • NF-kappa B
  • Plant Extracts
  • Toll-Like Receptor 4
  • Lead
  • Protein Kinases
  • AMP-Activated Protein Kinase Kinases
  • dihydromyricetin