Neuroprotective effects of Brazilian green propolis on oxytosis/ferroptosis in mouse hippocampal HT22 cells

Food Chem Toxicol. 2019 Oct:132:110669. doi: 10.1016/j.fct.2019.110669. Epub 2019 Jul 10.

Abstract

Propolis is a sticky dark-colored substance produced by honey bees and comprises resin, balsam, wax, essential and aromatic oils, pollen, and several other substances; it is used in food and beverages to improve health and prevent diseases. We studied the neuroprotective effects of extracts of Brazilian green propolis in the mouse hippocampal cell line HT22. Ethanol extracts of Brazilian green propolis had a more potent preventive effect on oxidative stress-induced cell death, oxytosis/ferroptosis, in HT22 cells than water extracts of Brazilian green propolis, whereas it did not protect against anticancer drug-induced apoptotic cell death. Among the primary constituents of ethanol extracts of Brazilian green propolis, only artepillin C, kaempferide, and kaempferol demonstrated neuroprotective effects against oxytosis/ferroptosis. The flavonoid derivatives kaempferide and kaempferol are antioxidants with radical-scavenging abilities that additionally induce antioxidant response element-mediated transcriptional activity, suggesting that upregulation of endogenous antioxidant defense protects against oxidative stress. In contrast, artepillin C attenuated reactive oxygen species production; however, it did not induce antioxidant response element activation. These findings indicate that the ethanol extracts of Brazilian green propolis help to prevent oxidative stress-related neuronal cell death that is involved in the pathogenesis of several neurodegenerative diseases.

Keywords: Antioxidant response element; Artepillin C; Brazilian green propolis; Kaempferide; Neuroprotective effect; Oxytosis/Ferroptosis.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Brazil
  • Calcium / metabolism
  • Cell Line
  • Glutamic Acid / metabolism
  • Glutathione / metabolism
  • Heme Oxygenase-1 / metabolism
  • Hippocampus / cytology
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Kaempferols / pharmacology
  • Mice
  • Neuroprotective Agents / pharmacology*
  • Oxidative Stress / drug effects*
  • Phenylpropionates / pharmacology
  • Propolis / chemistry
  • Propolis / pharmacology*
  • Reactive Oxygen Species / metabolism
  • Superoxides / metabolism

Substances

  • Kaempferols
  • Neuroprotective Agents
  • Phenylpropionates
  • Reactive Oxygen Species
  • Superoxides
  • Glutamic Acid
  • kaempferide
  • artepillin C
  • kaempferol
  • Propolis
  • Heme Oxygenase-1
  • Glutathione
  • Calcium