Acteoside protects against 6-OHDA-induced dopaminergic neuron damage via Nrf2-ARE signaling pathway

Food Chem Toxicol. 2018 Sep:119:6-13. doi: 10.1016/j.fct.2018.06.018. Epub 2018 Jun 12.

Abstract

Acteoside has been reported to have antioxidant and neuroprotective effect, which is a promising therapeutic way in prevention and treatment of Parkinson's disease. The present study was aimed to understand the neuroprotective effect of acteoside and to elucidate its underlying mechanism. 6-hydroxydopamine (6-OHDA)-induced neural damage in zebrafish model was used to study the protective effect of acteoside on Parkinson's disease (PD). Locomotion behavioral test showed that acteoside could prevent 6-OHDA-stimulated movement disorders. Anti-tyrosine hydroxylase (TH) whole-mount immunostaining analysis showed that acteoside could prevent 6-OHDA-induced dopaminergic neuron death. In addition, pretreatment with acteoside could upregulate antioxidative enzymes by activating the Nrf2/ARE signaling pathway in zebrafish. Meanwhile, acteoside was found to be distributed in the brain after intraperitoneal injection into the adult zebrafish, indicating that this compound could penetrate the blood-brain-barrier (BBB). This study demonstrated that acteoside could penetrate BBB and have potential therapeutic value for PD by activating the Nrf2/ARE signaling pathway and attenuating the oxidative stress.

Keywords: Acteoside; Nrf2; Parkinson's disease; The blood-brain-barrier; Zebrafish.

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Carboxylic Ester Hydrolases / genetics
  • Carboxylic Ester Hydrolases / metabolism*
  • Dopaminergic Neurons / drug effects*
  • Gene Expression Regulation, Enzymologic / drug effects
  • Glucosides / pharmacology*
  • Larva
  • Malondialdehyde / metabolism
  • Metabolic Networks and Pathways / drug effects
  • Motor Activity / drug effects
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism*
  • Oxidopamine / toxicity*
  • Phenols / pharmacology*
  • Zebrafish
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism*

Substances

  • Antioxidants
  • Glucosides
  • NF-E2-Related Factor 2
  • Phenols
  • Zebrafish Proteins
  • nfe2l2a protein, zebrafish
  • acteoside
  • Malondialdehyde
  • Oxidopamine
  • Carboxylic Ester Hydrolases
  • arylesterase