ZFIN ID: ZDB-PUB-200403-9
Rosmarinic acid protects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced dopaminergic neurotoxicity in zebrafish embryos
Zhao, Y., Han, Y., Wang, Z., Chen, T., Qian, H., He, J., Li, J., Han, B., Wang, T.
Date: 2020
Source: Toxicology in vitro : an international journal published in association with BIBRA   65: 104823 (Journal)
Registered Authors: He, Jie
Keywords: Antioxidant, Neurotoxicity, Rosmarinic acid, Zebrafish embryos
MeSH Terms:
  • Animals
  • Cinnamates/pharmacology*
  • Depsides/pharmacology*
  • Dopaminergic Neurons/drug effects
  • Embryo, Nonmammalian
  • Glutathione/metabolism
  • Locomotion/drug effects
  • MPTP Poisoning/drug therapy*
  • MPTP Poisoning/metabolism
  • MPTP Poisoning/physiopathology
  • Malondialdehyde/metabolism
  • Neuroprotective Agents/pharmacology*
  • Reactive Oxygen Species/metabolism
  • Zebrafish
PubMed: 32147576 Full text @ Toxicol. In Vitro
Rosmarinic acid (RA) is an extract that can be obtained from Lamiaceae herbs and the Boraginaceae family. This study aimed to evaluate the effect of RA on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurotoxicity in zebrafish embryos. Embryos were challenged with MPTP and then were treated with RA or brusatol (a Nrf2 inhibitor). Locomotor activity of zebrafish was recorded using a video camera. The swimming distance was analyzed with SMART 3.0 software. Tyrosine hydroxylase (TH) immunohistochemistry, reactive oxygen species (ROS), glutathione (GSH), and malondialdehyde (MDA) contents were evaluated. The expressions of proteins in the DJ-1/Akt/Nrf2 signaling pathway were measured. The results showed that RA not only prevented MPTP-induced dopaminergic neuron loss, but also attenuated the deficit in locomotor behavior. RA attenuated the increases of ROS and MDA induced by MPTP. Treatment with RA augmented expression of glutamate cysteine ligase catalytic subunit, glutamate cysteine ligase modifier subunit, and GSH. Furthermore, RA increased the expression of DJ-1, p-Akt, Nuclear-Nrf2, HO-1 and inhibited the expression of PTEN. Brusatol partially abolished the neuroprotective effect of RA in MPTP-induced Parkinson's disease (PD) model of zebrafish embryos. The results of this study indicate that RA exerts neuroprotective effects on MPTP-induced neurotoxicity in dopaminergic neurons of a zebrafish PD model. The mechanism underlying the effects of RA is associated with promotion of antioxidant gene expression via regulation of the DJ-1/Akt/Nrf2 signaling pathway.