Xanthotoxin reverses Parkinson's disease-like symptoms in zebrafish larvae and mice models: a comparative study

Pharmacol Rep. 2021 Feb;73(1):122-129. doi: 10.1007/s43440-020-00136-9. Epub 2020 Jul 22.

Abstract

Background: The aim of this study is to preliminary evaluate the antiparkinsonian activity of furanocoumarin-xanthotoxin, in two behavioral animal models, zebrafish larvae treated with 6-hydroxydopamine and mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in order to compare both models.

Methods: Xanthotoxin was isolated from Pastinaca sativa L. (Apiaceae) fruits. Then, the compound was administered by immersion to zebrafish 5 days after fertilization (dpf) larvae or intraperitoneally to male Swiss mice, as a potential therapeutic agent against locomotor impairments.

Results: Acute xanthotoxin administration at the concentration of 7.5 µM reversed locomotor activity impairments in 5-dpf zebrafish larvae. In mice model, acute xanthotoxin administration alleviated movement impairments at the concentration of 25 mg/kg.

Conclusions: The similar activity of the same substance in two different animal models indicates their compatibility and proves the potential of in vivo bioassays based on zebrafish models. Results of our study indicate that xanthotoxin may be considered as a potential lead compound in the discovery of antiparkinsonian drugs.

Keywords: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; 6-Hydroxydopamine; Coumarin; Mice; Parkinson’s disease; Zebrafish.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antiparkinson Agents / therapeutic use*
  • Biological Assay
  • Drug Discovery
  • Fruit / chemistry
  • Larva
  • MPTP Poisoning / drug therapy
  • Male
  • Methoxsalen / therapeutic use*
  • Mice
  • Movement Disorders / drug therapy
  • Oxidopamine
  • Parkinson Disease, Secondary / chemically induced*
  • Parkinson Disease, Secondary / drug therapy*
  • Pastinaca / chemistry
  • Plant Extracts / therapeutic use
  • Species Specificity
  • Zebrafish*

Substances

  • Antiparkinson Agents
  • Plant Extracts
  • Oxidopamine
  • Methoxsalen