Protective and therapeutic activity of honokiol in reversing motor deficits and neuronal degeneration in the mouse model of Parkinson's disease

Pharmacol Rep. 2018 Aug;70(4):668-676. doi: 10.1016/j.pharep.2018.01.003. Epub 2018 Jan 12.

Abstract

Background: Parkinson's disease (PD) is a progressive and profound movement disorder resulting from neurodegeneration in the nigrostriatal dopaminergic system, but current treatment neither cures nor stops PD from advancing. Based on the ability to suppress oxidative stress, excitotoxicity, and neuroinflammation, the potential of honokiol as a novel neuroprotective agent for PD treatment was determined.

Methods: The hemi-parkinsonian model was used to investigate the protective and therapeutic effects of honokiol on motor dysfunctions and dopaminergic neurodegeneration in mice, with a single unilateral striatal injection of 6-hydroxydopamine (6-OHDA).

Results: One day after 6-OHDA-induced lesion, the mice exhibited spontaneous ipsilateral turning, motor imbalance, and incoordination which were mild with a single administration of honokiol prior to 6-OHDA injection. Thereafter, honokiol was continually applied daily for 14 days, which ameliorated apomorphine-induced contralateral rotation and reduced the loss of tyrosine hydroxylase-immunoreactive (TH-ir) fibers in the lesioned striatum. In addition, honokiol posttreatment, beginning on day 8 after 6-OHDA lesion, for 14 days efficiently rescued motor deficits and recovered the TH-ir neuronal loss in both the lesioned striatum and the ipsilateral substantia nigra. The 6-OHDA-induced increases in nigrostriatal expression of inducible nitric oxide synthase (iNOS) and decreases in that of nNOS were also reversed by honokiol posttreatment.

Conclusions: These findings revealed that honokiol has both protective and therapeutic effects on motor impairments and dopaminergic progressive damage, at least in part through modulation of NOS signaling, in 6-OHDA-lesioned mice. Honokiol may represent a potential therapeutic candidate for the management of motor symptoms and neurodegeneration in PD.

Keywords: 6-Hydroxydopamine; Apomorphine; Honokiol; Parkinson’s disease; Tyrosine hydroxylase.

MeSH terms

  • Animals
  • Apomorphine / antagonists & inhibitors
  • Biphenyl Compounds / pharmacology*
  • Biphenyl Compounds / therapeutic use
  • Corpus Striatum / metabolism
  • Disease Models, Animal*
  • Lignans / pharmacology*
  • Lignans / therapeutic use
  • Male
  • Mice
  • Microinjections
  • Motor Activity / drug effects*
  • Neuroprotective Agents / pharmacology*
  • Neuroprotective Agents / therapeutic use
  • Nitric Oxide Synthase Type I / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • Oxidopamine / administration & dosage
  • Parkinson Disease, Secondary / drug therapy*
  • Parkinson Disease, Secondary / prevention & control*
  • Postural Balance / drug effects
  • Substantia Nigra / metabolism
  • Tyrosine 3-Monooxygenase / metabolism

Substances

  • Biphenyl Compounds
  • Lignans
  • Neuroprotective Agents
  • honokiol
  • Oxidopamine
  • Nitric Oxide Synthase Type I
  • Nitric Oxide Synthase Type II
  • Nos1 protein, mouse
  • Tyrosine 3-Monooxygenase
  • Apomorphine