The Association of Palmitoylethanolamide with Luteolin Decreases Neuroinflammation and Stimulates Autophagy in Parkinson's Disease Model

CNS Neurol Disord Drug Targets. 2015;14(10):1350-65. doi: 10.2174/1871527314666150821102823.


Parkinson's disease (PD) is a disorder resulted by degeneration of dopaminergic neurons. To counteract the neuroinflammation and oxidative stress of PD, we decided to test a new composite constituted by palmitoylethanolamide (PEA) and luteolin (Lut), in a mass ratio of 10:1, respectively (co-ultraPEALut). In this study the neuroprotective property of the new compound was investigated. For the in vivo model of PD, mice received four injections of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP). Starting 24 h after the first administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), we treated animals with co-ultraPEALut daily until 7 days. On day 8, brains were processed for Western blotting and immunohistochemical analysis. Treatment with co-ultraPEALut reduced the specific markers of PD (tyrosine hydroxylase immunopositive), and the increased levels of activated astrocytes and pro-inflammatory cytokines as well as inducible nitric oxide synthase. Further, the possible association of autophagy with the beneficial effects of coultraPEALut. Western blot analysis and immunofluorescence staining showed that co-ultraPEALut administration increased autophagy process. These data were confirmed by an in vitro model, using SH-SY5Y neuroblastoma cells. Western blot analysis showed that co-ultraPEALut pre-treatment maintained high Beclin-1 and p62 expression, while continued to inhibit the p70S6K expression. Altogether, these results put forward that treatment with co-ultraPEALut is able to modulate both the neuroinflammatory process and the autophagic pathway involved in PD, actions which may underlie its neuroprotective effect.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiparkinson Agents / pharmacology*
  • Astrocytes / drug effects
  • Astrocytes / metabolism
  • Astrocytes / pathology
  • Autophagy / drug effects
  • Autophagy / physiology
  • Brain / drug effects
  • Brain / metabolism
  • Brain / pathology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Dose-Response Relationship, Drug
  • Drug Combinations
  • Drug Evaluation, Preclinical
  • Ethanolamines / pharmacology*
  • Humans
  • Luteolin / pharmacology*
  • MPTP Poisoning / drug therapy*
  • MPTP Poisoning / pathology
  • MPTP Poisoning / physiopathology
  • Male
  • Mice, Inbred C57BL
  • Motor Activity / drug effects
  • Neuroimmunomodulation / drug effects
  • Neuroimmunomodulation / physiology
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurons / pathology
  • Neuroprotective Agents / pharmacology*
  • Random Allocation
  • Treatment Outcome


  • Antiparkinson Agents
  • Drug Combinations
  • Ethanolamines
  • Neuroprotective Agents
  • co-ultraPEALut
  • Luteolin