Safranal exerts a neuroprotective effect on Parkinson's disease with suppression of NLRP3 inflammation activation

Mol Biol Rep. 2024 Apr 29;51(1):593. doi: 10.1007/s11033-024-09537-y.

Abstract

Background: Parkinson's disease (PD) is a common central nervous system neurodegenerative disease. Neuroinflammation is one of the significant neuropathological hallmarks. As a traditional Chinese medicine, Safranal exerts anti-inflammatory effects in various diseases, however, whether it plays a similar effect on PD is still unclear. The study was to investigate the effects and mechanism of Safranal on PD.

Methods: The PD mouse model was established by 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine MPTP firstly. Next, the degree of muscle stiffness, neuromuscular function, motor retardation and motor coordination ability were examined by observing and testing mouse movement behavior. Immunofluorescence staining was used to observe the expression of tyrosine hydroxylase (TH). The dopamine (DA) content of the striatum was detected by High-performance liquid chromatography (HPLC). The expression of TH and NLRP3 inflammasome-related markers NLRP3, IL-1β, and Capase-1 were detected by Real-time Polymerase Chain Reaction (qRT-PCR) and western blotting (WB) respectively.

Results: Through behavioral testing, Parkinson's mouse showed a higher muscle stiffness and neuromuscular tension, a more motor retardation and activity disorders, together with a worse motor coordination compared with sham group. Simultaneously, DA content and TH expression in the striatum were decreased. However, after using Safranal treatment, the above pathological symptoms of Parkinson's mouse all improved compared with Safranal untreated group, the DA content and TH expression were also increased to varying degrees. Surprisingly, it observed a suppression of NLRP3 inflammation in the striatum of Parkinson's mouse.

Conclusions: Safranal played a neuroprotective effect on the Parkinson's disease and its mechanism was related to the inhibition of NLRP3 inflammasome activation.

Keywords: NLRP3; Neuroprotective; Parkinson’s disease; Safranal.

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Animals
  • Caspase 1 / metabolism
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism
  • Corpus Striatum / pathology
  • Cyclohexenes* / pharmacology
  • Disease Models, Animal*
  • Dopamine / metabolism
  • Inflammasomes* / drug effects
  • Inflammasomes* / metabolism
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Interleukin-1beta / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • NLR Family, Pyrin Domain-Containing 3 Protein* / metabolism
  • Neuroprotective Agents* / pharmacology
  • Neuroprotective Agents* / therapeutic use
  • Parkinson Disease* / drug therapy
  • Parkinson Disease* / metabolism
  • Terpenes* / pharmacology
  • Tyrosine 3-Monooxygenase / metabolism

Substances

  • NLR Family, Pyrin Domain-Containing 3 Protein
  • safranal
  • Neuroprotective Agents
  • Terpenes
  • Nlrp3 protein, mouse
  • Cyclohexenes
  • Inflammasomes
  • Dopamine
  • Interleukin-1beta
  • Tyrosine 3-Monooxygenase
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Caspase 1