Safranal-promoted differentiation and survival of dopaminergic neurons in an animal model of Parkinson's disease

Pharm Biol. 2018 Dec;56(1):450-454. doi: 10.1080/13880209.2018.1501705.

Abstract

Context: Safranal (SAF) is verified to have potential effects in promoting nerve growth.

Objectives: This study verifies the role of SAF in promoting dopaminergic neurons growth in vitro and in vivo.

Material and methods: Rat neural stem cells (NSC) were treated with 1, 20, or 100 ng/mL of SAF, and the expression levels of tyrosine hydroxylase (TH) and dopamine transporter (DAT) were assayed by flow cytometry and real-time PCR and the secretion of dopamine (DA) was assayed by ELISA. Then, 2 × 106 cells of SAF-treated NSC was administrated into PD rat models induced by 6-OHDA. The differentiation and survival of dopaminergic neurons was identified by fluorescence microscope and TH+ cells by immunostaining and DA secretion by ELISA at week 2 and week 4, respectively.

Results: After being treated with SAF at 20 and 100 ng/mL for 1 week, TH and DAT positive rates increased 1.4- and 1.7-fold (p < 0.01, respectively). TH and DAT mRNA also increased 8.05- and 4.41-fold, respectively. And the release of DA statistically increased 1.5-fold (p < 0.01). In vivo, the number of rotations decreased to 4.33 ± 0.97 rpm (p < 0.01) and the survival rates increased to 77.66 ± 7.87% (p < 0.05) at week 4 after transplantation of SAF-treated NSC. Moreover, the transplanted cells increased three-fold, TH fluorescence density increased four-fold and DA releases increased 1.4-fold (p < 0.01) at week 4 after transplantation.

Conclusions: SAF promoted the production of functional DA cells and alleviated PD, which may contribute to a new therapy for PD patients.

Keywords: Neural stem cell; tyrosine hydroxylase.

MeSH terms

  • Animals
  • Cell Differentiation / drug effects
  • Cyclohexenes / pharmacology*
  • Disease Models, Animal
  • Dopamine / metabolism
  • Dopamine Plasma Membrane Transport Proteins / biosynthesis
  • Dopamine Plasma Membrane Transport Proteins / metabolism
  • Dopaminergic Neurons / drug effects*
  • Dopaminergic Neurons / metabolism
  • Dopaminergic Neurons / pathology*
  • Green Fluorescent Proteins / analysis
  • Green Fluorescent Proteins / biosynthesis
  • Neural Stem Cells / cytology
  • Neural Stem Cells / drug effects*
  • Oxidopamine
  • Parkinsonian Disorders / chemically induced
  • Parkinsonian Disorders / drug therapy*
  • Parkinsonian Disorders / metabolism
  • Parkinsonian Disorders / pathology*
  • Rats
  • Rats, Sprague-Dawley
  • Stem Cell Transplantation
  • Terpenes / pharmacology*
  • Tyrosine 3-Monooxygenase / biosynthesis
  • Tyrosine 3-Monooxygenase / metabolism

Substances

  • Cyclohexenes
  • Dopamine Plasma Membrane Transport Proteins
  • Terpenes
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins
  • safranal
  • Oxidopamine
  • Tyrosine 3-Monooxygenase
  • Dopamine