title: Neuroprotective effect of fermented papaya preparation by activation of Nrf2 pathway in astrocytes.
abstract: OBJECTIVE
  Nuclear factor erythroid 2-related factor (Nrf2) in astrocyte plays important roles in brain homeostasis. Fermented papaya preparation (FPP) has anti-oxidative, anti-inflammatory, immunoregulatory properties. The present study investigated the effects of FPP on activation of Nrf2 and release of Nrf2-regulated neuroprotective antioxidants and detoxifying molecules.
  
  
  METHODS
  Primary cultured astrocytes from rat embryos were treated with FPP for 6 or 24 hours. The expression levels of nuclear Nrf2 and cytoplasmic Nrf2-regulated molecules were determined by western blot analysis and immunohistochemistry. Glutathione levels were measured in cells and medium. Dopaminergic neurons were exposed 6-hydroxydopamine (6-OHDA) with/without pre-treatment with FPP astrocytes. Mice were treated orally with FPP for 2 weeks.
  
  
  RESULTS
  FPP increased nuclear translocation of Nrf2 in striatal astrocytes, induced up-regulation of NAD(P)H quinine oxidoreductase-1, glutathione-S transferase and hemeoxygenase-1, and increased glutathione level and the percentage of metallothionein-expressing astrocytes. Moreover, FPP suppressed 6-OHDA-induced dopaminergic neuronal loss in not only neuron-astrocyte mixed culture, but also neuron-rich cultures pre-treated with glial conditioned medium. Two-week oral treatment of mice with FPP resulted in Nrf2 activation and increase in glutathione level in striatum.
  
  
  CONCLUSIONS
  The results indicated that FPP enhances the anti-oxidative capacity through activation of Nrf2 in astrocytes, suggesting it may provide neuroprotection in oxidative stress-related neurodegenerative diseases.
authors.affiliation: a Department of Medical Neurobiology , Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences , Okayama , Japan.|b SAIDO Corporation , Fukuoka , Japan.
authors.forename: Shinki
authors.initials: S
authors.lastname: Murakami
authors.affiliation: a Department of Medical Neurobiology , Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences , Okayama , Japan.
authors.forename: Ikuko
authors.initials: I
authors.lastname: Miyazaki
authors.affiliation: a Department of Medical Neurobiology , Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences , Okayama , Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Asanuma
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000378:metabolism; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D029441:Carica / Q000737:chemistry* / Q000254:growth & development; D002478:Cells, Cultured; D000073417:Dietary Sugars / Q000008:administration & dosage / Q000378:metabolism; D019587:Dietary Supplements / Q000382:microbiology; D059290:Dopaminergic Neurons / Q000166:cytology / Q000378:metabolism; D005285:Fermentation; D005333:Fetus / Q000166:cytology; D005638:Fruit / Q000737:chemistry* / Q000254:growth & development; D005947:Glucose / Q000008:administration & dosage / Q000378:metabolism; D008297:Male; D008636:Mesencephalon / Q000166:cytology / Q000378:metabolism; D008813:Mice, Inbred ICR; D051267:NF-E2-Related Factor 2 / Q000819:agonists* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000819:agonists / Q000378:metabolism; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000378:metabolism*; D018384:Oxidative Stress; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D014793:Visual Cortex / Q000166:cytology / Q000378:metabolism
chemical_list: D000975:Antioxidants; D000073417:Dietary Sugars; D051267:NF-E2-Related Factor 2; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D005947:Glucose
keywords: Astrocyte; Fermented papaya preparation; Nrf2; Oxidative stress