title: Phenylbutenoid dimers isolated from Zingiber purpureum exert neurotrophic effects on cultured neurons and enhance hippocampal neurogenesis in olfactory bulbectomized mice.
abstract: Trans-3-(3'4'-dimethoxyphenyl)-4-[(E)-3",4"-dimethoxystyryl]cyclohex-1-ene (Comp.1) and cis-3-(3'4'-dimethoxyphenyl)-4-[(E)-3",4"-dimethoxystyryl]cyclohex-1-ene (Comp.2), phenylbutenoid dimers, have been isolated as neurotrophic molecules from an Indonesian medicinal plant, Zingiber purpureum. The aim of this study was to explore the neurotrophic effects of Comp.1 and Comp.2 in vitro and in vivo. Comp.1 (10-30 μM) or Comp.2 (30 μM) significantly induced neurite sprouting in PC12 cells. Comp.1 (0.03-3 μM) or Comp.2 (0.3-3 μM) significantly increased the neurite length and number of neurites in primary cultured rat cortical neurons. Comp.1 (30 μM) and Comp.2 (3-30 μM) also provided significant protection against cell death caused by deprivation of serum. The in vivo effects of both Comp.1 and Comp.2 were evaluated on hippocampal neurogenesis in olfactory bulbectomized (OBX) mice, an experimental depression and dementia animal model. Comp.1 (50mg/kg p.o.), Comp.2 (50mg/kg p.o.), or fluoxetine (10mg/kg i.p.), an antidepressant, were administrated once a day on days 15-28 after OBX. Neurogenesis was assessed by analysis of cells expressing NeuN, a neuronal marker, and 5-bromo-2'-deoxyuridine (BrdU) uptake. Immunohistochemical analysis showed that the number of BrdU/NeuN double-labeled cells in the dentate gyrus was significantly decreased 30 days after OBX. Chronic treatment with Comp.1, Comp.2 or fluoxetine significantly increased the number of BrdU/NeuN double-labeled cells. These results indicate that Comp.1 and Comp.2 have neurotrophic effects, and have the potential for disease modification in depression and dementia.
authors.affiliation: Faculty of Pharmaceutical Sciences, Tokushima Bunri University, 180 Nishihama-bouji, Yamashiro-cho, Tokushima 770-8514, Japan. matsui@ph.bunri-u.ac.jp
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Matsui
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kido
authors.forename: Hideki
authors.initials: H
authors.lastname: Okada
authors.forename: Miwa
authors.initials: M
authors.lastname: Kubo
authors.forename: Megumi
authors.initials: M
authors.lastname: Nakai
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Fukuishi
authors.forename: Yoshiyasu
authors.initials: Y
authors.lastname: Fukuyama
authors.forename: Masaaki
authors.initials: M
authors.lastname: Akagi
mesh_terms: D000818:Animals; D002087:Butyrates / Q000302:isolation & purification / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D005260:Female; D020939:Zingiber officinale / Q000737:chemistry*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development*; D007150:Immunohistochemistry; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D016501:Neurites / Q000187:drug effects; D055495:Neurogenesis / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents; D009830:Olfactory Bulb / Q000502:physiology*; D016716:PC12 Cells; D018517:Plant Roots / Q000737:chemistry; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002087:Butyrates; D018696:Neuroprotective Agents