title: Purple rice extract and its constituents suppress endoplasmic reticulum stress-induced retinal damage in vitro and in vivo.
abstract: OBJECTIVE
  Endoplasmic reticulum (ER) stress has been implicated as a cause of various neurodegenerative diseases. We evaluated the protective effects of purple rice (Oryza sativa L.) bran extract (PRE) and its constituents, namely cyanidin, peonidin, and a newly isolated compound 2-hydroxy-5-[(3S)-3-hydroxybutyl]phenyl-β-D-glucoside (HHPG), against tunicamycin-induced retinal damage.
  
  
  METHODS
  In an in vitro experiment, protective effects of PRE, cyanidin and HHPG on cultured retinal ganglion cells (RGC-5), which were damaged by treatment with H(2)O(2) or tunicamycin for 24 h, were evaluated. We also investigated the underlying mechanism by examining expressions of ER stress-related proteins, such as immunoglobulin heavy-chain binding protein (BiP) and C/EBP homologous protein (CHOP), and activation of caspase-3 induced by tunicamycin. In an in vivo experiment, mice retinal damage was induced by intravitreous injection of tunicamycin as revealed by histological analysis using hematoxylin-eosin staining.
  
  
  RESULTS
  The viability of H(2)O(2) or tunicamycin-treated RGC-5, assessed using the tetrazolium salt (WST-8) assay, was improved by treatment with PRE, cyanidin, and HHPG, respectively. PRE did not affect tunicamycin-induced expressions of BiP or CHOP. However, PRE, cyanidin, and HHPG suppressed tunicamycin-induced caspase-3 activation. Histological analysis using hematoxylin-eosin staining showed that intravitreous injection of PRE significantly suppressed the tunicamycin-induced degeneration of retinal ganglion cells in mice.
  
  
  CONCLUSIONS
  These findings indicate that PRE, cyanidin, and HHPG suppress tunicamycin-induced retinal ganglion cell death at least partly by inhibiting activation of caspase-3, suggesting that PRE and its main constituents prevent retinal disease caused by ER stress.
authors.affiliation: Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Tanaka
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Nakanishi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shimoda
authors.forename: Seikou
authors.initials: S
authors.lastname: Nakamura
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tsuruma
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Shimazawa
authors.forename: Hisashi
authors.initials: H
authors.lastname: Matsuda
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yoshikawa
authors.forename: Hideaki
authors.initials: H
authors.lastname: Hara
mesh_terms: D000818:Animals; D000872:Anthocyanins / Q000302:isolation & purification / Q000494:pharmacology; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D005960:Glucosides / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000633:toxicity; D008297:Male; D051379:Mice; D012275:Oryza / Q000737:chemistry*; D010936:Plant Extracts / Q000494:pharmacology*; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000473:pathology; D014415:Tunicamycin / Q000633:toxicity
chemical_list: C578400:2-hydroxy-5-((3S)-3-hydroxybutyl)phenyl-beta-D-glucoside; D000872:Anthocyanins; D005960:Glucosides; D010936:Plant Extracts; D014415:Tunicamycin; C017154:cyanidin; D006861:Hydrogen Peroxide; D053148:Caspase 3