Purple rice extract and its constituents suppress endoplasmic reticulum stress-induced retinal damage in vitro and in vivo.

Junji Tanaka, Tomohiro Nakanishi, Hiroshi Shimoda, Seikou Nakamura, Kazuhiro Tsuruma, Masamitsu Shimazawa, Hisashi Matsuda, Masayuki Yoshikawa, Hideaki Hara

Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan.

Life sciences 2013 Jan 17

filter terms:

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. 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. 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. 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. Copyright © 2012 Elsevier Inc. All rights reserved.

Citation

Junji Tanaka, Tomohiro Nakanishi, Hiroshi Shimoda, Seikou Nakamura, Kazuhiro Tsuruma, Masamitsu Shimazawa, Hisashi Matsuda, Masayuki Yoshikawa, Hideaki Hara. Purple rice extract and its constituents suppress endoplasmic reticulum stress-induced retinal damage in vitro and in vivo. Life sciences. 2013 Jan 17;92(1):17-25