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Neurosci Lett. 2013 Aug 26;548:132-6. doi: 10.1016/j.neulet.2013.04.047. Epub 2013 May 3.

A novel di terpene para-hydroquinone compound derived from cryptoquinone protects neuronal cells against oxidative stress and activates the Nrf2/ARE pathway.

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  • 1Department of Welfare Engineering, Faculty of Engineering, Iwate University, Morioka, Iwate 020-8551, Japan.

Abstract

Green plant-origin electrophilic compounds are a newly recognized class of neuroprotective compounds that provide neuroprotection through activation of the Nrf2/ARE pathway. Electrophilic hydroquinones are of particular interest due to their ability to become electrophilic quinones upon auto-oxidation. Although green plants frequently produce a variety of electrophilic compounds, the detailed mechanisms of action of these compounds remain unknown. Here, we focused on the neuroprotective effects of 11,14-dihydroxy-8,11,13-abietariene (DA1), derived from a para-hydroquinone-type pro-electrophilic compound from the cryptoquinone. DA1 activated the Nrf2/ARE pathway, induced phase 2 enzymes, and increased glutathione, thus protecting neuronal cells from oxidative stress. DA1 had a very broad safety zone (199.41 fold) at least in our system. Thus, DA1 is a novel neuroprotective pro-electrophilic diterpene from green plant.

Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

KEYWORDS:

3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide; ARE; CA; Cryptoquinone; DA1; DMSO; FDA; GCLC; GSH; GSSG; GST; H(2)O(2); HO-1; MTT; NADPH quinone oxidoreductase 1; NQO-1; Nrf2; PED; Pro-electrophilic drugs; RT-PCR; SD; STR; antioxidant-responsive element; carnosic acid; dimethyl sulfoxide; fluorescein diacetate; glutamyl cysteine ligase catalytic subunit; glutathione S-transferase; heme oxygenase-1; hydrogen peroxide; oxidized glutathione; para-Hydroquinone; pro-electrophilic drug; reduced glutathione; reverse transcription-polymerase chain reaction; standard deviation; strongylophorine

PMID:
23648389
[PubMed - indexed for MEDLINE]
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