Strongylophorine-8, a pro-electrophilic compound from the marine sponge Petrosia (Strongylophora) corticata, provides neuroprotection through Nrf2/ARE pathway |
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Authors: | Sasaki Shunsuke Tozawa Terumasa Van Wagoner Ryan M Ireland Chris M Harper Mary Kay Satoh Takumi |
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Affiliation: | aDepartment of Welfare Engineering, Faculty of Engineering, Iwate University, Morioka, Iwate 020-8551, Japan;bDepartment of Medicinal Chemistry, University of Utah, 30 South 2000 East, Salt Lake City, UT 84112, United States |
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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 marine organisms 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 strongylophorine-8 (STR8), a para-hydroquinone-type pro-electrophilic compound from the sponge Petrosia (Strongylophora) corticata. STR8 activated the Nrf2/ARE pathway, induced phase 2 enzymes, and increased glutathione, thus protecting neuronal cells from oxidative stress. Microarray analysis indicated that STR8 induced a large number of phase 2 genes, the regulation of which is controlled by the Nrf2/ARE pathway. STR8 is the first example of a neuroprotective pro-electrophilic compound from marine organisms. |
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Keywords: | Strongylophorine-8 ARE Nrf2 Pro-electrophilic drugs Para-hydroquinone |
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