Strongylophorine-8, a pro-electrophilic compound from the marine sponge Petrosia (Strongylophora) corticata, provides neuroprotection through Nrf2/ARE pathway

• Published in: Biochemical and biophysical research communications Vol. 415; no. 1; pp. 6 - 10
• Main Authors: Sasaki, Shunsuke, Tozawa, Terumasa, Van Wagoner, Ryan M., Ireland, Chris M., Harper, Mary Kay, Satoh, Takumi
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 11.11.2011
• Subjects: Animals; Antioxidants - pharmacology; ARE; Cell Line; Humans; Marine; Neurons - drug effects; Neurons - metabolism; Neuroprotective Agents - chemistry; Neuroprotective Agents - isolation & purification; Neuroprotective Agents - pharmacology; NF-E2-Related Factor 2 - metabolism; Nrf2; Oxidative Stress - drug effects; Para-hydroquinone; Petrosia; Petrosia - chemistry; Pro-electrophilic drugs; Response Elements - drug effects; Strongylophora corticata; Strongylophorine-8; GSSG; NQO-1; PAT; DMSO; Strongylophorine-8; Para-hydroquinone; GST; HO-1; Pro-electrophilic drugs; MTT; PED; STR; SD; GCLC; ARE; Nrf2; RT-PCR; GSH; CA
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2011.09.114

► Strongylophorine-8 protected neuronal cells by activating the Keap1/Nrf2 pathway. ► Its para-hydroquinone is essential for the protective effects. ► This is the first report of neuroprotective pro-electrophile from marine organisms. 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.