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

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.