title: A novel di terpene para-hydroquinone compound derived from cryptoquinone protects neuronal cells against oxidative stress and activates the Nrf2/ARE pathway.
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.
authors: Department of Welfare Engineering, Faculty of Engineering, Iwate University, Morioka, Iwate 020-8551, Japan.
authors: Shunsuke
authors: S
authors: Sasaki
authors: Terumasa
authors: T
authors: Tozawa
authors: Kazuhiro
authors: K
authors: Sugamoto
authors: Yoh-ichi
authors: Y
authors: Matsushita
authors: Takumi
authors: T
authors: Satoh
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D006801:Humans; D006873:Hydroquinones / Q000138:chemical synthesis / Q000494:pharmacology*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D018696:Neuroprotective Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D006873:Hydroquinones; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D018696:Neuroprotective Agents; D002265:Carboxylic Ester Hydrolases; C019734:arylesterase
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