title: Dual protection of hydroxytyrosol, an olive oil polyphenol, against oxidative damage in PC12 cells.
abstract: Hydroxytyrosol (3,4-dihydroxyphenylethanol, HT), a major polyphenol in olive oils, has received increasing attention due to its multiple pharmacological activities. However, it is not well understood how HT works on the neuronal system. We report herein that HT efficiently scavenges free radicals in vitro and displays cytoprotection against oxidative stress-induced damage in PC12 cells. HT completely protects the cells from hydrogen peroxide-induced death and rescues the cells from 6-hydroxydopamine-induced damage. Mechanistic studies reveal that Nrf2 is a prerequisite for the neuroprotection of HT as knocking down Nrf2 eliminated this action. HT, via activation of the Keap1-Nrf2 pathway, elevates a panel of cytoprotective enzymes, including glutamate-cysteine ligase, HO-1, NQO1 and thioredoxin reductase. Our study reveals that HT provides dual neuroprotection and cellular antioxidant defense as both a free radical scavenger and Nrf2 activator, suggesting the potential pharmaceutical usage of HT for the treatment of neurodegenerative disorders.
authors.affiliation: State Key Laboratory of Applied Organic Chemistry and College of Chemistry and Chemical Engineering, Lanzhou, Gansu 730000, China. fangjg@lzu.edu.cn.
authors.forename: Shoujiao
authors.initials: S
authors.lastname: Peng
authors.forename: Baoxin
authors.initials: B
authors.lastname: Zhang
authors.forename: Juan
authors.initials: J
authors.lastname: Yao
authors.forename: Dongzhu
authors.initials: D
authors.lastname: Duan
authors.forename: Jianguo
authors.initials: J
authors.lastname: Fang
mesh_terms: D000818:Animals; D051381:Rats; D018663:Adrenergic Agents / Q000009:adverse effects / Q000737:chemistry; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D016166:Free Radical Scavengers / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000633:toxicity; D007700:Kinetics; D009419:Nerve Tissue Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D000069463:Olive Oil / Q000737:chemistry; D016877:Oxidants / Q000037:antagonists & inhibitors / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects; D016627:Oxidopamine / Q000009:adverse effects / Q000037:antagonists & inhibitors; D016716:PC12 Cells; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering; D015398:Signal Transduction / Q000187:drug effects; D051267:NF-E2-Related Factor 2
chemical_list: C005975:3,4-dihydroxyphenylethanol; D018663:Adrenergic Agents; D000975:Antioxidants; D016166:Free Radical Scavengers; D006861:Hydrogen Peroxide; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D000069463:Olive Oil; D016877:Oxidants; D016627:Oxidopamine; D010626:Phenylethyl Alcohol; D017382:Reactive Oxygen Species; D034741:RNA, Small Interfering; D051267:NF-E2-Related Factor 2