title: Eriodictyol protects against H(2)O(2)-induced neuron-like PC12 cell death through activation of Nrf2/ARE signaling pathway.
abstract: Eriodictyol, a flavonoid isolated from the Chinese herb Dracocephalum rupestre has long been established as an antioxidant. The present study was designed to explore the protective effects of eriodictyol against hydrogen peroxide (H(2)O(2))-induced neurotoxicity with cultured rat pheochromocytoma cells (PC12 cells) and the possible mechanisms involved. For this purpose, differentiated PC12 cells were cultured and exposed to 200 μM H(2)O(2) in the absence or presence of eriodictyol (20, 40 and 80 μM). In addition, the potential contribution of the Nrf2/ARE neuroprotective pathway in eriodictyol-mediated protection against H(2)O(2)-induced neurotoxicity was also investigated. The results showed that H(2)O(2)-induced cell death can be inhibited in the presence of eriodictyol as measured by assays for MTT and apoptosis. Further study revealed that eriodictyol induced the nuclear translocation of Nrf2, enhanced the expression of heme oxygenase (HO-1) and γ-glutamylcysteine synthetase (γ-GCS), and increased the levels of intracellular glutathione. Treatment of PC12 cells with Nrf2 small interference RNA abolished eriodictyol-induced HO-1 and γ-GCS expression and its protective effects. In conclusion, these results suggest that eriodictyol upregulates HO-1 and γ-GCS expression through the activation of Nrf2/ARE pathway and protects PC12 cells against H(2)O(2)-induced oxidative stress.
authors.affiliation: Department of Pharmacology, School of Medicine, Shandong University, Jinan 250012, PR China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Lou
authors.forename: Xu
authors.initials: X
authors.lastname: Jing
authors.forename: Dongmei
authors.initials: D
authors.lastname: Ren
authors.forename: Xinbing
authors.initials: X
authors.lastname: Wei
authors.forename: Xiumei
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D051381:Rats; D061745:Antioxidant Response Elements / Q000502:physiology; D000975:Antioxidants; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D016923:Cell Death / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D044950:Flavanones / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000633:toxicity; D007202:Indicators and Reagents; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents; D016877:Oxidants / Q000633:toxicity; D016716:PC12 Cells; D017382:Reactive Oxygen Species / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D051267:NF-E2-Related Factor 2 / Q000502:physiology
chemical_list: D000975:Antioxidants; C007619:eriodictyol; D044950:Flavanones; D005978:Glutathione; D006861:Hydrogen Peroxide; D007202:Indicators and Reagents; D018696:Neuroprotective Agents; D016877:Oxidants; D017382:Reactive Oxygen Species; D034741:RNA, Small Interfering; D051267:NF-E2-Related Factor 2