title: Activation of the Nrf2 defense pathway contributes to neuroprotective effects of phloretin on oxidative stress injury after cerebral ischemia/reperfusion in rats.
abstract: Oxidative stress is considered a major contributing factor in cerebral ischemia/reperfusion injury. Phloretin, a dihydrochalcone belonging to the flavonoid family, is particularly rich in apples and apple-derived products. A large body of evidence demonstrates that phloretin exhibits anti-oxidant properties, and phloretin has potential implications for treating oxidative stress injuries in cerebral ischemia/reperfusion. Therefore, the neuroprotective and antioxidant effects of phloretin against ischemia/reperfusion injury, as well as related probable mechanisms, were investigated. The cerebral ischemic/reperfusion injury model was reproduced in male Sprague-Dawley rats through middle cerebral artery occlusion. At 24h after reperfusion, neurological score, infarct volume, and brain water content were assessed. Oxidative stress was evaluated by superoxide dismutases (SOD), glutathione (GSH), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) levels. Nrf2 expression was measured by RT-PCR and western blot. Consequently, results showed that phloretin pretreatment for 14days significantly reduced infarct volume and brain edema, and ameliorated neurological scores in focal cerebral ischemia/reperfusion rats. SOD, GSH and GSH-Px activities were greatly decreased, and MDA levels significantly increased after ischemia/reperfusion injury. However, phloretin pretreatment dramatically suppressed these oxidative stress processes. Furthermore, phloretin upregulated Nrf2 mRNA and protein expression of in ischemia/reperfusion brain tissue. Taken together, phloretin exhibited neuroprotective effects in cerebral ischemia/reperfusion, and the mechanisms are associated with oxidative stress inhibition and Nrf2 defense pathway activation.
authors.affiliation: Shandong Province Qianfoshan Hospital Affiliated to Shandong University, Jinan, Shandong 250014, China; Department of Health Care, The Affiliated Hospital of Weifang Medical University, Weifang 261031, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Magnetic Resonance Image, Shandong Province Qianfoshan Hospital Affiliated to Shandong University, Jinan, Shandong 250014, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Health Care, Shandong Province Qianfoshan Hospital Affiliated to Shandong University, Jinan, Shandong 250014, China. Electronic address: sdliang123@163.com.
authors.forename: Jiangjiu
authors.initials: J
authors.lastname: Liang
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy*; D004195:Disease Models, Animal; D008297:Male; D053858:Metabolic Networks and Pathways; D051267:NF-E2-Related Factor 2 / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D010693:Phloretin / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy*; D015854:Up-Regulation
chemical_list: D051267:NF-E2-Related Factor 2; D018696:Neuroprotective Agents; C495637:Nfe2l2 protein, rat; D010693:Phloretin
keywords: Cerebral ischemia/reperfusion; GSH-Px; MDA; Nrf2; Phloretin; SOD