title: Neuroprotective effects of quercetin in a mouse model of brain ischemic/reperfusion injury via anti-apoptotic mechanisms based on the Akt pathway.
abstract: The present study provided experimental evidence for the neuroprotective effects of quercetin using a rat model of global brain ischemic/reperfusion (I/R) injury. Pre‑treatment with quercetin (5 or 10 mg/kg orally (p.o.); once daily) induced a dose‑dependent reduction in I/R‑induced hippocampal neuron cell loss, with 10 mg/kg/day being the lowest dose that achieved maximal neuroprotection. Administration of 10 mg/kg quercetin over at least 3 days prior to I/R was required to improve the survival rate of I/R rats. Fluorescence‑assisted cell sorting, hematoxylin and eosin staining and terminal deoxynucleotidyl transferase dUTP nick end labeling indicated neuronal cell loss in the CA1 hippocampus. Rats that had undergone transient global cerebral ischemia for 15 min followed by 1 h of reperfusion exhibited a significant increase in reactive oxygen species (ROS) production in the hippocampus. The I/R‑induced ROS overproduction in the hippocampus at 1, 12 and 24 h following I/R was significantly decreased by quercetin pre‑treatment. Western blot analysis revealed that the neuroprotective effects of quercetin (5 and 10 mg/kg/day, p.o.) were associated with an upregulation of the I/R‑induced suppression of B‑cell lymphoma‑2 (Bcl‑2), Bcl extra large and survivin expression as well as phosphorylation of Bcl‑2‑associated death promoter. Furthermore, the neuroprotective effects of quercetin (5, 10 mg/kg/day) in the brain were associated with an upregulation of Akt signaling. These findings suggested that the inhibition of I/R‑induced brain injury by quercetin likely involves a transcriptional mechanism to enhance anti‑apoptotic signaling.
authors.affiliation: Department of Anesthesiology, Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Lei
authors.affiliation: Department of Anesthesiology, Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Hailian
authors.initials: H
authors.lastname: Chao
authors.affiliation: Department of Anesthesiology, Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Zhenni
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Jianrui
authors.initials: J
authors.lastname: Lv
authors.affiliation: Department of Anesthesiology, Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Siyuan
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Haidong
authors.initials: H
authors.lastname: Wei
authors.affiliation: Department of Anesthesiology, Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Rongliang
authors.initials: R
authors.lastname: Xue
authors.affiliation: Department of Anesthesiology, Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Fang
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of General Surgery, Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Zongfang
authors.initials: Z
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008568:Memory / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011794:Quercetin / Q000627:therapeutic use*; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D065853:Spatial Learning / Q000187:drug effects
chemical_list: D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D011794:Quercetin; D051057:Proto-Oncogene Proteins c-akt