title: Potential neuroprotection of protodioscin against cerebral ischemia-reperfusion injury in rats through intervening inflammation and apoptosis.
abstract: The aim of the current research is to investigate the cerebral-protection of protodioscin on a transient cerebral ischemia-reperfusion (I/R) model and to explore its possible underlying mechanisms. The rats were preconditioned with protodioscin at the doses of 25 and 50mgkg(-1) prior to surgery. Then the animals were subjected to right middle cerebral artery occlusion (MCAO) using an intraluminal method by inserting a thread (90min surgery). After the blood flow was restored in 24h via withdrawing the thread, some representative indicators for the cerebral injury were evaluated by various methods including TTC-staining, TUNEL, immunohistochemistry, and Western blotting. As compared with the operated rats without drug intervening, treatment with protodioscin apparently lowered the death rate and improved motor coordination abilities through reducing the deficit scores and cerebral infarct volume. What's more, an apparent decrease in neuron apoptosis detected in hippocampus CA1 and cortex of the ipsilateral hemisphere might attribute to alleviate the increase in Caspase-3 and Bax/Bcl-2 ratio. Meanwhile, concentrations of several main pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) in the serum were also significantly suppressed. Finally, the NF-κB and IκBa protein expressions in the cytoplasm of right injured brain were remarkably up-regulated, while NF-κB in nucleus was down-regulated. Therefore, these observed findings demonstrated that protodioscin appeared to reveal potential neuroprotection against the I/R injury due to its anti-inflammatory and anti-apoptosis properties. This therapeutic effect was probably mediated by the inactivation of NF-κB signal pathways.
authors.affiliation: College of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Xinxin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: College of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Xuanji
authors.initials: X
authors.lastname: Xue
authors.affiliation: College of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Xian
authors.affiliation: College of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, China. Electronic address: guozj@mail.xjtu.edu.cn.
authors.forename: Zengjun
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Laboratory of Bioseparation Technology, Biochemistry and Biophysics Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Ito
authors.affiliation: Biomedicine Key Laboratory of Shaanxi Province, Northwest University, Xi'an 710069, China. Electronic address: cxbml360@126.com.
authors.forename: Wenji
authors.initials: W
authors.lastname: Sun
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism; D004144:Diosgenin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D000066829:Neuroprotection / Q000187:drug effects; D018696:Neuroprotective Agents / Q000737:chemistry / Q000627:therapeutic use*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy*; D012503:Saponins / Q000737:chemistry / Q000627:therapeutic use*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D012503:Saponins; D051028:bcl-2-Associated X Protein; C459619:protodioscin; D004144:Diosgenin
keywords: Bax/Bcl-2 ratio; Caspase-3; Middle cerebral artery occlusion; NF-κB; Pro-inflammatory cytokines; Protodioscin