title: Diosgenin attenuates the brain injury induced by transient focal cerebral ischemia-reperfusion in rats.
abstract: The aim of the present study is to explore the potential cerebroprotection of diosgenin against the transient focal cerebral ischemia-reperfusion (I/R) injury and its possible underlying mechanisms. The diosgenin at two dose levels, namely 100 and 200mgkg(-1), was intragastrically administrated once daily for 7-day period prior to the surgery. Then, the rats were subjected to middle cerebral artery occlusion (MCAO) using the intraluminal thread for 90min. After 24h reperfusion, several diagnostic indicators were evaluated and all animals were sacrificed to harvest their brains and blood for subsequent biochemical analyses. The results indicated that diosgenin treatment significantly inhibited the death rate and improved the impaired neurological functions along with neurological deficit scores and cerebral infarct size as compared with the rats exposed to I/R insult without agents administration. The increase in the number of apoptotic cells determined by TUNEL in the hippocampus CA1 and cortex was also apparently attenuated in the diosgenin treatment group, which was closely correlated with suppression of Caspase-3 activity and Bax/Bcl-2 ratio. In addition the elevated concentrations of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) in blood serum of the I/R treated rats were reduced almost to their normal level. Further results obtained from the Western blotting analysis revealed that the protein expression of IκBα in the injured brain was up-regulated, while the p65 subunit of NF-κB was down-regulated in nucleus after the treatment. Collectively, this neuroprotection of diosgenin against I/R injury may be attained through its anti-apoptosis, anti-inflammation and intervening the NF-κB signal pathway properties. Due to the satisfactory findings, diosgenin might be a powerful therapeutic agent to combat the similar disease in future clinic.
authors.affiliation: College of Pharmacy, Xi'an Jiaotong Univeristy, Xi'an 710061, China.
authors.forename: Xinxin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: College of Pharmacy, Xi'an Jiaotong Univeristy, Xi'an 710061, China.
authors.forename: Xuanji
authors.initials: X
authors.lastname: Xue
authors.affiliation: College of Pharmacy, Xi'an Jiaotong Univeristy, Xi'an 710061, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: College of Pharmacy, Xi'an Jiaotong Univeristy, Xi'an 710061, China.
authors.forename: Chunxiang
authors.initials: C
authors.lastname: Qian
authors.affiliation: College of Pharmacy, Xi'an Jiaotong Univeristy, 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; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D001930:Brain Injuries / Q000188:drug therapy* / Q000209:etiology* / Q000378:metabolism; D002545:Brain Ischemia / Q000150:complications*; D004144:Diosgenin / Q000627:therapeutic use*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications*
chemical_list: D000893:Anti-Inflammatory Agents; D016328:NF-kappa B; D004144:Diosgenin
keywords: Anti-apoptosis; Anti-inflammation; Diosgenin; Ischemia-reperfusion injury; Middle cerebral artery occlusion; NF-κB