title: Icariside II protects against cerebral ischemia-reperfusion injury in rats via nuclear factor-κB inhibition and peroxisome proliferator-activated receptor up-regulation.
abstract: Icariside II (IRS) is a metabolite of icariin, which is derived from Herba Epimedii. Although the potential therapeutic effects of icariin on ischemic brain injury were well-investigated; the role of IRS in ischemic stroke is still not addressed clearly. Therefore, the current study aimed to evaluate the effects of IRS on cerebral ischemia-reperfusion injury in rats. The rats were pre-treated by IRS (10 or 30 mg kg(-1), twice a day) for 3 days. After pre-treatment, a MCAO (middle cerebral artery occlusion) for 2 h followed by reperfusion for 24 h was applied on the rats to induce the cerebral ischemia injury model. The neurological deficit scores were assessed at 24 h after reperfusion, then animals were sacrificed, infarct volumes were determined by 2,3,5-triphenyltetrazolium chlorid (TTC) staining and protein expression levels of interleukin-1β (IL-1β), transforming growth factor-β1 (TGF-β1), inhibitory κB (IκB), nuclear factor κB (NF-κB) p65, peroxisome proliferator-activated receptor α (PPARα), and peroxisome proliferator-activated receptor γ (PPARγ) were assayed by using Western blot. IRS pretreatment markedly improved the neurological dysfunction and decreased infarct volume in MCAO rats. In addition, IRS inhibited IL-1β and TGF-β1 protein expression, and resulted in beneficial effects such as inhibition of IκB-α degradation and NF-κB activation induced by MCAO, in a dose-dependent manner. Furthermore, IRS increased the protein expression levels of PPARα and PPARγ in the ischemic brain. In conclusion, pretreatment with IRS protects against cerebral ischemic/reperfusion injury via up-regulation of PPARα and PPARγ and inhibition of NF-κB activation.
authors.affiliation: Department of Pharmacology and the Key Laboratory of Basic Pharmacology of Ministry of Education, Zunyi Medical University, Zunyi, 563000, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Department of Pharmacology and the Key Laboratory of Basic Pharmacology of Ministry of Education, Zunyi Medical University, Zunyi, 563000, China.
authors.forename: Deqing
authors.initials: D
authors.lastname: Xiong
authors.affiliation: Department of Pharmacology and the Key Laboratory of Basic Pharmacology of Ministry of Education, Zunyi Medical University, Zunyi, 563000, China.
authors.forename: Caixia
authors.initials: C
authors.lastname: Yin
authors.affiliation: Department of Pharmacology and the Key Laboratory of Basic Pharmacology of Ministry of Education, Zunyi Medical University, Zunyi, 563000, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Pharmacology and the Key Laboratory of Basic Pharmacology of Ministry of Education, Zunyi Medical University, Zunyi, 563000, China.
authors.forename: Jingshan
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Pharmacology and the Key Laboratory of Basic Pharmacology of Ministry of Education, Zunyi Medical University, Zunyi, 563000, China. Electronic address: gqh@zmc.edu.cn.
authors.forename: Qihai
authors.initials: Q
authors.lastname: Gong
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use; D005419:Flavonoids / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D047493:PPAR alpha / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D004365:Drugs, Chinese Herbal; D005419:Flavonoids; D016328:NF-kappa B; D018696:Neuroprotective Agents; D047493:PPAR alpha; D047495:PPAR gamma; C060988:baohuoside I
keywords: Cerebral ischemia; Icariside II; Inflammation; Nuclear factor κB; Peroxisome proliferator-activated receptor