title: Neuroprotection of early and short-time applying berberine in the acute phase of cerebral ischemia: up-regulated pAkt, pGSK and pCREB, down-regulated NF-κB expression, ameliorated BBB permeability.
abstract: Berberine (BBR) has gained attention for its vast beneficial biological effects through immunomodulation, anti-inflammatory and anti-apoptosis properties. Inflammatory and apoptosis damage play an important role in cerebral ischemic pathogenesis and may represent a target for treatment. The aim of this study was to explore BBR's effect in ischemic injury and the role of the Akt/GSK (glycogen synthase kinase) signaling cascade in mediating the anti-apoptosis and anti-inflammatory effects in the rat brain of permanent middle cerebral artery occlusion (pMCAO). Male Sprague-Dawley rats were subjected to pMCAO and randomly assigned into four groups: Sham (sham-operated) group, pMCAO (pMCAO+0.9% saline) group, BBR-L (pMCAO+BBR 10 mg/kg) and BBR-H (pMCAO+BBR 40 mg/kg) group. BBR was administered immediately after pMCAO and the neuroprotection was detected. Phospho-Akt (pAkt), phospho-glycogen synthase kinase 3-β (pGSK3β), phospho-cAMP response element binding protein (pCREB), nuclear factor-kappa B (NF-κB) and claudin-5 in ischemic cerebral cortex were detected by immunohistochemistry, reverse transcription-polymerase chain reaction and western blotting. Compared with pMCAO group, BBR dramatically lessened neurological deficits scores, brain water contents and infarct sizes, upregulated the expression of pAkt, pGSK3β, pCREB and claudin-5, and decreased the nuclear accumulation of NF-κB (P<0.05) in ischemic brain. The results showed that BBR reduced ischemic brain injury after pMACO, and this effect may be via the increasing the activation of Akt/GSK signaling and claudin-5, and decreasing NF-κB expression.
authors.affiliation: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Zhang
authors.forename: Xiangjian
authors.initials: X
authors.lastname: Zhang
authors.forename: Chaohui
authors.initials: C
authors.lastname: Wang
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Li
authors.forename: Lipeng
authors.initials: L
authors.lastname: Dong
authors.forename: Lili
authors.initials: L
authors.lastname: Cui
authors.forename: Lina
authors.initials: L
authors.lastname: Wang
authors.forename: Zongjie
authors.initials: Z
authors.lastname: Liu
authors.forename: Huimin
authors.initials: H
authors.lastname: Qiao
authors.forename: Chunhua
authors.initials: C
authors.lastname: Zhu
authors.forename: Yinxue
authors.initials: Y
authors.lastname: Xing
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Cao
authors.forename: Ye
authors.initials: Y
authors.lastname: Ji
authors.forename: Kang
authors.initials: K
authors.lastname: Zhao
mesh_terms: D000818:Animals; D001599:Berberine / Q000008:administration & dosage* / Q000737:chemistry; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000473:pathology; D001929:Brain Edema / Q000209:etiology / Q000517:prevention & control; D050882:CREB-Binding Protein / Q000235:genetics / Q000378:metabolism; D002544:Cerebral Infarction / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D005786:Gene Expression Regulation / Q000187:drug effects*; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000188:drug therapy*; D008297:Male; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009422:Nervous System Diseases / Q000209:etiology / Q000517:prevention & control; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000737:chemistry; D051058:Oncogene Protein v-akt / Q000235:genetics / Q000378:metabolism; D010539:Permeability / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D016328:NF-kappa B; D018696:Neuroprotective Agents; D001599:Berberine; D050882:CREB-Binding Protein; D000071679:Glycogen Synthase Kinase 3 beta; D051058:Oncogene Protein v-akt; D038362:Glycogen Synthase Kinase 3