title: Calycosin-7-O-β-D-glucoside regulates nitric oxide /caveolin-1/matrix metalloproteinases pathway and protects blood-brain barrier integrity in experimental cerebral ischemia-reperfusion injury.
abstract: BACKGROUND
  Astragali Radix (AR) has been used for thousands years to treat ischemic stroke. Calycosin and its glycoside form calycosin-7-O-β-D-glucoside (CG) are two representative isoflavones in Astragali Radix. However, its neurological effects and related molecular mechanisms are largely unknown. The present study aims to evaluate the neuroprotective effects of CG on blood-brain barrier (BBB) integrity of ischemic brain tissue and explore the relevant signaling mechanisms.
  
  
  METHODS
  Male adult Sprague-Daweley rats were subjected to 2 h of middle cerebral artery occlusion (MCAO) plus 24 h or 14 days of reperfusion. CG (26.8 mg/kg) was intraperitoneally administered into the rats at 15 min before onset of ischemia. The neuroprotective effects of CG were evaluated by measuring infarct volume, histological damage and BBB permeability. Furthermore, the effects of CG on scavenging nitric oxide (NO), and modulating matrix metalloproteinases (MMPs) and caveolin-1 (cav-1) were investigated with in vitro cultured brain microvascular endothelial cells treated with NO donor or oxygen-glucose deprivation (OGD) and/or in vivo rat model of MCAO cerebral ischemia-reperfusion injury.
  
  
  RESULTS
  CG treatment significantly reduced infarct volume, histological damage and BBB permeability in the in vivo MCAO ischemia-reperfusion rat model. CG treatment remarkably inhibited the expression and activities of MMPs, and secured the expression of cav-1 and tight junction proteins in the microvessels isolated from ischemic rat cortex. Furthermore, CG was revealed to scavenge NO, inhibit the activities of MMP-2 and MMP-9, and attenuate cell death in the in vitro cultured brain microvascular endothelial cells under OGD condition.
  
  
  CONCLUSIONS
  CG could protect BBB integrity in experimental cerebral ischemia-reperfusion injury via regulating NO/cav-1/MMPs pathway.
authors.affiliation: School of Chinese Medicine, The University of Hong Kong, 10 Sassoon Road, Pokfulam, Hong Kong SAR, China.
authors.forename: Shuping
authors.initials: S
authors.lastname: Fu
authors.affiliation: School of Chinese Medicine, The University of Hong Kong, 10 Sassoon Road, Pokfulam, Hong Kong SAR, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Department of Phytochemistry, China Pharmacology University, 24 Tongjia Alley, Gulou, Nanjing, Jiangsu, 210009, China.
authors.forename: Jian-Qin
authors.initials: JQ
authors.lastname: Jiang
authors.affiliation: School of Chinese Medicine, The University of Hong Kong, 10 Sassoon Road, Pokfulam, Hong Kong SAR, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: School of Chinese Medicine, The University of Hong Kong, 10 Sassoon Road, Pokfulam, Hong Kong SAR, China.
authors.forename: Mingjing
authors.initials: M
authors.lastname: Xu
authors.affiliation: School of Chinese Medicine, The University of Hong Kong, 10 Sassoon Road, Pokfulam, Hong Kong SAR, China.
authors.forename: Xingmiao
authors.initials: X
authors.lastname: Chen
authors.affiliation: School of Chinese Medicine, The University of Hong Kong, 10 Sassoon Road, Pokfulam, Hong Kong SAR, China; Research Center of Heart, Brain, Hormone & Health Aging, The University of Hong Kong, 10 Sassoon Road, Pokfulam, Hong Kong SAR, China. Electronic address: shenjg@hkucc.hku.hk.
authors.forename: Jiangang
authors.initials: J
authors.lastname: Shen
mesh_terms: D000818:Animals; D027883:Astragalus Plant / Q000737:chemistry; D001812:Blood-Brain Barrier / Q000378:metabolism; D002545:Brain Ischemia / Q000517:prevention & control*; D051242:Caveolin 1 / Q000378:metabolism; D004195:Disease Models, Animal; D005960:Glucosides / Q000302:isolation & purification / Q000494:pharmacology*; D007529:Isoflavones / Q000302:isolation & purification / Q000494:pharmacology*; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D055806:Microvessels / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000503:physiopathology; D062725:Tight Junction Proteins / Q000378:metabolism; D013997:Time Factors
chemical_list: D051242:Caveolin 1; D005960:Glucosides; D007529:Isoflavones; D018696:Neuroprotective Agents; D062725:Tight Junction Proteins; C526426:calycosin-7-O-beta-D-glucoside; D009569:Nitric Oxide; D020782:Matrix Metalloproteinases
keywords: Calyscosin-7-O-β-d-glucoside; Caveolin-1; Cerebral ischemia–reperfusion injury; Matrix metalloproteinases; Nitric oxide