title: Baicalin reduces the permeability of the blood-brain barrier during hypoxia in vitro by increasing the expression of tight junction proteins in brain microvascular endothelial cells.
abstract: BACKGROUND
  Baicalin is one of the principal flavonoids isolated from the dried root of Scutellariae Baicalensis Georgi and has been widely used as a traditional herbal medicine to suppress brain edema and reduce cerebral ischemic damage. However, the effects of baicalin on the blood-brain barrier (BBB) are poorly understood.
  
  
  OBJECTIVE
  To explore the effects of baicalin on the permeability of the BBB under ischemic conditions in vitro with regard to changes in the tight junctions(TJ) proteins claudin-5 and zonula occludens-1 (ZO-1).
  
  
  METHODS
  Brain microvascular endothelial cells(BMVECs) from Bal b/c mice were cultured to establish an in vitro BBB model. Oxygen and glucose deprivation (OGD) was applied to simulate ischemia. The experiment consisted of a normal control group, a model group and baicalin-treated groups (high-dose group, moderate-dose group and low-dose group). Transendothelial electrical resistance (TEER) and permeability to HRP were used as indicators of changes in BBB permeability. A real-time fluorescent quantitative assay was utilized to monitor the transcriptional changes in claudin-5 and ZO-1, and western blotting was used to detect the changes in protein expression of claudin-5, ZO-1 and PKC.
  
  
  RESULTS
  OGD led to a significant increase of permeability in this in vitro BBB model. Baicalin effectively decreased the permeability of the BBB, promoted transcription and expression of TJ proteins (claudin-5 and ZO-1) and reduced the levels of PKC.
  
  
  CONCLUSIONS
  We propose that baicalin is capable of restoring the barrier function of the BBB under ischemic conditions and this beneficial effect may be linked to the decreased expression of TJ proteins.
authors.affiliation: Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing 100700, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Zhu
authors.forename: Zhiyao
authors.initials: Z
authors.lastname: Wang
authors.forename: Yanwei
authors.initials: Y
authors.lastname: Xing
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Gao
authors.forename: Tao
authors.initials: T
authors.lastname: Ma
authors.forename: Lixia
authors.initials: L
authors.lastname: Lou
authors.forename: Jinning
authors.initials: J
authors.lastname: Lou
authors.forename: Ying
authors.initials: Y
authors.lastname: Gao
authors.forename: Shuoren
authors.initials: S
authors.lastname: Wang
authors.forename: Yongyan
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism; D015153:Blotting, Western; D002199:Capillary Permeability / Q000187:drug effects*; D015687:Cell Hypoxia; D002478:Cells, Cultured; D062507:Claudin-5; D057167:Claudins / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000302:isolation & purification / Q000494:pharmacology*; D017097:Electric Impedance; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D005419:Flavonoids / Q000302:isolation & purification / Q000494:pharmacology*; D005453:Fluorescence; D005947:Glucose / Q000172:deficiency; D008516:Medicine, Chinese Traditional; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D055806:Microvessels / Q000187:drug effects* / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D018517:Plant Roots; D010946:Plants, Medicinal; D011493:Protein Kinase C / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D031364:Scutellaria baicalensis / Q000737:chemistry; D019108:Tight Junctions / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D062826:Zonula Occludens-1 Protein
chemical_list: D062507:Claudin-5; D057167:Claudins; C491511:Cldn5 protein, mouse; D004365:Drugs, Chinese Herbal; D005419:Flavonoids; D008565:Membrane Proteins; D010750:Phosphoproteins; C569043:Tjp1 protein, mouse; D062826:Zonula Occludens-1 Protein; C038044:baicalin; D011493:Protein Kinase C; D005947:Glucose