Astragaloside IV attenuates cerebral ischemia-reperfusion-induced increase in permeability of the blood-brain barrier in rats.
Astragalus membranaceus is widely used to treat stroke and chronic debilitating diseases in China, but the mechanism has not been fully demonstrated to data. In the present study, we, using astragaloside IV, a purified extract from astragalus membranaceus, to a focal cerebral ischemia/reperfusion rat model, aimed to investigate the effect of astragaloside IV on the permeability of the blood-brain barrier since disruption of blood-brain barrier induced by ischemia/reperfusion leads to serious brain injuries. We found that astragaloside IV (10, 20 mg/kg) significantly attenuated the permeability of blood-brain barrier in comparison with vehicle group after ischemia/reperfusion assessed via Evans blue leakage (P<0.05). This was further confirmed by examination of blood-brain barrier permeability under the electron microscope, using lanthanum as a tracer of blood vessel permeability. Lanthanum was usually found within the blood vessel in sham group, rather than in perivascular tissues as shown in vehicle group. In drug groups, lanthanum stain was mainly restricted within the cerebral capillary, indicating the potential protective effect of astragaloside IV on the integrity of blood-brain barrier in ischemia/reperfusion rats. Furthermore, we found that expression of occludin and zonae occludens-1 (ZO-1), the tight junction proteins, was decreased in endothelial cells in vehicle group, which, however, could be reversed by astragaloside IV administration. We propose that regulation of tight junctional proteins in the endothelial cells may be one mechanism astragaloside IV-mediated in attribution to blood-brain barrier protection in the ischemia/reperfusion rats.
Department of Neurosurgery, Tangdu Hospital and Institute for Functional Brain Disorders, Baqiao District, Xi'an, PR China.
You Zhi
YZ
Qu
Min
M
Li
Yan Ling
YL
Zhao
Zhen Wei
ZW
Zhao
Xiao Yan
XY
Wei
Jin Ping
JP
Liu
Li
L
Gao
Guo Dong
GD
Gao
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism* / Q000648:ultrastructure; D002545:Brain Ischemia / Q000150:complications* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008854:Microscopy, Electron; D062793:Occludin; D010539:Permeability / Q000187:drug effects; D010750:Phosphoproteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications* / Q000378:metabolism* / Q000473:pathology; D012503:Saponins / Q000494:pharmacology*; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism; D014315:Triterpenes / Q000494:pharmacology*; D062826:Zonula Occludens-1 Protein
D008565:Membrane Proteins; D062793:Occludin; C568987:Ocln protein, rat; D010750:Phosphoproteins; D012503:Saponins; C569044:Tjp1 protein, rat; D014315:Triterpenes; D062826:Zonula Occludens-1 Protein; C052064:astragaloside A