Methylophiopogonanone A Protects against Cerebral Ischemia/Reperfusion Injury and Attenuates Blood-Brain Barrier Disruption In Vitro

• Published in: PloS one 2015-04, Vol.10 (4), p.e0124558-e0124558
• Main Authors: Lin, Mingbao, Sun, Wei, Gong, Wan, Zhou, Zhiyu, Ding, Yasi, Hou, Qi
• Format: Article
• Language: English
• Subjects: Analysis; Animals; Attenuation; Benzodioxoles - pharmacology; Benzodioxoles - therapeutic use; Blood-brain barrier; Blood-Brain Barrier - drug effects; Blood-Brain Barrier - metabolism; Body weight; Brain injury; Brain research; Cell Adhesion; Cell Line; Cerebral blood flow; Chinese medicine; Disruption; Drug Evaluation, Preclinical; Edema; Electron microscopy; Endothelium, Vascular - pathology; Gelatinase B; Humans; Hypoxia; Infarction, Middle Cerebral Artery - complications; Infarction, Middle Cerebral Artery - drug therapy; Inflammation; Injury prevention; Intercellular adhesion molecule 1; Ischemia; Isoflavones - pharmacology; Isoflavones - therapeutic use; Laboratory animals; Leukocytes; Leukocytes - physiology; Male; Metabolism; Mice; Neuroprotective Agents - pharmacology; Neuroprotective Agents - therapeutic use; Neurosciences; Occlusion; Ophiopogon japonicus; Oxidative stress; Permeability; Proteins; Rats, Sprague-Dawley; Reactive Oxygen Species - metabolism; Reperfusion; Reperfusion Injury - etiology; Reperfusion Injury - prevention & control; Rodents; Stroke; Thrombosis; Transmission electron microscopy; Vascular cell adhesion molecule 1; Western blotting
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0124558

Methylophiopogonanone A (MO-A), an active homoisoflavonoid of the Chinese herb Ophiopogon japonicus which has been shown to have protective effects on cerebral ischemia/reperfusion (I/R) injury, has been demonstrated to have anti-inflammatory and anti-oxidative properties. However, little is known about its role in cerebral I/R injury. Therefore, in this study, by using a middle cerebral artery occlusion (MCAO) and reperfusion rat model, the effect of MO-A on cerebral I/R injury was examined. The results showed that MO-A treatment reduced infarct volume and brain edema, improved neurological deficit scores, reversed animal body weight decreases, and increased animal survival time in the stroke groups. Western blotting showed that MO-A suppressed MMP-9, but restored the expression of claudin-3 and claudin-5. Furthermore, transmission electron microscopy were monitored to determine the blood-brain barrier (BBB) alterations in vitro. The results showed that MO-A markedly attenuated BBB damage in vitro. Additionally, MO-A inhibited ROS production in ECs and MMP-9 release in differentiated THP-1 cells in vitro, and suppressed ICAM-1 and VCAM-1 expression in ECs and leukocyte/EC adhesion. In conclusion, our data indicate that MO-A has therapeutic potential against cerebral I/R injury through its ability to attenuate BBB disruption by regulating the expression of MMP-9 and tight junction proteins.