title: Methylophiopogonanone A Protects against Cerebral Ischemia/Reperfusion Injury and Attenuates Blood-Brain Barrier Disruption In Vitro.
abstract: 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.
authors.affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Mingbao
authors.initials: M
authors.lastname: Lin
authors.affiliation: Clinical Laboratory Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Sun
authors.affiliation: College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, China.
authors.forename: Wan
authors.initials: W
authors.lastname: Gong
authors.affiliation: College of Basic Medical Science, Jiangxi University of Traditional Chinese Medicine, NanChang, China.
authors.forename: Zhiyu
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Yasi
authors.initials: Y
authors.lastname: Ding
authors.affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Hou
mesh_terms: D000818:Animals; D052117:Benzodioxoles / Q000494:pharmacology* / Q000627:therapeutic use; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism; D002448:Cell Adhesion; D002460:Cell Line; D004353:Drug Evaluation, Preclinical; D004730:Endothelium, Vascular / Q000473:pathology; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000188:drug therapy*; D007529:Isoflavones / Q000494:pharmacology* / Q000627:therapeutic use; D007962:Leukocytes / Q000502:physiology; D008297:Male; D051379:Mice; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000209:etiology / Q000517:prevention & control*
chemical_list: D052117:Benzodioxoles; D007529:Isoflavones; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; C543188:methylophiopogonanone A