Lin Mingbao, Sun Wei, Gong Wan, Zhou Zhiyu, Ding Yasi, Hou Qi
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.
Clinical Laboratory Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
PLoS One. 2015 Apr 21;10(4):e0124558. doi: 10.1371/journal.pone.0124558. eCollection 2015.
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.
甲基麦冬黄酮A（MO-A）是中药麦冬的一种活性高异黄酮，已被证明对脑缺血/再灌注（I/R）损伤具有保护作用，还具有抗炎和抗氧化特性。然而，其在脑I/R损伤中的作用尚不清楚。因此，在本研究中，通过使用大脑中动脉闭塞（MCAO）和再灌注大鼠模型，研究了MO-A对脑I/R损伤的影响。结果表明，MO-A治疗可减少梗死体积和脑水肿，改善神经功能缺损评分，逆转动物体重下降，并延长中风组动物的存活时间。蛋白质免疫印迹法显示，MO-A可抑制基质金属蛋白酶-9（MMP-9），但可恢复紧密连接蛋白3（claudin-3）和紧密连接蛋白5（claudin-5）的表达。此外，通过透射电子显微镜监测体外血脑屏障（BBB）的变化。结果表明，MO-A可显著减轻体外BBB损伤。此外，MO-A在体外可抑制内皮细胞（ECs）中活性氧（ROS）的产生和分化的单核细胞白血病细胞系（THP-1）细胞中MMP-9的释放，并抑制ECs中细胞间黏附分子-1（ICAM-1）和血管细胞黏附分子-1（VCAM-1）的表达以及白细胞/EC黏附。总之，我们的数据表明，MO-A通过调节MMP-9和紧密连接蛋白的表达来减轻BBB破坏，从而对脑I/R损伤具有治疗潜力。
