Department of Life and Nanopharmaceutical Science, Kyung Hee University, 1 Hoegi-dong, Dongdaemoon-ku, Seoul 130-701, Republic of Korea.
Eur J Pharmacol. 2012 Aug 15;689(1-3):104-10. doi: 10.1016/j.ejphar.2012.05.042. Epub 2012 Jun 7.
Eupatilin, a pharmacologically active flavone derived from the Artemisia plant species, has been reported to have anti-oxidant, anti-inflammatory, anti-allergic, and anti-tumor activities. In the present study, we investigated whether eupatilin exhibits neuroprotective activities against ischemia/reperfusion-induced delayed neuronal injury in mice. Transient global cerebral ischemia was induced in mice by bilateral common carotid artery occlusion (BCCAO) for 15 min followed by reperfusion for 4 days. Eupatilin (1, 3, or 10 mg/kg, p.o.) was administered immediately after the reperfusion. Histochemical studies showed that eupatilin (10 mg/kg) increased the number of viable cells detected by Nissl staining and decreased the number of degenerating neuronal cells detected by Fluoro-Jade B staining in the hippocampal CA1 region. Western blotting indicated that eupatilin further increased the level of Akt phosphorylation at 8h after BCCAO. Furthermore, wortmannin, a phosphatidylinositol 3-kinase inhibitor, attenuated the eupatilin-induced increase of Akt phosphorylation. In addition, wortmannin completely reversed the eupatilin-induced neuroprotective effects observed at 4 days after reperfusion. These findings suggest that eupatilin is a promising therapeutic agent against global cerebral ischemia-induced neuronal damage and that its neuroprotective effects may be mediated in part by increased Akt phosphorylation.
从蒿属植物中提取的具有药理活性的黄酮类化合物，白杨素具有抗氧化、抗炎、抗过敏和抗肿瘤活性。在本研究中，我们研究了白杨素是否对小鼠缺血/再灌注诱导的迟发性神经元损伤具有神经保护作用。通过双侧颈总动脉闭塞（BCCAO）诱导小鼠短暂性全脑缺血 15 分钟，然后再灌注 4 天。再灌注后立即给予白杨素（1、3 或 10mg/kg，po）。组织化学研究表明，白杨素（10mg/kg）增加了尼氏染色检测到的存活细胞数量，并减少了氟罗-杰德 B 染色检测到的海马 CA1 区变性神经元细胞的数量。Western blot 分析表明，BCCAO 后 8 小时，白杨素进一步增加了 Akt 磷酸化水平。此外，磷脂酰肌醇 3-激酶抑制剂wortmannin 减弱了白杨素诱导的 Akt 磷酸化增加。此外，wortmannin 完全逆转了再灌注 4 天后观察到的白杨素诱导的神经保护作用。这些发现表明，白杨素是一种有前途的治疗全脑缺血诱导神经元损伤的药物，其神经保护作用部分可能是通过增加 Akt 磷酸化介导的。
