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.