The neuroprotective effect of eupatilin against ischemia/reperfusion-induced delayed neuronal damage in mice.
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.
Department of Life and Nanopharmaceutical Science, Kyung Hee University, 1 Hoegi-dong, Dongdaemoon-ku, Seoul 130-701, Republic of Korea.
Mudan
M
Cai
Phuong-Thuy T
PT
Phan
Jin Gyu
JG
Hong
Dong Hyun
DH
Kim
Jong Min
JM
Kim
Se Jin
SJ
Park
Xiaotong
X
Liu
Jeong Eun
JE
Han
Haeil
H
Park
Ji Woong
JW
Choi
Jong Hoon
JH
Ryu
D000818:Animals; D002545:Brain Ischemia / Q000473:pathology* / Q000517:prevention & control; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D005419:Flavonoids / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015427:Reperfusion Injury / Q000473:pathology* / Q000517:prevention & control*; D013997:Time Factors
D004365:Drugs, Chinese Herbal; D005419:Flavonoids; D018696:Neuroprotective Agents; C045325:eupatilin