Eupatilin inhibits H(2)O(2)-induced apoptotic cell death through inhibition of mitogen-activated protein kinases and nuclear factor-kappaB.
Eupatilin (5,7-dihydroxy-3',4',6-trimethoxyflavone), an extract from Artemisia asiatica Nakai, is a flavonoid of pharmacologically active ingredients. Eupatilin is known to possess anti-cancer, anti-inflammatory, and anti-oxidative activity. Recently, eupatilin has been reported to be effective in producing gastric mucosal as an anti-gastritis agents. However, the mechanism of protective action is still unknown. We studied cytoprotective actions of eupatilin on H(2)O(2)-induced cell death and its possible mechanisms of action in human gastric (AGS) cells. Eupatilin dose-dependently inhibited H(2)O(2)-induced apoptosis as indicated by co-staining with Annexin V and propidium iodide. Hydrogen peroxide provoked phosphorylation of extracellular regulated kinase (ERK) and c-Jun NH(2)-terminal kinase (JNK), and activation of nuclear factor-kappaB (NF-kappaB). On the contrary, eupatilin decreased H(2)O(2)-induced activation of ERK, JNK and NF-kappaB. In addition, treatment of specific inhibitors for ERK, JNK, and NF-kappaB attenuated H(2)O(2)-induced apoptosis. Co-treatment of inhibitors and eupatilin was more effective in decreasing H(2)O(2)-induced apoptosis. Taken together, we suggest that eupatilin inhibits H(2)O(2)-induced apoptosis through the inhibition ERK, JNK, and NF-kappaB.
Lee
Soyoung
S
CMRI, Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu 700-422, Republic of Korea.
Lee
Myeungsu
M
Kim
Sang-Hyun
SH
D017209:Apoptosis / Q000187:drug effects*; D019306:Artemisia / Q000737:chemistry; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D024202:Electrophoretic Mobility Shift Assay; D004847:Epithelial Cells / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology*; D005434:Flow Cytometry; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D009336:Necrosis; D009687:Nuclear Proteins / Q000378:metabolism; D016877:Oxidants / Q000633:toxicity*; D013778:Tetrazolium Salts; D013844:Thiazoles
D005419:Flavonoids; D016328:NF-kappa B; D009687:Nuclear Proteins; D016877:Oxidants; D013778:Tetrazolium Salts; D013844:Thiazoles; C045325:eupatilin; D006861:Hydrogen Peroxide; D020928:Mitogen-Activated Protein Kinases; D053148:Caspase 3; C022616:thiazolyl blue