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Eupatilin inhibits H(2)O(2)-induced apoptotic cell death through inhibition of mitogen-activated protein kinases and nuclear factor-kappaB.

Abstract
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.
AuthorsSoyoung Lee, Myeungsu Lee, Sang-Hyun Kim
JournalFood and chemical toxicology : an international journal published for the British Industrial Biological Research Association (Food Chem Toxicol) Vol. 46 Issue 8 Pg. 2865-70 (Aug 2008) ISSN: 0278-6915 [Print] England
PMID18603343 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Flavonoids
  • NF-kappa B
  • Nuclear Proteins
  • Oxidants
  • Tetrazolium Salts
  • Thiazoles
  • thiazolyl blue
  • eupatilin
  • Hydrogen Peroxide
  • Mitogen-Activated Protein Kinases
  • Caspase 3
Topics
  • Apoptosis (drug effects)
  • Artemisia (chemistry)
  • Blotting, Western
  • Caspase 3 (metabolism)
  • Cell Line
  • Electrophoretic Mobility Shift Assay
  • Epithelial Cells (drug effects)
  • Flavonoids (pharmacology)
  • Flow Cytometry
  • Gastric Mucosa (cytology, drug effects)
  • Humans
  • Hydrogen Peroxide (antagonists & inhibitors, toxicity)
  • Mitogen-Activated Protein Kinases (antagonists & inhibitors)
  • NF-kappa B (antagonists & inhibitors)
  • Necrosis
  • Nuclear Proteins (metabolism)
  • Oxidants (toxicity)
  • Tetrazolium Salts
  • Thiazoles

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