Eupatilin protects gastric epithelial cells from oxidative damage and down-regulates genes responsible for the cellular oxidative stress

Purpose. The formulated ethanol extract (DA-9601) of Artemisia asiatica has pronounced anti-inflammatory activities and exhibits cytoprotective effects against gastrointestinal damage. Here we investigated whether eupatilin, a major component of DA-9601, has a property of antioxidant activity and protects gastric epithelial cells from H2O2-induced damage. Methods. The protective effect of eupatilin against H2O2-induced damages was studied in gastric epithelial AGS cells by measuring wound healing, cell proliferation, and cell viability. Global gene expression profiling was obtained by high-density microarray. Results. Hydrogen peroxide significantly delayed epithelial migration in wounded area. In contrast, eupatilin prevented the reduction of epithelial migration induced by H2O2. Eupatilin also ameliorated H2O2-induced actin disruption in AGS cells. Interestingly, treatment with eupatilin dramatically inhibited FeSO4-induced ROS production in a dose-dependent manner. In addition, eupatilin protected cells from FeSO4-induced F-actin disruption. With high-density microarray, we identified dozens of genes whose expressions were up-regulated in H2O2-treated cells. We found that eupatilin reduces the expression of such oxidative-responsible genes as HO-1, PLAUR and TNFRSF10A in H2O2-treated cells. Conclusion. These results suggest that eupatilin acts as a novel antioxidant and may play an important role in DA-9601-mediated effective repair of the gastric mucosa.