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 H₂O ₂-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 H₂O ₂-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 FeSO ₄-induced F-actin disruption. With high-density microarray, we identified dozens of genes whose expressions were up-regulated in H ₂O₂-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.