Ammonium glycyrrhizinate protects gastric epithelial cells from hydrogen peroxide-induced cell death

Glycyrrhiza uralensis has a potential for preventing or ameliorating gastric mucosal ulceration. To understand the molecular mechanism about the medicinal effect of G. uralensis, we isolated four single compounds from G. uralensis and one related compound and screened for the cellular protective effect against H₂O2-induced damage in gastric epithelial AGS cells. Interestingly, we found that ammonium glycyrrhizinate (AG) prepared from glycyrrhizin dramatically protects AGS cells from H₂O ₂-induced damage as measured by the integrity of actin cytoskeleton. AG also inhibited FeSO₄-induced reactive oxygen radicals in a dose-dependent manner, suggesting the role for AG as a free radical scavenger. To better understand the protective role of AG at the transcriptional level, we performed genome-wide expression profiling using high-density oligonucleotide microarrays, followed by validation using RT-PCR. Among the 33,096 genes that were screened in the microarray, 936 genes were found to be differentially expressed in a statistically significant manner in the presence or absence of H₂O₂ and AG. Among the 936 genes, 51 genes were differentially expressed at least 3- fold in response to the H₂O ₂ treatment. AG blocked the expression of genes related to apoptotic cell death (GDF15, ATF3, TNFRSF10A, NALP1) or oxidative stress path-ways (HMOX1) which was elevated in response to H₂O₂ treatment, suggesting a potential protective role for AG in oxidative stressinduced cell death. Collectively, current results demonstrate that AG is a novel antioxidant that could be effective for the treatment of gastric diseases related to the oxidative stress-induced mucosal damage.