Ammonium Glycyrrhizinate Protects Gastric Epithelial Cells from Hydrogen Peroxide-Induced Cell Death

Abstract

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 H(2)O(2)-induced damage in gastric epithelial AGS cells. Interestingly, we found that ammonium glycyrrhizinate (AG) prepared from glycyrrhizin dramatically protects AGS cells from H(2)O(2)-induced damage as measured by the integrity of actin cytoskeleton. AG also inhibited FeSO(4)-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 H(2)O(2) and AG. Among the 936 genes, 51 genes were differentially expressed at least 3-fold in response to the H(2)O(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 H(2)O(2) treatment, suggesting a potential protective role for AG in oxidative stress-induced 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.

Radical scavenging ability of glycyrrhizin

“…9e11 Gly acts as a radical scavenger in biological systems, such as ischemiaereperfusion injury, 12,13 macrophage-like cells, 14 and gastric epithelial cells. 15 However, conflicting results have been reported regarding whether Gly itself scavenges radicals. Nagai et al reported that Gly had a potent hydroxyl radical trapping action, but did not trap superoxide anion radicals or 1,1-diphenyl-2picrylhydrazyl (DPPH).…”

Pharmacological Effects ofGlycyrrhizaspp. and Its Bioactive Constituents: Update and Review

“…Ammonium glycyrrhizinate, prepared from glycyrrhizin, could protect gastric epithelial cells from H 2 O 2 -induced damage because it blocked the expression of genes related to apoptotic cell death (GDF15, ATF3, TNFRSF10A, and NALP1) or oxidative stress pathways (HMOX1) during damage induced by exposure to H 2 O 2 (Oh et al, 2009).…”

Effect of ammonium glycyrrhizinate on haloperidol- and reserpine- induced neurobehavioral alterations in experimental paradigms

“…AG may directly scavenge ROS generated from hydrogen peroxide. It was also reported that AG blocked the expression of genes related to apoptotic cell death or oxidative stress pathways which was elevated in response to hydrogen peroxide treatment (Oh et al 2009). …”

“…Its antiradical activity is reported to be responsible for its antiinflammatory action (Oh et al 2009;Rackova et al 2007;Yim et al 2007). However, the effect of AG against chemically induced depletion of DA and related biochemical parameters associated with signs and symptoms of PD and drug-induced extrapyramidal side effects or symptoms remains uncertain.…”