This study was designed to determine the protective effect of Rumex Aquaticus Herba extracts containing quercetin-3-β-D-glucuronopyranoside (ECQ) on experimental reflux esophagitis. Reflux esophagitis was induced by surgical procedure. The rats were divided into seven groups, namely normal group, control group, ECQ (1, 3, 10, 30 mg/kg) group and omeprazole (30 mg/kg) group. ECQ and omeprazole groups received intraduodenal administration. The Rats were starved for 24 hours before the experiments, but were freely allowed to drink water. ECQ group attenuated the gross esophagitis significantly compared to that treated with omeprazole in a dose-dependent manner. ECQ decreased the volume of gastric juice and increased the gastric pH, which are similar to those of omeprazole group. In addition, ECQ inhibited the acid output effectively in reflux esophagitis. Significantly increased amounts of malondialdehyde (MDA), myeloperoxidase (MPO) activity and the mucosal depletion of reduced glutathione (GSH) were observed in the reflux esophagitis. ECQ administration attenuated the decrement of the GSH levels and affected the MDA levels and MPO activity. These results suggest that the ECQ has a protective effect which may be attributed to its multiple effects including anti-secretory, anti-oxidative and anti-inflammatory actions on reflux esophagitis in rats.

The Rumex Aquaticus Herba extract containing quercetin-3-β-D-glucuronopyranoside (ECQ) has been reported to exhibit various pharmacological activities, including anti-inflammatory and anti-oxidative effects. This plant has been traditionally used for the treatment of diarrhea, disinfestation, edema and jaundice, and as an antipyretic drug. The aim of the present study was to investigate the ability of ECQ to protect against oxidative damage and to determine its signaling mechanism in AGS cells. The protein expressions of heme oxygenase-1 (HO-1) and nuclear factor-erythroid 2 related factor 2 (Nrf2) were measured by Western blots. Cell viability was measured by MTT assay. Intracellular reactive oxygen species (ROS) levels were measured using 2',7'-dichlorofluorescein diacetate. Glutathione peroxidase levels were measured using kits. The protein expressions of HO-1 and its upstream mediator, Nrf2, increased after ECQ treatment. The HO-1 inhibitor, ZnPP, repressed the protective effect of ECQ on HO-induced cell damage. We found that LY294002, a specific PI3 K/Akt inhibitor, suppressed ECQ-induced HO-1 expression. ECQ significantly attenuated HO-induced cytotoxicity and ROS generation. Also, ECQ enhanced the antioxidant enzyme activities of glutathione peroxidase. These results suggest that ECQ exerts a cytoprotective effect against HO-induced oxidative stress by upregulation of Nrf2/HO-1 via the PI3 K/Akt pathway.

The purposes of this study were to examine the characteristics of Helicobacter pylori and the effect of Rumex Aquaticus Herba extract on the expression of cytokines in H. pylori-infected gastric epithelial cells. Cultured human adenocarcinoma gastric cells (AGS) were infected by H. pylori in RPMI 1640 media. Cell growth was measured by trypan blue assay. Western blot analysis was performed to investigate effect of extract containing Quercetin-3-O-β-d-glucuronopyranoside (ECQ) on the expression of inflammatory factors and the inhibition on cell growth. Furthermore, we compared the inhibitory effects with various combinations of clarithromycin, amoxicillin, omeprazole, and ECQ. The urease test with Christensen's Urea Agar was performed to identify the urease activity of H. pylori and the effect ECQ has on urease activity. When the cells were exposed to H. pylori, the trypan blue assay revealed a decrease in the rate of cell growth. Western blot analysis showed that H. pylori-infected cells had increased levels of degraded IκB-α and inflammatory factors. Pretreatment with ECQ inhibited interleukin expression induced by H. pylori in a dose-dependent manner. A combination of ECQ and antibiotics inhibited cytokine expression more effectively than other treatments. H. pylori displayed significant urease activity. ECQ did not significantly inhibit urease activity. These data suggest that H. pylori infection has cytotoxic effects against AGS cells, and ECQ may inhibit the production of proinflammatory cytokines in H. pylori-infected AGS cells.

Isoform-selective inhibitors of phosphoinositide 3-kinase (PI3K) activation have an anti-inflammatory effect by reducing proinflammatory cytokines. Cultured feline esophageal epithelial cells (EEC) of passages 3~4 were treated with hydrogen peroxide and PIK-75. The cell viability was measured by a MTT incorporation assay. The distribution of PI3K isoforms, p-Akt, IL-1β, and IL-8 was inferred from Western blots. The release of IL-6 was determined by ELISA. The cell morphology was not considerably different from nontreated cells if the cells were pretreated with PIK-75 and treated with 300 μM hydrogen peroxide. The density of p110α of PI3K was increased, but that of other types was not affected after the treatment with hydrogen peroxide. The density of p-Akt, when the cells were exposed to PIK-75 and hydrogen peroxide, was diminished dose dependently more than that of hydrogen peroxide treatment only. The decrease of p-Akt showed an inhibition of PI3K by PIK-75. PIK-75 dose dependently reduced the expression of IL-1β, IL-8, and the level of IL-6 compared with hydrogen peroxide treatment only. These results suggest evidence that p110α mediates esophageal inflammation and that PIK-75 has an anti-inflammatory effect by reducing proinflammatory cytokines on feline esophageal epithelial cultured cells.

The antidepressant fluoxetine (FLX) is a selective serotonin re-uptake inhibitor. It has been reported that fluoxetine can inhibit cancer cell growth and induce apoptosis in various cancer cell lines in additional to treat mental disorders. Moreover, it was described that fluoxetine can inhibit NF-kB signaling in intestinal epithelial cells. Since the expression of NF-kB was up-regulated in gastric adenocarcinoma samples. In this study, the apoptotic effect of fluoxetine in human gastric adenocarcinoma cell line (AGS) was investigated. The cytotoxicity of the AGS in response to fluoxetine was determined by MTT assay. The changes in apoptotic nuclei of AGS cells were stained with DAPI and observed using fluorescence microscopy. The changes in apoptotic-related protein expression were studied by western blotting. The induction of reactive oxygen species (ROS) by fluoxetine was analyzed by using fluorescent probe DCFDA, and fluorescence intensity was detected with a fluorescence microplate reader at maximum excitation and emission wavelengths of 485 nm and 535 nm, respectively. Fluoxetine significantly inhibited the AGS cell proliferation starting at the concentration of 20 uM in a dose-dependent manner. The expression of NF-kB was significantly reduced by the treatment with fluoxetine. The increase of fluorescence intensity and chromatin condensation were observed with DAPI staining. The hallmarks of apoptosis such as the elevated expression of activated caspases, cleavage of poly (ADP-ribose) polymerase (PARP) and the changes in Bcl -2/BAX ratio were seen in fluoxetine-treated cells. The decrease in the ratio of Bcl-2/BAX indicates that fluoxetine may have effect on the mitochondrial membrane potential. The phosphorylation of AKT which can induce cell proliferation was suppressed by fluoxetine treatment. Moreover, the expression of the extrinsic signaling pathway proteins such as TRAIL,DR4, DR5 and FADD were significantly increased by fluoxetine. This study showed that fluoxetine could significantly increase the production of ROS and inhibition of ROS production by NAC and GSH could attenuate the cytotoxic effect of fluoxetine. Moreover, fluoxetine induced apoptosis by decreasing bcl-2/BAX ratio, inhibiting NF-kB and phosphorylation of p-AKT and p-53. Taken together, the apoptotic effect induced by fluoxetine in gastric adenocarcinoma cell line (AGS) was mediated by both extrinsic and intrinsic pathways.