Whether wogonin (5,7-dihydroxy-8-methoxyflavone), a flavonoid originated from the root of Scutellaria baicalensis Georgi, which has been shown to have antiinflammatory and antitumor activities in various cell types, possesses a gastric cytoprotective effect was investigated in an ethanol-induced gastric damage model in rats. Ethanol administration alone induced evident gastric damage including gastric hemorrhages and edema, while this gastric damage was significantly attenuated by wogonin pretreatment (30 mg/kg B.W.) 1 hr before ethanol administration. As major protective mechanisms of wogonin on ethanol-induced gastric damage, we found that wogonin showed either antiinflammatory effects through dual actions on arachidonic acid metabolism, i.e., induction of prostaglandin D 2 and suppression of 5S-hydroxyeicosatetraenoic acid (5S-HETE), or preventive induction of profuse apoptosis in the stomach. Conclusively, the flavonoid wogonin could be used as a preventive agent of alcohol-induced gastropathy, whose actions were proven to be strong antiinflammation and apoptosis induction.
A B S T R A C T Background.Helicobacter pylori infection leads to gastric mucosal damage by several mechanisms including the direct effect of virulence factors produced by H. pylori, propagation of inflammation, oxidative stress, DNA damage, and induction of apoptosis. (-)-Epigallocatechin-3-gallate (EGCG), one of the green tea catechins, is known to suppress H. pyloriinduced gastritis through its antioxidative and antibacterial actions. In this study, we evaluated the protective mechanism of EGCG against H. pyloriinduced cytotoxicity in gastric epithelial cells. Materials and Methods. MTT assays and dyeexclusion assays were performed to analyze the effect of EGCG on the viability of gastric epithelial cells. The degree of DNA damage was evaluated by Comet assay and apoptotic DNA fragmentation assay. To investigate the effect of EGCG on H. pylori-induced toll-like receptor 4 (TLR-4) signaling, reverse transcription-polymerase chain reaction and Western blot analysis corresponding to glycosylated TLR-4 were carried out. Lipoxygenase metabolites were measured with reverse-phase, high-performance liquid chromatography.
Our recent studies documented that red ginseng extract (RGE, isolates from steamed and dried Panax ginseng, C.A. Meyer) can inhibit Helicobacter pylori-induced mitogen-activated protein kinase (MAPK) signaling with repressing either nuclear factor (NF)-κB-DNA binding activity or releases of IL-8 and COX-2 in gastric epithelial cells (Dig Dis Sci 50:1218-1227, 2005. We extended the experiment to prove whether RGE influences 5-lipoxygenase (5-LOX) pathway, thereby suppressing the biosynthesis of 5(S)-HETE. The 5-LOX enzyme activities were measured by thin layer chromatography using 14 C-labeled arachidonic acid (AA) and quantified by reverse phase-high performance liquid chromatography in human gastric adenocarcinoma (AGS) cells cocultured with H pylori (ATCC 43504 strain) with or without pretreatment of RGE. Western blotting analyses for MAPK signaling and 5-LOX, reverse transcriptase polymerase chain reaction for interleukin-8, and electrophoretic mobility shift assay for NF-κB-DNA binding were done, respectively. H pylori infection increased exclusively 5-LOX enzyme activity and RGE inhibited H pylori-stimulated 5-LOX activity, resulting in suppression of 5(S)-HETE generations from AA. RGE inactivated c-jun phosphorylation and repressed redox-sensitive transcriptional activation, led to reduced expression of IL-8 and 5-LOX mRNA in gastric mucosal cells, of which action was
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.