Albizzia chinensis(Osbeck)Merr extract YS ameliorates ethanol-induced acute gastric ulcer injury in rats by regulating NRF2 signaling pathwayOA

Background:Around the world,there is a high incidence of gastric ulcers.YS,an extract from the Chinese herb Albizzia chinensis(Osbeck)Merr,has potential therapeutic applications for gastrointestinal diseases.Here we elucidated the protective effect and underlying mechanism of action of YS on gastric ulcer in rats injured by ethanol.Methods:The ethanol-i nduced gastric ulcer rat model was used to assess the protective effect of YS.A pathological examination of gastric tissue was performed by H&E staining.GES-1 cells damaged by hydrogen peroxide were used to simulate oxidative damage in gastric mucosal epithelial cells.Endogenous NRF2 was knocked down using small interfering RNA.Immunoprecipitation was used to detect ubiquitination of NRF2.Co-i mmunoprecipitation was used to detect the NRF2-Keap1 interaction.Results:YS(10 and 30 mg/kg,i.g.)significantly reduced the ulcer index,decreased MDA level,and increased SOD and GSH levels in gastric tissues damaged by ethanol.YS promoted NRF2 translocation from cytoplasm to nucleus and enhanced the NQO1 and HO-1 expression levels in injured rat gastric tissue.In addition,YS regulated NQO1 and HO-1 via NRF2 in H_(2)O_(2)-i nduced oxidative injured GES-1 cells.Further studies on the underlying mechanism indicated that YS reduced the interaction between NRF2 and Keap1 and decreased ubiquitylation of NRF2,thereby increasing its stability and expression of downstream factors.NRF2 knockdown abolished the effect of YS on MDA and SOD in GES-1 cells treated with H_(2)O_(2).Conclusion:YS reduced the NRF2-Keap1 interaction,promoting NRF2 translocation into the nucleus,which increasing the transcription and translation of NQO1 and HO-1 and improved the antioxidant capacity of rat stomach.