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

• Published in: Animal models and experimental medicine Vol. 7; no. 3; pp. 275 - 282
• Main Authors: Tang, Bo, Li, Liangning, Yu, Yuanzhi, Wang, Guibin, Ma, Shuanggang, Yu, Shishan, Zhang, Jianjun
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01-06-2024; John Wiley and Sons Inc; Wiley
• Subjects: Alcohol use; Animals; Antibodies; Antioxidants; antioxidative; Cytoplasm; Drug dosages; Epithelial cells; Ethanol; Gastric mucosa; Gastric Mucosa - drug effects; Gastric Mucosa - injuries; Gastric Mucosa - metabolism; gastric ulcer; Gastrointestinal diseases; Herbal medicine; Hydrogen peroxide; Immunoprecipitation; Kelch-Like ECH-Associated Protein 1 - metabolism; Laboratory animals; Male; Neutrophils; NF-E2-Related Factor 2 - metabolism; NRF2; NRF2 protein; Original; Oxidative stress; Plant Extracts - pharmacology; Plant Extracts - therapeutic use; Rats; Rats, Sprague-Dawley; Signal transduction; Signal Transduction - drug effects; siRNA; Statistical analysis; Stomach Ulcer - chemically induced; Stomach Ulcer - metabolism; Themed Section: Traditional Chinese Medicines and Natural Medicines Research; Therapeutic applications; Ubiquitin; Ubiquitination; Ulcers; Beijing China; China; YS; antioxidative; NRF2; gastric ulcer; ethanol
• ISSN: 2576-2095; 2096-5451; 2576-2095
• DOI: 10.1002/ame2.12401

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‐induced 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‐immunoprecipitation 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 H2O2‐induced 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 H2O2.
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.
YS, extraction from Chinese herb Albizzia chinensis (Osbeck) Merr, has potential therapeutic applications for gastrointestinal diseases, which has been patented. Here we elucidated the protective effect and underling action mechanism of YS on gastric ulcer in rats injured by ethanol. YS (10 and 30 mg/kg, i.g.) significantly reduced the ulcer index and histopathological injury, decreased MDA level, 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 level in injured rat gastric tissue. In addition, YS regulated NQO1 and HO‐1 via NRF2 in H2O2‐induced oxidative injured GES‐1 cells. Further studies on the underlying mechanism indicated that YS reduced the NRF2 and Keap1 interaction, decreased ubiquitylation of NRF2, thereby increasing its stability and downstream factors expression. NRF2 knockdown abolished the effect of YS on MDA and SOD in GES‐1 cells treated by H2O2. Its gastric protective effect is attributed to YS reducing NRF2‐Keap1 interaction, promoting NRF2 translocation into the nucleus, increasing the transcription and translation of NQO1 and HO‐1, improving the antioxidant capacity of rat stomach.