Xiangshao Decoction alleviates gastric mucosal injury through NRF2 signaling pathway and reduces neuroinflammation in gastric ulcer rats

Abstract

Background: A type of gastric mucosal injury disease known as gastric ulcer (GU) is clearly connected to the aberrant release of gastric acid. Traditional botanicals have the potential for anti-inflammation, anti-oxidation, and other multitarget therapies, as well as being safe.

Purpose: The purpose of this study was to investigate the potential effects of Xiangshao Decoction (XST) on gastric mucosal injury in GU rats and to explore the possible molecular mechanisms.

Methods: After identifying XST and its components, we established GU rats and cell models by acetic acid and H₂O₂ induction, respectively. SOD and MDA indexes in gastric tissues and GES-1 cells, and the serum levels of BDNF, ALT, and AST were detected with relevant kits, changes of the gastric mucosa were observed and recorded, and gastric tissue pathology was observed by H&E staining. The production of ROS in GES-1 cells was detected by fluorescent probes. Cell transfection techniques were used to silence or overexpress NRF2. The mRNA or protein expressions of NRF2, KEAP1, NQO1, HO-1, SOD2, IL-1β, IL-6, TNF-α, IBA1, GFAP, or γ-H2AX in the gastric tissue, hippocampus, or GES-1 cells were measured via qPCR, Western blot, immunofluorescence staining, or immunohistochemical staining.

Results: The pH of gastric acid, ulcer score, and pathological damage score in GU rats could be reversed by XST administration. Expressions of IL-1β, IL-6, and TNF-α in the gastric mucosal tissues and the hippocampus of GU rats after administration of XST were down. Expressions of NRF2, NQO1, HO-1, SOD2, etc. in the gastric mucosal tissues and BDNF in the hippocampus were up-regulated. The production of ROS and MDA and the expressions of IL-1β, IL-6, TNF-α, and KEAP1 in H₂O₂-induced GES-1 cells were significantly reduced after XST intervention, while the activities of SOD and the expression of NRF2, NQO1, HO-1, and SOD2 were significantly increased, and these could be blocked by silencing NRF2 expression.

Conclusions: XST can improve oxidative stress injury and inflammatory response in GU rats and cell models, and its mechanism is mediated by the NRF2 signaling pathway.

Keywords: Gastric ulcer; Neuroinflammation; Nuclear factor e2-related factor 2; Oxidative stress; Xiangshao Decoction.