Wenweishu Granule Plays a Protective Role against Stress-Induced Gastric Ulcers by Inhibiting the PI3K/AKT Signaling Pathway

Wenweishu (WWS), a traditional gastritis formula, was studied to elucidate its mechanisms in preventing water immersion restraint stress-induced gastric ulcers (GU) in rats. The degree of gastric tissue damage was assessed in experimental rats based on the gastric mucosal ulcer index and pathological observation. The antioxidant properties of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-px) were detected in gastric tissues, along with expression levels of inflammatory factors, such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6. The core components, primary targets, and putative mechanisms of WWS were predicted using network pharmacology and molecular docking and validated via immunohistochemistry and immunoblotting analyses. WWS reduced the ulcer index, increased SOD and GSH-px, and decreased IL-1β, IL-6, TNF-α, and MDA levels. A total of 126 WWS components were identified and associated with 4920 GU-associated targets via network pharmacological analysis. Data from Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed associations of the core targets with multiple pathways, in particular, phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling. Molecular docking analysis confirmed significant docking activity of the main bioactive components with the core targets tumor protein (TP53) and protein kinase Bα (AKT1). Immunohistochemistry and Western blot analyses showed that WWS markedly suppressed phosphorylation levels of Akt and PI3K proteins in gastric tissues. WWS exerts a protective effect on the gastric mucosa by inhibiting the PI3K/Akt pathway, attenuating inflammatory factors and oxidative damage. The collective findings provide a scientific basis for the application of WWS in the management of GU.