Protective Role of Quercetin in Chronic Atrophic Gastritis: Modulation of Gastric Mucosal Integrity via the Transforming Growth Factor-beta1/Smads Signaling Pathway.

Objective: This study aimed to elucidate the protective effects of quercetin (Que) on the gastric mucosa in a rat model of chronic atrophic gastritis (CAG), with emphasis on the regulation of the transforming growth factor-beta1 (TGF-β1)/Smads signaling pathway.

Methods: Wistar rats were randomly divided into five groups: control, model, low-dose Que (Que-L), and high-dose Que (Que-H). After 30 days of oral gavage, the rats were euthanized for further analysis. Histopathological changes, gastric function (pH, secretion volume, and pepsin activity), and serum levels of gastrin-17 (G-17), interleukin-17 (IL-17), proliferating cell nuclear antigen (PCNA), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), and growth hormone (GH) were evaluated. The expression levels of PCNA, VEGF, TGF-β1, Smad4, and Smad7 were determined by quantitative real-time PCR (qRT-PCR) and Western blot. Gastric epithelial cells-1 (GES-1) cells were infected with Helicobacter pylori (H. pylori) and treated with Que and the TGF-β1/Smad pathway activator SRI-011381. Cell viability, morphological damage, and TGF-β1/Smads pathway expression were subsequently assessed.

Results: Rats in the model group exhibited significantly increased gastric juice pH, decreased total gastric secretion volume and pepsin activity, elevated serum levels of PCNA, VEGF, and EGF, and reduced levels of GH and G-17 (p < 0.05). In gastric tissues, PCNA, VEGF, Smad4, and TGF-β1 were upregulated, while Smad7 was downregulated (p < 0.05). Que treatment improved gastric function, normalized serum biomarkers, and decreased the expression of PCNA, VEGF, Smad4, and TGF-β1, while upregulating Smad7 (p < 0.05). In H. pylori-infected GES-1 cells, Que suppressed PCNA and VEGF expression, enhanced cell viability, and improved nuclear morphology (p < 0.05). It also downregulated TGF-β1 and Smad4 while restoring Smad7 expression. Pretreatment with SRI-011381 attenuated the protective effects of Que (p < 0.05).

Conclusions: Que alleviates gastric inflammation, improves gastric secretory function, and modulates key molecular markers (PCNA, EGF, VEGF, G-17, and GH), thereby protecting against gastric mucosal injury in CAG rats. These effects are likely mediated through inhibition of the TGF-β1/Smads signaling pathway.