Objective The ameliorative effects of the ethanol extract of Vicatia thibetica de Boiss. (VTDB) on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced chronic atrophic gastritis (CAG) in rats were investigated, and its mechanism of action was preliminarily explored.

Methods Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was used to analyze the chemical constituents of VTDB. A rat CAG model was established using MNNG induction combined with irregular feeding. Seventy-two healthy male SD rats were randomly divided into six groups: normal control, model, low-dose VTDB (157 mg/kg·d), medium-dose VTDB (314 mg/kg·d), high-dose VTDB (628 mg/kg·d), and positive control (Vatacoenayme) (216 mg/kg·d), with 12 rats in each group. HE staining was used to observe pathological changes in the gastric mucosa of each group. ELISA was performed to measure serum levels of pepsinogen Ⅰ (PGⅠ), pepsinogen Ⅱ (PGⅡ), and inflammatory factors (TNF-α, IL-6, and IL-10). Levels of malondialdehyde (MDA) and superoxide dismutase (SOD) activity in gastric tissues were determined. Western blot was used to measure the expression levels of heme oxygenase-1 (HO-1)/nuclear factor erythroid-2-related factor 2 (Nrf2) and myeloid differentiation primary response protein 88 (MyD88)/protein kinase B (AKT)/phosphatidylinositide 3-kinase (PI3K) signaling pathway proteins in gastric tissues.

Results By comparing retention times, mass spectral fragmentation patterns, and matching with the ESI (±)-MS/MS database, a total of 89 chemical constituents–primarily fatty acids, phenolic acids, and coumarins–were identified in VTDB. HE staining indicated that VTDB partially improved gastric mucosal damage in CAG rats. ELISA showed that, compared with the model group, the VTDB-treated groups had increased serum levels of PGⅠ, PGⅡ, and PGR (PGⅠ/PGⅡ) (P < 0.05) and decreased levels of gastrin 17 (G-17) (P < 0.05). In the low-, medium-, and high-dose groups, serum TNF-α levels decreased, and in the low- and high-dose groups, serum IL-6 secretion decreased (P < 0.05), while serum IL-10 secretion increased in the high-dose group (P < 0.001). In the VTDB medium- and high-dose groups, MDA levels in gastric tissue decreased (P < 0.01), and SOD activity increased in the VTDB low-, medium-, and high-dose groups (P < 0.05). Western blot results showed that HO-1 levels increased in the high-dose VTDB group and Nrf2 levels increased in the low-, medium-, and high-dose VTDB groups (P < 0.001). MyD88 levels decreased in the VTDB low- and high-dose groups, while AKT and PI3K levels decreased in the VTDB medium- and high-dose groups (P < 0.05), indicating that VTDB can modulate the expression of HO-1/Nrf2 and MyD88/AKT/PI3K signaling pathway proteins.

Conclusion VTDB reduces gastric damage and inflammation in CAG rats by inhibiting lipid peroxidation and inflammatory processes through its effects on the HO-1/Nrf2 and MyD88/AKT/PI3K signaling pathways.