[Ethanol Extract of Vicatia thibetica de Boiss. Improves Chronic Atrophic Gastritis in Rats via the HO-1/Nrf2 and Myd88/AKT/PI3K Signaling Pathways].

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.