Proteomics analyses of Xiaopi granules in N-methyl-N'-nitro-N-nitrosoguanidine-induced gastric epithelial dysplasia rat model using LC-MS.

Xiaopi granules have been shown to ameliorate gastric epithelial dysplasia in patients. However, the therapeutic mechanism is unclear. Herein, the proteomics method was applied to identify the differentially expressed proteins and related pathways. Sixty male Sprague-Dawley rats were randomly divided into four groups: control (C group, n = 10), model (M group), Xiaopi granules (X group), and vitacoenzyme (V group). The rat gastric epithelial dysplasia model was established by intragastrically administering N-methyl-N'-nitro-N-nitrosoguanidine and ranitidine and by orally administering 0.05% ammonia solution. After 12 weeks, the stomach tissue was analyzed by hematoxylin and eosin staining and proteomics analyses. Western-blot analysis was applied to further validate the proteomics results. Compared to the M group, levels of 326 and 350 proteins were altered significantly in the X and V groups (1.5-fold, p < 0.05), which were significantly enriched in digestion, metabolism, coagulation, and cell apoptosis. CELA2A, GHRL, NDUFB9, and PGC were significantly upregulated (p < 0.0001), whereas CLCA1, PLG, and DAC2 were downregulated (p < 0.001 or 0.0001) in the M group vs. the C group. The change in these proteins could be reversed after the treatment of Xiaopi granules or vitacoenzyme tablets. Xiaopi granules ameliorated gastric epithelial dysplasia by intervening in digestion, metabolism, blood coagulation, cell apoptosis, and other related pathways.