Proteomics analyses of Xiaopi granules in N‐methyl‐N′‐nitro‐N‐nitrosoguanidine–induced gastric epithelial dysplasia rat model using LC–MS

Abstract

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 0 -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.

The effect of phytochemicals in N-methyl-N-nitro-N-nitroguanidine promoting the occurrence and development of gastric cancer

“…The findings of Cai et al (2019) implied that abnormal glycolysis induced by MNNG in gastric precancerous lesions in rats was relieved by Weipixiao decoction. Peng et al (2022) found that Xiaopi granules ameliorated MNNG mediates gastric epithelial dysplasia by intervening in metabolism, digestion, coagulation, and other related physiological/pathological processes. Dendrobium huoshanense polysaccharides might protect against MNNG-induced injury of gastric mucosa cells mediated by nicotinamide and energy metabolism related pathways ( Xie et al, 2023 ).…”

“…MNNG can induce gastric cancer by regulating inflammation, cell damage, cell differentiation mitochondrial dysfunction, glycolysis pathogenesis and oxidative stress processes ( Cai et al, 2018 ; Zhao et al, 2019a ; Cai et al, 2019 ; Cui et al, 2021 ; Wen et al, 2021 ; Gunes-Bayir et al, 2022 ). MNNG promotes the occurrence and development of gastric cancer by regulating processes such as autophagy, EMT, apoptosis, proliferation, angiogenesis, gastric epithelial dysplasia, malignant transformation and change endogenous metabolites ( Zhao et al, 2019b ; Deng et al, 2019 ; Wu and Hui, 2020 ; Liang et al, 2022a ; Cai et al, 2022 ; Chen et al, 2022 ; Peng et al, 2022 ; Yang et al, 2022 ; Xie et al, 2023 ).Therefore, there is an urgent need to find an effective and low side effect intervention or treatment strategy. In recent years, phytochemicals and active ingredients of herbal medicine have showed excellent application prospects in the prevention and treatment of gastric cancer.…”