Revealing therapeutic targets and mechanism of baicalin for anti-chronic gastritis using proteomic analysis of the gastric tissue.

ABSTRACT

BACKGROUND: Baicalin (BCL) is a natural compound associated with antioxidant, anti-inflammatory and immunomodulatory activities, among many others. To investigate the therapeutic effect of BCL treatment in ethanol-induced chronic gastritis, we investigated proteomic changes in the gastric tissue to elucidate the therapeutic targets of BCL in chronic gastritis using tandem mass tag (TMT)-based quantitative proteomics. METHODS: Sprague-Dawley (SD) rats received 8.7 ml/kg body weight of 56% ethanol intragastrically, which induced chronic gastritis model. Then, BCL (50 mg/kg) or omeprazole (20 mg/kg) was orally administered for 7 days to treat the induced chronic gastritis. After sacrifice, the total protein of the gastric antrum was determined. In addition, a tandem tag labelling for relative and absolute quantification (TMT)-based liquid chromatography with tandem mass spectrometry analysis was performed on the sample to identify differentially expressed proteins (DEPs) between therapy and model groups. Furthermore, the potential protein targets, signalling pathways and protein-protein interaction (PPI) network were analysed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Finally, some potential targets were validated using Western blotting. RESULTS: A total of 4,452 proteins were identified and quantified in the gastric antrum tissue of SD rats using TMT-based quantitative proteomics. Of these, 107 DEPs, including 44 upregulated and 63 downregulated proteins, were discovered in the BCL-treated group compared with the untreated group with ethanol-induced gastritis, of these were 33 callback proteins. Biological information analysis demonstrated that the selected differential proteins were involved in the enriched pathways, including MAPK, PI3K-Akt and NF-κB. Furthermore, the expression of TPM2, GIMAP4, ICAM-1 and Mpc1 was validated using Western blotting, which was consistent with the proteomics results. The study results confirmed the reliability of the proteomic analysis. Additionally, BCL could decrease the production of interleukin (IL)-2, IL-8 and tumour necrosis factor-α while increasing the expression of epidermal growth factor and B-cell lymphoma-2. Notably, PPI network analysis revealed widespread interactions mediated by BCL. CONCLUSIONS: We investigated the effects and potential mechanism of BCL in chronic gastritis. Proteomic technology was used to explore BCL-affected proteins and some signalling pathways. The results may provide important insights into discovering potential target proteins for treating chronic gastritis.