Abstract
Zuojin Pill (ZJP) is widely used for the treatment of gastrointestinal diseases, while its specific mechanism has not been systematically investigated. The aim of this study was to explore the therapeutic effects and potential mechanism of ZJP in chronic atrophic gastritis (CAG) through UPLC-Q-TOF/MS-based metabolomics combined with network pharmacology. ZJP and omeprazole significantly reduce contents of IL-1β, IL-6, IL-10, and iNOS and improve pathological characteristics. Metabolomic results indicated that the therapeutic effects of ZJP were mainly related to ten metabolites, namely, choline, L-threonine, hydroxypyruvic acid, creatine, taurine, succinic acid, cis-aconitic acid, citric acid, succinic acid semialdehyde, and uric acid. Pathway analysis showed that the treatment of CAG by ZJP was associated with taurine and hypotaurine metabolism; glyoxylate and dicarboxylate metabolism; glycine, serine, and threonine metabolism; glycerophospholipid metabolism; citrate cycle (TCA cycle), alanine, aspartate, and glutamate metabolism; butanoate metabolism; and purine metabolism. Validation of metabolic markers and key targets of network pharmacology through RT-PCR analysis showed that ZJP significantly downregulated a series of inflammatory markers, such as MAPK1, PKIA, RB1, SCN5A, RXRA, E2F1, PTGS1, IGF2, ADRB1, ADRA1B, PTGS2, and GABRA1. This study was the first to use a combination of metabolomics and network pharmacology to clarify the therapeutic effects of ZJP on CAG and the regulation of multiple metabolic pathways.
Highlights
In 1993, the World Health Organization’s International Agency for Research and Cancer (IARC) defined Helicobacter pylori (H. pylori) as a type 1 carcinogen
E Zuojin Pill (ZJP) and omeprazole groups were effective in improving gastric mucosal lesions, glandular loss, and reducing inflammatory infiltration
Serum levels of IL-1β, IL-6, IL-10, and iNOS were significantly increased in the model group compared with the control group (P < 0.01). e serum contents of IL-1β, IL-6, IL-10, and iNOS were decreased after ZJP and omeprazole administration
Summary
In 1993, the World Health Organization’s International Agency for Research and Cancer (IARC) defined Helicobacter pylori (H. pylori) as a type 1 carcinogen. Modern analytical technologies include nuclear magnetic resonance (NMR), gas chromatography-mass spectrometry (GC-MS), and liquid chromatography-mass spectrometry (LC-MS), combined with multivariate data analysis, such as principal component analysis (PCA), partial least squares discriminate analysis (PLS-DA), and orthogonal projection to latent structures-discriminant analysis (OPLS-DA) [12] Among these methods, ultrahigh performance liquid chromatography with quadrupole time-of-flight (UPLC-Q-TOF) has the advantages of high selectivity, resolution, and accuracy, which is suitable for traditional Chinese medicine (TCM) [13]. Metabolomics combined with network pharmacology has been successfully used to explore the interactions between TCM and disease targets, providing an important direction for the study of therapeutic mechanisms of TCM. UPLC-Q-TOF/MS serum metabolomics and urine metabolomics were used to determine the changes of endogenous metabolites, combined with network pharmacology to screen relevant targets and to clarify possible biomarkers and potential metabolic pathways for ZJP treatment of CAG
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