Abstract
Background 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 mechanism of intervention of ZJP in chronic atrophic gastritis (CAG) through metabolomics combined with network pharmacology.Materials and methods Potential metabolites and possible pathways for ZJP treatment of CAG were explored using a UPLC-Q-TOF/MS-based metabolomics technique. The key targeting mechanism of ZJP for CAG was explored by combining the analysis with network pharmacology.Results ZJP significantly reduced serum levels of IL-1β, IL-6, IL-10 and iNOS, and improved pathological characteristics. Metabolomic results indicated that the therapeutic effect of ZJP was mainly related to ten metabolites, including 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 potential metabolic markers and key targets of network pharmacology by RT-PCR analysis showed that ZJP significantly down-regulated a series of inflammatory markers, such as MAPK1, PKIA, RB1, SCN5A, RXRA, E2F1, PTGS1, IGF2, ADRB1, ADRA1B, PTGS2, and GABRA1.Conclusion For the first time, a combination of metabolomics and network pharmacology has been used to clarify the therapeutic effects of ZJP on CAG and its relationship to the regulation of multiple metabolic pathways.
Therapeutic effects of Zuojin Pill on Helicobacter pylori-induced chronic atrophic gastritis through JMJD2B/COX-2/VEGF signaling axis