Anti-acute gastric ulcer resistance of Aurantii Fructus Immaturus juice processing Atractylodis Macrocephalae Rhizoma by regulating PTGS2, MAPK1, and KDR targets based on metabolomics and integrated network pharmacology analysis

Abstract

Abstract Background Currently, traditional methods of treating acute gastric ulcer (AGU) have many drawbacks, necessitating an alternative therapy with fewer adverse effects. Atractylodis Macrocephalae Rhizoma (BZ) is known for strengthening the spleen and harmonizing the stomach. BZ processed with Aurantii Fructus Immaturus juice (ZSZBZ), a classic decoction since the Han Dynasty, can enhance the efficacy of BZ. However, the key active components and targets of action of ZSZBZ remain undiscovered. Aim of the study This study aimed to investigate the bioactive chemical constituents of ZSZBZ against AGU and their possible mechanisms of action, elucidating the scientific content of ZSZBZ processing. Materials and methods Initially, we examined rat stomach histopathology and conducted ELISA for oxidative stress and inflammation. Subsequently, we investigated underlying mechanisms using metabolomics. Further analysis of potent components and key targets in ZSZBZ was conducted through liquid chromatography-mass spectrometry analysis combined with network pharmacology. Finally, key targets were analyzed by Western blot. Results ZSZBZ improved gastric histopathology, reversing high alcohol-induced oxidative stress (SOD, CAT) and inflammatory level (TNF-α, IL-6) disorders. This is associated with ZSZBZ’s regulation of amino acid metabolism, energy metabolism, and inflammatory response-related metabolic pathways, along with key targets PTGS2, MAPK1, and KDR. The significant increase in potency of ZSZBZ may be attributed to elevated levels of naringenin, hesperidin, hesperidin, and rhamnoceroside after concoction. Conclusions Combining metabolomics and network pharmacology, this study elucidated that ZSZBZ enhanced gastroprotection by modulating amino acid metabolism, antioxidant, and inflammation-related targets and pathways, providing insights into the bioactive compounds and potential mechanisms of herbal concoctions.