Sanhuang xiexin decoction ameliorates gastric ulcers by activating EGFR/PI3K/AKT pathway based on "drug-target-metabolite" network.

The classical herbal formulation, Sanhuang Xiexin Decoction (SHXD), has been widely used to treat peptic ulcers. However, its specific therapeutic mechanism in gastric ulcer (GU) remains unclear and warrants deeper exploration. This research sought to shed light on therapeutic action of SHXD against GU based on "drug-target-metabolite" network. The main components of SHXD in rats blood were identified by UPLC-MS. Next, network pharmacology as well as metabolomics were employed to pinpoint potential targets of SHXD for GU treatment based on its components. The bioinformatics results were subsequently validated through in vivo experiments. Therapeutic efficacy was evaluated by the ulcer index, pathological scores, oxidative stress, and inflammatory responses. Using AB-PAS staining and immunohistochemical assays to detect gastric barrier function. Western blotting and RT-qPCR were performed on gastric tissue to further investigate mechanisms of SHXD for GU. Finally, the mechanism was identified by molecular docking to verify the binding stability of the active components and key targets. Twenty-two kinds of blood-absorbed components of SHXD in the treatment of GU were identified. Then, the analysis via network pharmacology and metabolomics revealed anti-GU impact of SHXD through modulation of EGFR and PIK3CA critical targets. SHXD could upregulate the core target EGFR, subsequently triggering PI3K/AKT pathway, thereby encouraging epithelial proliferation with inhibiting apoptosis. SHXD demonstrates significant efficacy in reducing GU symptoms. These findings offer fresh perspectives on complex mechanisms of TCM treating GU, highlighting its ability to target multiple pathways simultaneously.