Objective To investigate the potential mechanism and effects of Yunyujian for the treatment of oral ulcers. Methods (1) The active components and effect targets of Traditional Chinese Medicine components of Yunyujian were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and BATMAN⁃TCM database. Oral ulcer⁃related targets were retrieved from the GeneCards®, OMIM®, DrugBank, and PharmGKB databases. Intersection targets between the two were identified. A drug⁃component⁃target network was constructed using Cytoscape software to screen for key active components. A protein⁃protein interaction (PPI) network of the intersection targets was constructed using the STRING database to identify core targets. Gene Ontology functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed using the Metascape database. Molecular docking validation was carried out using AutoDock Vina tool. (2) Forty male SD rats were randomly divided into control, model, and high⁃, medium⁃ and low⁃dose Yunyujian groups, with 8 rats in each group. Except for the control group, oral ulcer models were established in the remaining groups by applying 50% glacial acetic acid to the labial mucosa over the alveolar bone of the mandibular incisors. From day 2 of the experiment, rats in the high⁃, medium⁃, and low⁃dose Yunyujian groups received intragastric administration of 12.8 g/kg, 6.4 g/kg, and 3.2 g/kg Yunyujian Decoction, respectively, while the control and model groups received intragastric administration of an equal volume of normal saline, for 7 consecutive days. Oral ulcer areas were measured on days 3, 5, and 7 of experiment. On day 8 of experiment, histopathological changes in ulcer tissues were observed using HE staining, and serum levels of tumor necrosis factor α (TNF⁃α), interleukin (IL)⁃1β, and IL⁃6 were measured by ELISA. Results (1) A total of 51 active components of Traditional Chinese Medicine components and 440 effect targets of Traditional Chinese Medicine were identified for Yunyujian, along with 2613 oral ulcer⁃related targets, yielding 241 intersection targets. Key active components of Yunyujian for treating oral ulcer included quercetin, stigmasterol, kaempferol, and wogonin. Core targets included tumor suppressor p53, RAC⁃α serine/threonine⁃protein kinase 1, and Jun proto⁃oncogene. The intersection targets were mainly involved in biological processes such as response to hormones and response to exogenous substances, in cellular components including membrane rafts, vesicle lumen, and presynaptic membrane, and in molecular functions such as oxidoreductase activity and transcription factor binding, as well as in signaling pathways including the advanced glycation end⁃product⁃receptor for advanced glycation end⁃product pathway in diabetic complications, the phosphatidylinositol 3⁃kinase/protein kinase B signaling pathway, and the nuclear factor κB signaling pathway. Molecular docking results revealed that the binding energies between most key active components and core target proteins were ≤−5 kcal/mol. (2) On days 5 and 7 of experiment, oral ulcer areas in the high⁃ and medium⁃dose Yunyujian groups were smaller than those in the model group (P<0.05). Serum levels of TNF⁃α, IL⁃1β, and IL⁃6 were lower in different⁃dose Yunyujian groups compared with the model group (P<0.05). HE staining results indicated that the model group exhibited disrupted oral mucosal structure, epithelial exfoliation, and inflammatory cell infiltration in rats, whereas the different⁃dose Yunyujian groups interpreted markedly milder pathological changes in oral ulcer tissue as compared with the model group. Conclusion Yunyujian is effective in treating oral ulcers and exhibits the characteristics of multi⁃component, multi⁃target, and multi⁃pathway action.

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