This study aimed to elucidate the therapeutic mechanisms of Sancao Yuyang Decoction (SCYYD) in managing oral mucositis (OM) through a combination of computational and experimental approaches.Bioactive compounds in SCYYD and their potential molecular targets, along with OM-associated targets, were collected from public databases. Protein–protein interaction (PPI) networks, Gene Ontology (GO), and KEGG pathway analyses were employed to identify core targets and signaling pathways involved in SCYYD’s effects. Networks linking ingredients, targets, and disease pathways were constructed. Molecular docking simulations were performed to evaluate the interactions between major compounds and key protein targets. The predictions were further validated using in vivo experiments in OM rat models.A total of 119 active compounds and 186 putative targets were identified. Bioinformatic analyses highlighted five principal compounds and ten core protein targets. GO and KEGG enrichment analyses suggested that SCYYD modulates multiple biological pathways, including HIF-1 and Ras signaling, to exert therapeutic effects. Molecular docking confirmed strong binding affinities of the main compounds to critical targets. In vivo studies demonstrated that SCYYD reduced inflammatory markers, accelerated mucosal healing, decreased the expression of SRC, HSP90AA1, STAT3, HIF1α, mTOR, TLR4, and MMP9, and increased ESR1 levels in OM rats.This integrative study reveals that SCYYD acts through multiple compounds and targets to mitigate OM, combining computational predictions with experimental evidence, and provides mechanistic insights for its pharmacological application.
