Integrated network pharmacology, molecular docking, and experimental validation reveal the antifungal and anti-inflammatory mechanisms of Camellia oleifera seed extracts against oral thrush

Abstract Oral thrush, primarily caused by Candida albicans, is often accompanied by inflammation and pain. Due to rising resistance and side effects of current antifungal treatments, safer and more effective alternatives are needed. This study investigates the antifungal mechanisms of Camellia oleifera seed extracts against oral thrush using network pharmacology, molecular docking, and in vitro validation. UHPLC-Q-TOF-MS identified chemical components in the extracts, selecting those meeting Lipinski’s Rule of Five. Oral thrush-related targets were retrieved from public databases, and a compound-target network was built to identify key targets. Protein-protein interaction (PPI) networks, GO, and KEGG analyses were conducted. Molecular docking assessed interactions between active compounds and core targets. Antifungal efficacy and cytotoxicity were evaluated in vitro. Twenty-three active compounds were identified. Tea saponin showed favorable docking scores to STAT3, a key intracellular mediator of IL-6–driven inflammatory signaling, suggesting potential modulation of the IL-6/STAT3 axis. The extracts inhibited Candida albicans growth and biofilm formation in vitro; however, cytotoxicity toward human gingival fibroblasts was observed at concentrations lower than those required for antifungal efficacy, resulting in a limited therapeutic index. Camellia oleifera seed extracts exhibit antifungal and anti-inflammatory activity against oral thrush in vitro, but their therapeutic window appears narrow under the conditions tested. These findings highlight the potential of the extracts as lead candidates for topical or formulation-optimized antifungal applications, while emphasizing the need for further optimization and in vivo safety evaluation.