Systematic analysis of the mechanism of aged citrus peel (Chenpi) in oral squamous cell carcinoma treatment via network pharmacology, molecular docking and experimental validation.

[Display omitted] • Network pharmacology, molecular docking and in vitro experiments were used to study the role of Chenpi in OSCC. • The key component of Chenpi in OSCC is tangeretin, and the key targets are PIK3R1, ESR1, CDK1. • Molecular docking proved that there is a binding force between the components in the Chenpi and key targets. • Cell experiments demonstrated that tangeretin inhibits OSCC cell growth and regulates the mRNA expression of key targets. Oral squamous cell carcinoma (OSCC) is a malignant cancer and lacks ideal drugs. Aged citrus peel (Chenpi, CP) is an easily available traditional Chinese medicine (TCM) with potential anticancer effects. Network pharmacology were used to investigate the potential mechanisms of CP in OSCC. Tangeretin was the most crucial active ingredient in CP, as shown by the establishment of the component-target-disease network (C-T-D). Protein-protein interaction (PPI) analysis and survival analysis showed that PIK3R1, ESR1, and CDK1 are core genes. Pathway enrichment analysis showed that PI3K-AKT is the top essential pathways. Molecular docking was used to predict the binding of targets and compounds. In vitro experiments showed that tangeretin inhibits cell proliferation, blocks the cell cycle in S phase, induces apoptosis, regulates core gene expression in SCC25 cells, and has lower toxicity to HOK cells. In conclusion, our study lays the foundation for the use of CP in the treatment of OSCC. [ABSTRACT FROM AUTHOR]