Network pharmacology study to reveal active compounds of Fructus Cnidii against oral cancer by regulating the inflammatory microenvironment.

Fructus Cnidii (FC) has a variety of biological activities, including anti-tumor, anti-inflammatory, anti-bacterial, etc. Here, we aim to elucidate the mechanisms underlying the therapeutic effects of FC in treating oral squamous cell carcinoma (OSCC). Network pharmacology was used to investigate the anti-OSCC mechanism of FC. First, a series of databases were used to screen the active phytochemical targets and anti-OSCC targets. Then, the gene ontology and kyoto encyclopedia of genes and genomes pathways were analyzed to predict possible mechanisms. Molecular docking analysis explore core targets-phytochemicals interactions. CCK8 and western blot were carried on verifying the mechanism. In this study, Cytoscape software 3.9.0 identified 9 active ingredient targets and 38 core protein targets. Then, the gene ontology enrichment indicated that FC may play an important role by influencing the inflammatory response. Kyoto encyclopedia of genes and genomes pathway analysis showed that the main anti-OSCC pathways was the tumor pathway. Molecular docking studies revealed that imperatorin, a principal bioactive phytochemical derived from FC, exhibited a strong binding affinity with the key targets prostaglandin G/H synthase 2 and nitric oxide synthase 2. CCK8 and western blot analyses demonstrated that imperatorin reduces the expression of nitric oxide and suppresses the phosphorylation of c-Jun N-terminal kinase within the mitogen-activated protein kinase signaling pathway. Our findings lay a foundation for the development of anti-OSCC drugs from FC.