NETWORK PHARMACOLOGY INTEGRATED WITH MOLECULAR DOCKING REVEALS THE MULTI-TARGET MECHANISM OF IPOMOEA BATATAS AGAINST OROPHARYNGEAL CANCER

Abstract

Oropharyngeal cancer (OC) is a rising subtype of head and neck squamous cell carcinoma driven by tobacco, alcohol and human papillomavirus infection, and its management remains constrained by treatment-related toxicity and acquired resistance to conventional chemotherapy and radiotherapy. Plant-derived phytochemicals with polypharmacological profiles are increasingly explored as complementary anticancer agents, yet the mechanistic basis of many ethnomedicinal species remains undefined. Ipomoea batatas (sweet potato), a widely consumed tuber rich in phenolic acids, flavonoids and coumarins, has documented antioxidant, anti-inflammatory and antiproliferative activity, but its molecular targets in oropharyngeal cancer have not been systematically mapped. Here we used an integrated network pharmacology and molecular docking strategy to decipher the multi-target mechanism of I. batatas against oropharyngeal cancer. Phytochemicals were retrieved from the IMPPAT database and their putative human protein targets were predicted using SwissTargetPrediction; disease-associated genes were obtained from GeneCards. Intersection of 473 phytochemical targets with 418 oropharyngeal-cancer-associated genes yielded 74 shared targets, which were mapped onto a protein–protein interaction network using STRING and Cytoscape. CytoHubba prioritised ten hub genes-CTNNB1, STAT3, BCL2, IL6, CCND1, MMP9, TNF, SRC, ESR1 and AKT1-with CTNNB1 (β-catenin) ranking highest. Gene Ontology and KEGG analyses implicated regulation of smooth-muscle-cell proliferation, gland development, the interleukin-6 receptor complex and nitric-oxide synthase regulatory activity, alongside enrichment of the prolactin signalling pathway, endocrine resistance, AGE–RAGE signalling and pathways in cancer. Molecular docking of the coumarin scopoletin against the crystal structure of CTNNB1 (PDB: 8Y0G) produced a binding energy of −5.47 kcal/mol (ligand efficiency, −0.39 kcal/mol). These findings provide systems-level and structural evidence that I. batatas phytochemicals, particularly scopoletin, may exert anti-oropharyngeal-cancer activity through modulation of the CTNNB1/Wnt signalling axis, offering a mechanistic rationale and candidate lead for future experimental validation.