Systems Pharmacology and Molecular Docking Investigation of Zingerone and Ellagic Acid as Potential Therapeutics for Oral Carcinogenesis

Abstract

Oral carcinogenesis is a complex multistep pathological process that includes oxidative stress, chronic inflammation, aberrant cell proliferation, apoptosis resistance, angiogenesis, and metastatic development. Despite advancements in chemotherapy and targeted medicines, oral cancer treatment remains difficult due to systemic toxicity, drug resistance, and a poor prognosis. As a result, naturally occurring phytochemicals with multitarget therapeutic potential have received significant interest in anticancer research. The current study sought to assess the synergistic therapeutic potential of Zingerone and Ellagic Acid against oral carcinogenesis by integrated computational techniques. A network pharmacology analysis was used to identify common molecular targets linked with oral cancer, followed by protein-protein interaction, Gene Ontology enrichment, and KEGG pathway studies to clarify the underlying molecular mechanisms. The integrated study demonstrated considerable involvement of pathways linked with oxidative stress, inflammation, apoptosis, angiogenesis, and tumor growth, such as the PI3K/Akt and ERBB signaling pathways. Ellagic Acid has a higher binding affinity to EGFR (-8.6 kcal/mol) and ERBB2 (-7.5 kcal/mol) than the conventional medication Erlotinib, demonstrating persistent ligand-protein interactions. Zingerone also demonstrated good binding interactions with both target proteins. The results show that the synergistic combination of Zingerone and Ellagic Acid could be a promising multitarget treatment strategy against oral carcinogenesis.