Ellagic acid and α-mangostin in oral gel formulations show anticancer, antiviral, and anti-inflammatory activities in vitro

This study aimed to develop two oral gel formulations containing ellagic acid (EA) and α-mangostin (α-MG), and evaluate their anticancer, antiviral, and anti-inflammatory activities. Cytotoxicity and anticancer potential were assessed via MTT assay in oral squamous carcinoma (SCC-25), oral keratinocytes (OKC), murine macrophages (RAW264.7), and human gingival fibroblasts (HGF). Antiviral activity against herpes simplex virus type 1 (HSV-1) was evaluated using plaque reduction assays, while effects on human papillomavirus type 16 (HPV-16) were analyzed using a pseudovirus model targeting both attachment and post-attachment infection stages. Anti-inflammatory effects were determined by nitric oxide (NO) quantification in LPS-stimulated RAW264.7 cells. The formulations showed selective cytotoxicity toward SCC-25 cells, indicating anticancer potential. Both EA and α-MG significantly inhibited HSV-1 infection at the pre- and post-entry stage, and the two gel formulations were effective in post-infection treatments. However, no inhibitory activity was observed against HPV-16 pseudovirus, suggesting no interaction with L1/L2 capsid proteins. Additionally, both formulations markedly reduced NO production, demonstrating strong anti-inflammatory activity. In summary, EA and α-MG gels exhibited promising anticancer, anti-HSV-1, and anti-inflammatory properties, supporting their potential use in managing oral cancer and HSV-1-related oral conditions. They showed no efficacy against HPV-16 infection.