Mechanism of action of <i>Aloe vera</i> against human papillomavirus‑positive head and neck squamous cell carcinoma

The present study aimed to evaluate the therapeutic targets of <i>Aloe vera</i> against human papillomavirus-positive (HPV⁺) head and neck squamous cell carcinoma (HNSCC), focusing on key bioactive components and their impact on molecular pathways, gene expression, overall survival and the tumor immune microenvironment. Using network pharmacology analysis, eight bioactive components of <i>Aloe vera</i> were identified, along with 244 corresponding potential therapeutic targets. Differential gene expression analysis of the GSE53355 and GSE117973 datasets revealed HPV⁺ HNSCC-specific genes. Using topological analysis of protein-protein interaction networks, serpin family member 1 (SERPINE1) was determined to be the core gene. Gene expression data were validated and survival analysis was performed, alongside molecular docking and experimental validation in HPV⁺ HNSCC cells. SERPINE1 was identified as a key gene that was markedly upregulated in HPV⁺ HNSCC, with a strong association with worse overall survival (P<0.0001). Genetic alterations in SERPINE1, primarily arm-level gains, were associated with immune cell infiltration, suggesting a role in tumorigenesis. Gene Set Enrichment Analysis showed the involvement of SERPINE1 in crucial cancer-associated pathways. Quercetin and SERPINE1 have strong binding affinity, as demonstrated by molecular docking, with experimental validation showing dose-dependent downregulation of SERPINE1 in HPV⁺ HNSCC cells. In conclusion, the bioactive component of <i>Aloe vera</i>, quercetin, exhibits potential in specifically targeting SERPINE1. The present discovery offers a potential therapeutic strategy for HPV⁺ HNSCC, particularly for enhancing patient survival outcomes. However, further in-depth investigations are essential to validate its therapeutic efficacy and underlying mechanisms within the intricate tumor microenvironment <i>in vivo</i>.