Systems biology and molecular modeling assisted exploration of the underlying mechanism of Safflower (<i>Carthamus tinctorius L.</i>) in the treatment of hearing loss

Hearing loss is the incapability to hear sound, either partially or fully. One potential natural remedy for hearing loss is the use of <i>Carthamus tinctorius</i>, commonly known as safflower, contains bioactive compounds, including flavonoids, phenolic acids, and terpenoids, which possess potent antioxidant and anti-inflammatory activities. This study uses network pharmacology to identify the potential therapeutic effects of these compounds on hearing loss. We identified 17 active compounds of <i>C. tinctorius</i> with favorable ADME properties through a litrature search. Potential targets for these compounds were found using databases like STITCH and Swiss Target Prediction, as well as the GeneCards database to retrieve hearing loss-related potential targets. A Venn diagram was drawn to determine shared targets, and GO enrichment and KEGG pathways analysis of 64 key targets were conducted DAVID database. Protein-protein interactions (PPIs) were analyzed via STRING database, and a compound-target-pathway network was created in Cytoscape. Molecular docking studies focused on one hub gene, namely, tumor necrosis factor (TNF) revealing that <i>C. tinctorius</i>’s compounds have high affinity for TNF, suggesting a potential therapeutic link to hearing loss. Finally, molecular dynamics simulations and calculations of binding free energy showed TNF_Beta Sitosterol and TNF_Campesterol were more stable than TNF_Cholesterol. Our findings indicate that <i>C. tinctorius</i> may have therapeutic potential for hearing loss by targeting key genes and pathways. However, further <i>in-vivo</i> and <i>in-vitro</i> studies are needed to confirm these findings and determine optimal treatment parameters.