Systems biology and molecular modeling assisted exploration of the underlying mechanism of Safflower (Carthamus tinctorius L.) 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 Carthamus tinctorius, 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 C. tinctorius 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 C. tinctorius’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 C. tinctorius may have therapeutic potential for hearing loss by targeting key genes and pathways. However, further in-vivo and in-vitro studies are needed to confirm these findings and determine optimal treatment parameters.