Searching for Hub Genes of Quince–Basil Co-Administration Against Atherosclerosis Using Bioinformatics Analysis and Experimental Validation

Background: Atherosclerosis (AS) has one of the highest rates of morbidity and death globally. Cydonia oblonga Mill. (quince, COM) and Ocimum basilicum L. (basil, OB) are Uyghur medicines that are often used for anti-inflammatory, anti-tumor, and cardiovascular disease treatment. This study aimed to uncover the hub genes of the quince-basil co-administration against AS and validate them. Methods: Network pharmacology analysis and bioinformatics analysis methods were utilized to map the network and obtain four hub genes. Experiments were performed in vivo and in vitro using HUVEC and zebrafish to validate the therapeutic effect of COM-OB co-administration against AS. Finally, the hub genes were validated by Western blot. Results: Screening by network pharmacology analysis and bioinformatics analysis obtained a total of 3302 drug targets, 1963 disease targets, and 1630 DEGs. A series of bioinformatic analyses were utilized to ultimately screen four hub genes, and the stability was also verified by molecular docking and molecular dynamics. COM-OB total flavonoids co-administration significantly decreased PA-induced lipid deposition in HUVEC and reduced high cholesterol-induced fat accumulation in zebrafish. Western blot results showed that COM-OB co-administration significantly affected the expression of hub genes. Conclusions: The study identified and validated four hub genes, COL1A1, COL3A1, BGLAP, and NOX4, thus providing a rationale for the treatment of AS with COM and OB co-administration.