Study on the mechanism of action of probucol in the treatment of coronary artery disease based on network pharmacology and molecular docking technology

Abstract Objective The latest studies have shown that the combined use of aggressive lipid-lowering and inflammation-reducing therapies might reduce atherosclerotic risk. Probucol has hypolipidemic, antioxidative, and anti-inflammatory effects. Through network pharmacology and molecular docking, the core genes, biological function, and signalling pathways of Probucol in coronary artery disease/coronary heart disease were revealed. Methods Pharmacological targets of probucol were screened using the SuperPred, Similarity ensemble approach (SEA), and STITCH databases. Similarly, the pathological targets of CAD/CHD were obtained through the DisGeNET, National Center for Biotechnology Information (NCBI), and GeneCard databases. Then, all common targets of probucol against CAD/CHD were screened by an online platform. Seven core targets were obtained through six algorithms of the CytoHubba plugin of Cytoscape and the online platform Jvenn. Finally, the core genes were analysed by GO and KEGG enrichment analyses and molecular docking technology was utilized to verify the core gene prediction and further confirm the target and mechanism of probucol in CAD/CHD. Results By screening the targets of probucol and CAD/CHD, 121 pharmacological targets, 11403 pathological targets, and 84 common targets were obtained; furthermore, seven core targets were identified. These core targets were SCARB1, APOE, VCAM1, NF-кB, HIF1A, PTPN11 and SLC2A1. In addition, the enrichment analysis results indicated that probucol might treat CAD/CHD by regulating cholesterol imbalance and anti-inflammatory and antioxidant activities. The molecular docking results showed that probucol binds well to the core targets associated with CAD/CHD. Conclusion Probucol might be involved in regulating cholesterol imbalance and anti-inflammatory and antioxidant activities based on its regulation of SCARB1, APOE, VCAM1, NF-кB, HIF1A, PTPN11 and SLC2A1. Strategies targeting these biotargets may be used to treat CAD/CHD in future clinical practice.