Mechanisms of Semen Cassiae to Treat Hypercholesterolemia Based on Molecular Docking

Hypercholesterolemia is a major risk factor of cardiovascular disease with high prevalence rate. Studies have shown that the traditional Chinese medicine: Semen Cassiae can reduce blood cholesterol and lipids, but the functional components and molecular mechanisms need further elucidation. In this study, molecular docking technology is used to explore the mechanism of Semen Cassiae in the treatment of hypercholesterolemia. A total 88 active ingredients and 196 isomers of Semen Cassiae were obtained from the traditional Chinese medicine database: HERB. 6 hypercholesterolemia-related drug targets: proprotein convertase subtilisin/kexin type 9 (PCSK9), thyroid Hormone Receptor β (THRB), peroxisome proliferator-activated receptors (PPARd), 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR), insulin receptor (IR) and squalene monooxygenase (SQLE) were obtained from the Therapeutic Target Database. After data preprocessing, molecular docking analysis was conducted using the LibDock tool in Discovery Studio software, and the main “active ingredient-target” combinations with high scores were screened. The structure results showed high binding affinity of the active ingredients to the hypercholesterolemia-related targets. Gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed the involved pathways, including cholesterol and lipid metabolism, lipoprotein particle formation, cholesterol and lipid transfer and lipoprotein particle receptor binding processes. This study revealed that the anti-hypercholesterolemia activity of Semen Cassiae is a multicomponent, multitarget, and multipathway effects, and provides evidence for further development the clinical application value of Semen Cassiae on hypercholesterolemia.