HDL biology
Bioinformatics and molecular docking identify the soy isoflavone genistein as binding CETP among three key HDL-raising natural-product targets (J Transl Med 2023)
Original title: Identifying the natural products in the treatment of atherosclerosis by increasing HDL-C level based on bioinformatics analysis, molecular docking, and in vitro experiment
Because HDL cholesterol protects against atherosclerosis through reverse cholesterol transport, researchers screened for natural products that could raise HDL cholesterol to treat atherosclerosis. Combining differential gene analysis, a protein-protein interaction network, node-importance calculations, and KEGG pathway enrichment, they narrowed 758 atherosclerosis-related genes down to three key targets: APOA1, LIPC, and CETP. Molecular docking screening of natural compounds found that genistein, a soy isoflavone, showed good binding affinity for all three targets, APOA1, CETP, and LIPC. In an in vitro foam cell model, genistein treatment upregulated expression of APOA1, LIPC, and CETP, suggesting genistein may raise HDL cholesterol and exert anti-atherosclerotic effects through coordinated regulation of these three lipid-metabolism genes.
Original abstract
Background: Previous studies have demonstrated that high-density lipoprotein cholesterol (HDL-C) plays an anti-atherosclerosis role through reverse cholesterol transport. Several studies have validated the efficacy and safety of natural products in treating atherosclerosis (AS). However, the study of raising HDL-C levels through natural products to treat AS still needs to be explored.
Methods: The gene sets associated with AS were collected and identified by differential gene analysis and database query. By constructing a protein-protein interaction (PPI) network, the core submodules in the network are screened out. At the same time, by calculating node importance (Nim) in the PPI network of AS disease and combining it with Kyoto Encyclopedia of genes and genomes (KEGG) pathways enrichment analysis, the key target proteins of AS were obtained. Molecular docking is used to screen out small natural drug molecules with potential therapeutic effects. By constructing an in vitro foam cell model, the effects of small molecules on lipid metabolism and key target expression of foam cells were investigated.
Results: By differential gene analysis, 451 differential genes were obtained, and a total of 313 disease genes were obtained from 6 kind of databases, then 758 AS-related genes were obtained. The enrichment analysis of the KEGG pathway showed that the enhancement of HDL-C level against AS was related to Lipid and atherosclerosis, Cholesterol metabolism, Fluid shear stress and atherosclerosis, PPAR signaling pathway, and other pathways. Then we intersected 31 genes in the core module of the PPI network, the top 30 genes in Nims, and 32 genes in the cholesterol metabolism pathway, and finally found 3 genes. After the above analysis and literature collection, we focused on the following three related gene targets: APOA1, LIPC, and CETP. Molecular docking showed that Genistein has a good binding affinity for APOA1, CETP, and LIPC. In vitro, experiments showed that Genistein can up-regulated APOA1, LIPC, and CETP levels.
Conclusions: Based on our research, Genistein may have the effects of regulating HDL-C and anti-atherosclerosis. Its mechanism of action may be related to the regulation of LIPC, CETP, and APOA1 to improve lipid metabolism.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.