Isoborneol Attenuates Low-Density Lipoprotein Accumulation and Foam Cell Formation in Macrophages

• Published in: Drug design, development and therapy Vol. 14; pp. 167 - 173
• Main Authors: Wang, Yunfei, Li, Zhengrong, Liu, Boxue, Wu, Rumeng, Gong, Haifeng, Su, Zhanhai, Zhang, Shoude
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 2020; Taylor & Francis Ltd; Dove; Dove Medical Press
• Subjects: Accumulation; Algorithms; Animals; Antibiotics; Arteriosclerosis; Atherosclerosis; Biochemistry; Camphanes - pharmacology; Cardiovascular disease; Cardiovascular diseases; Cell Survival - drug effects; Cells, Cultured; Comparative analysis; connectivity map; Density; Diseases; DNA microarrays; Dose-Response Relationship, Drug; Drugs; Foam Cells - cytology; Foam Cells - drug effects; Foam Cells - metabolism; Gene expression; Genes; Genomes; Genomics; ikarugamycin; isoborneol; Lipids; Lipoproteins; Lipoproteins, LDL - antagonists & inhibitors; Lipoproteins, LDL - metabolism; Low density lipoprotein; Low density lipoproteins; macrophage; Macrophages; Medical treatment; Messenger RNA; Mice; Novels; Original Research; ox-ldl; Penicillin; RAW 264.7 Cells; RNA; Scientific equipment industry; Structure-Activity Relationship; Toxicity; United States; China; Beijing China; United States > US; Japan; Finland; atherosclerosis; macrophage; isoborneol; connectivity map; ikarugamycin; ox-LDL
• ISSN: 1177-8881; 1177-8881
• DOI: 10.2147/DDDT.S233013

Isoborneol has been used in the treatment of cardiovascular disease for several years in China. However, the mechanism is still unclear. The aim of this study was to identify the novel mechanism of isoborneol for its application in atherosclerotic disease. The whole-genome gene expression profiles of MCF-7 cells treated with/or without isoborneol were detected by mRNA microarray analysis. The degree of similarity between the gene expression profiles was compared with the Connectivity Map (CMAP) database. An MTT assay was used to assess the toxicity of isoborneol on RAW 264.7 cells. Oil red O staining and a Dil-ox-LDL uptake assay in RAW 264.7 cells were also used to detect the accumulation of lipids in the macrophages and the uptake of oxidized low-density lipoprotein (ox-LDL). Isoborneol was proved to have mRNA expression profiles similar to that of ikarugamycin which can inhibit the uptake of ox-LDL. This process has proved to be an important cause of foam cell formation and early atherosclerotic lesions. It is speculated, therefore, that isoborneol may show similar activity to that shown by ikarugamycin. Subsequently, it was shown that RAW 264.7 cells reduced the absorption of ox-LDL and the accumulation of intracellular lipids after treatment with different concentrations of isoborneol. The results indicate that isoborneol inhibits macrophage consumption of ox-LDL, thereby preventing the accumulation of lipids in the macrophages. These results provide evidence for the application of isoborneol in atherosclerotic disease.