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Isoborneol Attenuates Low-Density Lipoprotein Accumulation and Foam Cell Formation in Macrophages
Yunfei Wang1,2, Zhengrong Li2, Boxue Liu1,2
1State Key Laboratory of Plateau Ecology and Agriculture, Qinghai University, Xining, Qinghai 810016, People's Republic of China.
Purpose:
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.
Materials And Methods:
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).
Results:
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.
Conclusion:
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.
Insights
Isoborneol inhibits oxidized low-density lipoprotein (ox-LDL) uptake by macrophages, reducing lipid accumulation and preventing early atherosclerotic lesions. This finding reveals a novel mechanism for isoborneol in treating cardiovascular disease.
Area of Science:
- Pharmacology
- Biochemistry
- Cardiovascular Research
Background:
- Isoborneol is utilized in China for cardiovascular disease treatment, but its precise mechanism remains elusive.
- Atherosclerosis, a cardiovascular disease, is characterized by lipid accumulation in macrophages, leading to lesion formation.
Purpose of the Study:
- To elucidate the novel mechanism of isoborneol in the context of atherosclerotic disease.
- To investigate isoborneol's effects on macrophage lipid uptake and accumulation.
Main Methods:
- Whole-genome gene expression profiling of MCF-7 cells treated with isoborneol using mRNA microarray analysis.
- Comparison of gene expression profiles with the Connectivity Map (CMAP) database.
- Assessment of isoborneol's toxicity on RAW 264.7 cells via MTT assay, and evaluation of lipid accumulation and oxidized low-density lipoprotein (ox-LDL) uptake using Oil red O staining and Dil-ox-LDL assay.
Main Results:
- Isoborneol exhibited mRNA expression profiles similar to ikarugamycin, a known inhibitor of ox-LDL uptake.
- RAW 264.7 macrophages treated with isoborneol demonstrated reduced ox-LDL absorption and intracellular lipid accumulation.
- These findings suggest isoborneol's potential to inhibit foam cell formation, a key event in early atherosclerosis.
Conclusions:
- Isoborneol effectively inhibits macrophage uptake of ox-LDL, thereby preventing lipid accumulation.
- This mechanism provides a scientific basis for the therapeutic application of isoborneol in managing atherosclerotic disease.
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