Wang Yunfei, Li Zhengrong, Liu Boxue, Wu Rumeng, Gong Haifeng, Su Zhanhai, Zhang Shoude
State Key Laboratory of Plateau Ecology and Agriculture, Qinghai University, Xining, Qinghai 810016, People's Republic of China.
Medical College of Qinghai University, Xining, Qinghai 810016, People's Republic of China.
Drug Des Devel Ther. 2020 Jan 15;14:167-173. doi: 10.2147/DDDT.S233013. eCollection 2020.
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.
在中国，异龙脑已用于治疗心血管疾病数年。然而，其机制仍不清楚。本研究的目的是确定异龙脑在动脉粥样硬化疾病应用中的新机制。
通过mRNA微阵列分析检测用/不用异龙脑处理的MCF-7细胞的全基因组基因表达谱。将基因表达谱之间的相似程度与连接图谱（CMAP）数据库进行比较。采用MTT法评估异龙脑对RAW 264.7细胞的毒性。还使用油红O染色和RAW 264.7细胞中的Dil-ox-LDL摄取试验来检测巨噬细胞中脂质的积累以及氧化低密度脂蛋白（ox-LDL）的摄取。
已证明异龙脑具有与抑制ox-LDL摄取的ikarugamycin相似的mRNA表达谱。这一过程已被证明是泡沫细胞形成和早期动脉粥样硬化病变的重要原因。因此，推测异龙脑可能表现出与ikarugamycin相似的活性。随后，结果表明，用不同浓度的异龙脑处理后，RAW 264.7细胞减少了ox-LDL的吸收和细胞内脂质的积累。
结果表明，异龙脑抑制巨噬细胞对ox-LDL的摄取，从而防止脂质在巨噬细胞中的积累。这些结果为异龙脑在动脉粥样硬化疾病中的应用提供了证据。
