Drug Design, Development and Therapy (Jan 2020)

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

  • Wang Y,
  • Li Z,
  • Liu B,
  • Wu R,
  • Gong H,
  • Su Z,
  • Zhang S

Journal volume & issue
Vol. Volume 14
pp. 167 – 173

Abstract

Read online

Yunfei Wang, 1, 2,* Zhengrong Li, 2,* Boxue Liu, 1, 2 Rumeng Wu, 1, 2 Haifeng Gong, 2 Zhanhai Su, 2 Shoude Zhang 1, 2 1State Key Laboratory of Plateau Ecology and Agriculture, Qinghai University, Xining, Qinghai 810016, People’s Republic of China; 2Medical College of Qinghai University, Xining, Qinghai 810016, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shoude ZhangState Key Laboratory of Plateau Ecology and Agriculture, Qinghai University, 251# Ningda Road, Xining, Qinghai 810016, People’s Republic of ChinaTel +86-971-5366433Fax +86-971-5201533Email [email protected]: 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.Keywords: isoborneol, ikarugamycin, connectivity map, ox-LDL, atherosclerosis, macrophage

Keywords