Inhibition of nuclear translocation of notch intracellular domain (NICD) by diosgenin prevented atherosclerotic disease progression

Biochimie. 2018 May:148:63-71. doi: 10.1016/j.biochi.2018.02.011. Epub 2018 Feb 24.

Abstract

Notch signaling plays a pivotal role in homeostasis and cardiovascular development. The role of notch signaling in atherosclerosis cannot be complete without analysing the key role of notch in macrophages, which trigger the inflammatory response and subsequent plaque formation in atherosclerosis. Diosgenin showed its anti-atherosclerotic property by the unifying mechanism of suppressing the expression of notch signaling pathway, particularly the nuclear translocation of notch intracellular domain (NICD) in aorta and in differentiated macrophage cells. It is further confirmed by the inhibition of NICD by DAPT (N-[N-(3, 5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester), which also restricted the differentiation of macrophage. Hence, inhibition of nuclear translocation of NICD by diosgenin aids in preventing atherosclerosis.

Keywords: Atherogenic diet; DAPT; Diosgenin; Macrophage differentiation; Notch-NICD.

MeSH terms

  • Active Transport, Cell Nucleus / drug effects
  • Animals
  • Aorta / drug effects
  • Aorta / pathology
  • Atherosclerosis / pathology*
  • Cell Differentiation / drug effects
  • Cell Line
  • Cell Nucleus / drug effects*
  • Cell Nucleus / metabolism*
  • Diosgenin / pharmacology*
  • Disease Progression*
  • Macrophages / drug effects
  • Macrophages / pathology
  • Male
  • Protein Domains
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Receptors, Notch / chemistry*
  • Receptors, Notch / metabolism*
  • Signal Transduction / drug effects

Substances

  • RNA, Messenger
  • Receptors, Notch
  • Diosgenin