Nitro Dihydrocapsaicin, a Non-Pungent Capsaicin Analogue, Inhibits Cellular Senescence of Lens Epithelial Cells via Upregulation of SIRT1

Int J Mol Sci. 2022 Nov 12;23(22):13960. doi: 10.3390/ijms232213960.

Abstract

Diabetic cataracts are a common complication that can cause blindness among patients with diabetes mellitus. A novel nitro dihydrocapsaicin (NDHC), a capsaicin analog, was constructed to have a non-pungency effect. The objective of this research was to study the effect of NDHC on human lens epithelial (HLE) cells that lost function from hyperglycemia. HLE cells were pretreated with NDHC before an exposure to high glucose (HG) conditions. The results show that NDHC promoted a deacceleration of cellular senescence in HLE cells. This inhibition of cellular senescence was characterized by a delayed cell growth and lower production of reactive oxygen species (ROS) as well as decreased SA-β-galactosidase activity. Additionally, the expression of Sirt1 protein sharply increased, while the expression of p21 and phospho-p38 proteins decreased. These findings provide evidence that NDHC could exert a pharmacologically protective effect by inhibiting the senescence program of lens cells during diabetic cataracts.

Keywords: SIRT1; diabetic cataract; lens epithelial cell; oxidative stress; senescence.

MeSH terms

  • Capsaicin / pharmacology
  • Cataract*
  • Cellular Senescence
  • Epithelial Cells
  • Humans
  • Sirtuin 1* / genetics
  • Up-Regulation

Substances

  • Sirtuin 1
  • dihydrocapsaicin
  • Capsaicin
  • SIRT1 protein, human