Identification of Cellular Isoschaftoside-Mediated Anti-Senescence Mechanism in RAC2 and LINC00294

Molecules. 2024 Sep 4;29(17):4182. doi: 10.3390/molecules29174182.

Abstract

As cellular senescence, reactive oxygen species (ROS) accumulate excessively, causing cellular damage. Flavonoids derived from natural products are known for their antioxidant effects and their ability to delay cellular senescence. Previous studies have attempted to mitigate cellular senescence using flavonoids from natural sources. However, the detailed mechanisms and regulatory targets of some flavonoids exhibiting antioxidant effects have not been fully elucidated. Therefore, we screened a library of flavonoids for antioxidant properties. Isoschaftoside, a glycosidic flavonoid, significantly reduced ROS levels in senescent cells. It was found that mitochondrial function was restored, and dependence on glycolysis was reduced in senescent cells treated with isoschaftoside. Additionally, we identified that isoschaftoside suppresses ROS by reducing the expression of RAC2 and LINC00294 in senescent cells. Taken together, this study establishes a novel mechanism for ROS inhibition and the regulation of cellular senescence by isoschaftoside. Our findings contribute important insights to antioxidant and anti-senescence research.

Keywords: flavonoid; isoschaftoside; reactive oxygen species (ROS); senescence amelioration.

MeSH terms

  • Antioxidants* / chemistry
  • Antioxidants* / pharmacology
  • Cell Line
  • Cellular Senescence* / drug effects
  • Flavonoids / chemistry
  • Flavonoids / pharmacology
  • Glycosides / chemistry
  • Glycosides / pharmacology
  • Humans
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • RAC2 GTP-Binding Protein*
  • Reactive Oxygen Species* / metabolism
  • rac GTP-Binding Proteins* / genetics
  • rac GTP-Binding Proteins* / metabolism

Substances

  • Reactive Oxygen Species
  • rac GTP-Binding Proteins
  • RAC2 GTP-Binding Protein
  • Antioxidants
  • Glycosides
  • Flavonoids