Ginsenoside Rg1 Promotes the Survival, Proliferation, and Differentiation of Senescent Neural Stem Cells Induced by D-galactose

Actas Esp Psiquiatr. 2025 Jan;53(1):49-61. doi: 10.62641/aep.v53i1.1812.

Abstract

Background: Neural stem cells (NSCs) disrupt with aging, contributing to neurodegeneration. Ginsenoside Rg1 (Rg1), a compound found in Ginseng, is known for its anti-aging effects; however, its role in the progression of aging NSCs remains unclear. Therefore, this investigation explored the impact of Rg1 on the growth and maturation of aging NSC and elucidated its underlying molecular mechanisms.

Methods: Initially, mouse models of brain aging were successfully established using D-galactose (D-gal) injection. Mice received Rg1 treatment along with D-gal administration. Brain tissues and NSCs were isolated and analyzed for pathological changes, gene expression, and cellular function. In vitro, experiments used aging NSCs treated with Rg1 to assess cell viability, proliferation, differentiation, and senescence markers.

Results: D-gal triggered aging-related pathological alterations in mouse brains, elevated acetylcholinesterase levels, upregulated senescence genes, and inhibited NSC proliferation (p < 0.05). However, Rg1 treatment mitigated D-gal-induced effects, delayed brain aging, and improved NSC function. In vitro, Rg1 significantly increased cell viability, promoted NSC proliferation and differentiation, reduced senescent neurons, and downregulated p53 and p21 genes (p < 0.05).

Conclusions: Rg1 demonstrates anti-aging properties in D-gal-induced mouse brain aging, promoting the proliferation and differentiation of NSCs, and downregulating the p53-p21 signaling pathway.

MeSH terms

  • Animals
  • Cell Differentiation* / drug effects
  • Cell Proliferation* / drug effects
  • Cell Survival* / drug effects
  • Cellular Senescence* / drug effects
  • Galactose* / pharmacology
  • Ginsenosides* / pharmacology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neural Stem Cells* / drug effects
  • Neural Stem Cells* / metabolism

Substances

  • Ginsenosides
  • ginsenoside Rg1
  • Galactose

Grants and funding

This study was supported by the National Natural Science Foundation of China (nos. 81873103 and 81673748) and Natural Science Foundation of Chongqing (nos. cstc2019jcyj-msxmX0850 and cstc2021jcyj-msxmX0669).