Introduction
Aging is one of the most basic natural laws in the biological world. The
damage, degeneration, apoptosis, and neuron loss caused by oxidative
stress are significant contributors to neurodegenerative diseases and
brain aging. As the human body ages, stem cells inevitably drop in
number and function ( DE HG et al,2018). The senescence of stem cells is
closely related to the occurrence and progression of a wide variety of
diseases ( REN R et al,2017). The ability of neural stem cells (NSCs) to
regenerate declines with age, resulting in brain aging and dysfunction.
It has been linked to the development of neurodegenerative diseases such
as Alzheimer’s disease (AD), Parkinson’s disease (PD) (Zhu J et al,2014;
Glorioso C et al,2011). The brain is closely related to the occurrence
and development of NSCs, cognitive impairment, and neurodegenerative
diseases (Zhang Q et al,2016). Therefore, Therefore, it is critical to
investigate techniques to prevent the aging of the hippocampus and NSCs.
D-galactose (D-gal) is a well-established aging agent, and the aging
model it induces is strikingly comparable to natural aging ( Peng L
2011; Bei Y,2018; Chen LB,2018; Li G,2018; Zhao JC,2018). At present,
conventional wisdom is that cell aging is typically induced by oxidative
damage ( WU Q et al,2020). The theory suggests that when the number of
reactive oxygen species (ROS) produced in cells surpass the antioxidant
defense mechanism and accumulates, oxidative stress occurs, promoting
organisms and cells aging ( Jiang LD et al,2017; Yan HL et al,2011).
Ginseng is an important drug in Chinese medicine for invigorating Qi.
Ginsenoside Rg1 is the active ingredient of ginseng. Ginsenoside Rg1 has
been shown to have considerable anti-aging properties( Han SH et
al,2018; Leung KW et al,2007; Cheng Y et al,2005; Attele AS et al,2000).
This study established that ginsenoside Rg1 can antagonize
D-galactose-induced brain aging in mice, improve their behavior and
enhance the neurogenesis of the entire NSCs (Xiang Y et al,2017).
However, the molecular mechanism by which Rg1 delays hippocampal and NSC
senescence is unknown.
The Keap1-Nrf2/ARE signal transduction pathway is a critical antioxidant
pathway(Tu WJ et al,2019;Kundu JK et al,2010) . When stimulated by
appropriate oxidants,nuclear factor E2-related factor 2 (Nrf2) and
Kelch-like ECH-related protein 1 (Keap1) decompose and combine with
antioxidants in the response element (ARE) of the nucleus to initiate
transcription of cytoprotective genes, thereby protecting cells from
Oxidative damage and aging (Hybertson BM et al,2011). Nrf2 has been
found to be critical in preventing oxidative damage in studies (Ishii T
et al,2000). Therefore, we hypothesized that ginsenoside Rg1 delays the
aging of the hippocampus and NSCs via anti-oxidative stress damage and
is associated with the activation of the Keap1-Nrf2/ARE signaling
pathway.
This experiment combines traditional Chinese medicine, stem cell
research, and the aging regulation theory. Using D-gal as a model of
aging, we investigated whether ginsenoside Rg1 may delay the aging of
the hippocampus and NSCs by reducing oxidative stress damage, and is
mediated by the Keap1-Nrf2/ARE signaling pathway. By elucidating the
mechanism by which ginsenoside Rg1 delays the aging of the hippocampus
and NSCs, this study aims to provide a new direction for the prevention
and treatment of neurodegenerative diseases.