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.