Ginsenoside Rg1 Delays the Aging of Mouse Hippocampus and NSCs Through the Keap1-Nrf2/ARE Pathway

Aging can be caused by oxidative stress. Keap1-Nrf2/ARE signaling pathway is an antioxidant pathway. Ginsenoside Rg1 is one of the saponins found in ginseng having biological activity. It possesses anti-aging, anti-oxidant, and immune-strengthening properties. However, the molecular mechanism through which Rg1 affects brain aging is unknown. The purpose of this study was to investigate the effect of ginsenoside Rg1 in aging mice models and to decipher the molecular mechanisms underlying hippocampal aging and NSCs. D-gal was used to construct a mouse brain and NSCs aging model. Rg1 treatment improved brain function; decreased the structural damage of D-gal to hippocampal tissue and cells; decreased Ach neurotransmitter degradation; down-regulated the expression of the aging-related protein P53; alleviated oxidative stress damage: increased SOD and CAT activities, decreased MDA, 4-HNE and 8-OHdG content; down-regulated Keap1 protein expression and promoted Nrf2 dissociation from Keap1, and up-regulated Nrf2 and HO-1 protein expression, thus activating the Keap1-Nrf2/ARE pathway; Up-regulated expression of Nrf2/ARE pathway-related protective target genes (NQO1, GCLM, GSTM-1, and GCLC), reducing the aging process caused by D-gal-induced oxidative stress damage. Conclusion: Ginsenoside Rg1 can protect the hippocampus and NSCs of mice from oxidative damage and delay aging via the Keap1-Nrf2/ARE pathway.It advances our understanding of antioxidant therapy, serves as a critical reference for the prevention and treatment of aging-related disorders of the nervous system, and gives new scientific connotations to the Chinese medicine.