Long-term administration of ginsenoside Rh1 enhances learning and memory by promoting cell survival in the mouse hippocampus

Ginsenosides, the secondary plant metabolites produced by Panax ginseng are responsible for the enhancing effects on learning observed following treatment with Panax ginseng. A number of studies have provided correlational evidence that cell proliferation and survival are closely associated with hippocampal-dependent learning tasks. In this study, to investigate the beneficial effects of ginsenoside Rh-1 on hippocampal cells and learning, mice (6 months old) were administered ginsenoside Rh-1 at a dose of 5 and 10 mg/kg/day for a period of 3 months. Saline-treated mice were used as controls. The enhancement of memory and learning in the mice was evaluated by hippocampal-dependent tasks (passive avoidance tests and Morris water maze tests) and the immunohistochemical marker of cell proliferation, bromodeoxyuridine (BrdU). In addition, the levels of brain-derived neurotrophic factor (BDNF) were measured following treatment. Based on our data, the Rh-1-treated group (5 and 10 mg/kg) showed a significantly improved learning and memory ability in the passive avoidance tests compared with the control group; however, only treatment with 10 mg/kg ginsenoside Rh-1 significantly promoted spatial learning ability in the Morris water maze test. Ginsenoside Rh-1 significantly enhanced cell survival in the dentate gyrus of mice, although it did not enhance hippocampal cell proliferation. In addition, ginsenoside Rh-1 upregulated the expression of BDNF. These findings address the potential therapeutic significance of ginsenoside Rh-1 as a nutritional supplement in memory loss and neurodegenerative diseases.