Ginsenosides Rg5 and Rh3 protect scopolamine-induced memory deficits in mice.

Panax ginseng (family Araliaceae) is traditionally used as a remedy for cancer, inflammation, stress and aging. To explore whether ginsenosides Rg5 and Rh3, the main constituents of heat-processed ginseng (the root of Panax ginseng), could protect memory deficit. We isolated ginsenosides Rh3 and Rg5 from heated-processed ginseng treated with and without human feces, respectively. Then we investigated their protective effects on memory impairment using the passive avoidance, Y-maze and Morris water maze tasks in mice. Memory deficit was induced in mice by the intraperitoneal injection of scopolamine. Ginsenosides Rg5 or Rh3 increased the latency time reduced by scopolamine in passive avoidance test. Treatment with ginsenoside Rg5 or Rh3 significantly reversed the lowered spontaneous alteration induced by scopolamine in Y-maze task. Ginsenoisde Rg5 or Rh3 (10 mg/kg) significantly shortened the escape latencies prolonged by treatment with scopolamine on the last day of training trial sessions in Morris water maze task. Furthermore, ginsenosides Rg5 and Rh3 inhibited acetylcholinesterase activity in a dose-dependent manner, with IC50 values of 18.4 and 10.2 μM, respectively. The inhibitory potency of ginsenoside Rh3 is comparable with that of donepezil (IC50=9.9 μM). These ginsenosides also reversed hippocampal brain-derived neurotrophic factor (BDNF) expression and cAMP response element-binding protein (CREB) phosphorylation reduced by scopolamine. Of them, ginsenoside Rh3 more potently protected memory deficit. Ginsenoside Rg5 and its metabolite ginsenoside Rh3 may protect memory deficit by inhibiting AChE activity and increasing BDNF expression and CREB activation.