Improvement of Memory in Mice and Increase of Hippocampal Excitability in Rats by Ginsenoside Rg1’s Metabolites Ginsenoside Rh1 and Protopanaxatriol

Abstract

Abstract. Ginsenoside Rg1 has been reported to improve cognitive function in many memoryimpaired animal models. However, little is known about the bioactivity of its metabolites in the central nervous system in vivo. In the present study, we employed the step through test and electrophysiological approach to investigate the effects of ginsenoside Rg1's primary metabolite ginsenoside Rh1 and end metabolite protopanaxatriol (Ppt) on learning and memory as well as hippocampal excitability. The behavioral study showed that both ginsenoside Rh1 and Ppt significantly ameliorated memory-impaired models induced by scopolamine in mice. Consistently, the electrophysiological work revealed that ginsenoside Rh1 and Ppt as well as their precursor ginsenoside Rg1 all increased hippocampal excitability in the dentate gyrus of anesthetized rats. These results demonstrated that both ginsenoside Rh1 and Ppt had similar but more potent actions than ginsenoside Rg1 in improving memory and hippocampal excitability, suggesting the role of ginsenoside's sugar moieties in biological activities is not as necessary as traditionally considered.

Ginsenoside Rh1: A Systematic Review of Its Pharmacological Properties

“…In the Morris water maze test, G-Rh1 (10 mg/kg) markedly decreased the escape latency, and increased the number of crosses and the time spent in the platform, thereby improving the spatial learning ability [59]. Moreover, Wang et al [58] found that the pain threshold was not affected in the tail-flick test, confirming the nootropic effect of G-Rh1. Lee et al [60] compared the effects of seven ginsenosides on neural activity by measuring changes in the slope of fEPSPs.…”

“…There was no general conclusion for quality of the whole study. There are six studies that claimed the animals were divided randomly [22,44,50,58,59,70]. However, no study presented any method to generate the allocation sequence.…”

“…Regarding the baseline characteristic item, seven studies showed the balance of relevant baseline characteristics between the control group and the intervention group [38,45,47,48,50,58,59]. No study noted any adjustment if the unequal distribution of some relevant baseline characteristics in analysis had existed.…”

“…Nevertheless, only one study showed that its outcome would be biased due to not complying with this process [58]. We determined this outcome was due to their measurement being dependent on a subjective awareness of the assessors.…”

“…By the passive avoidance test, pretreatment of G-Rh1 at doses of 5 and 10 mg/kg was observed to significantly improve the learning ▶ [57] and memory in mice with scopolamine-induced memory impairment [58] or saline-treated mice [59]. In the Morris water maze test, G-Rh1 (10 mg/kg) markedly decreased the escape latency, and increased the number of crosses and the time spent in the platform, thereby improving the spatial learning ability [59].…”