Effects of ginseol k-g3, an Rg3-enriched fraction, on scopolamine-induced memory impairment and learning deficit in mice

Abstract

Background: Although ginsenosides such as Rg1, Rb1 and Rg3 have shown promise as potential nutraceuticals for cognitive impairment, their use has been limited due to high production cost and low potency. In particular, the process of extracting pure Rg3 from ginseng is laborious and expensive.

Methods: We described the methods in preparing ginseol k-g3, an Rg3-enriched fraction, and evaluated its effects on scopolamine-induced memory impairment in mice.

Results: Ginseol k-g3 (25-200 mg/kg) significantly reversed scopolamine-induced cognitive impairment in the passive avoidance, but not in Y-maze testing. Ginseol k-g3 (50 and 200 mg/kg) improved escape latency in training trials and increased swimming times within the target zone of the Morris water maze. The effect of ginseol k-g3 on the water maze task was more potent than that of Rg3 or Red ginseng. Acute or subchronic (6 d) treatment of ginseol k-g3 did not alter normal locomotor activity of mice in an open field. Ginseol k-g3 did not inhibit acetylcholinesterase activity, unlike donezepil, an acetylcholinesterase inhibitor. Rg3 enrichment through the ginseol k-g3 fraction enhanced the efficacy of Rg3 in scopolamine-induced memory impairment in mice as demonstrated in the Morris water maze task.

Conclusion: The effects of ginseol k-g3 in ameliorating scopolamine-induced memory impairment in the passive avoidance and Morris water maze tests indicate its specific influence on reference or long-term memory. The mechanism underlying the reversal of scopolamine-induced amnesia by ginseol k-g3 is not yet known, but is not related to anticholinesterase-like activity.

Keywords: Panax ginseng; Rg3; ginseol k-g3; memory; scopolamine.

Fig. 1

A representative HPLC chromatogram of ginseol k-g3 at 203 nm. (A) Ginsenosides Rg1, Rb1, Rc, Rg2, but not Rg3, were detected in the crude ginseng extracts. (B) Ginseol k-g3 (an Rg3-enriched fraction) contained 50.71 mg/g and 37.22 mg/g of the Rg3 s and r forms, respectively. It also contained other ginsenosides such as Rk1 and Rg5.

Fig. 2

Effects of ginseol k-g3 on locomotor activity of mice. The effects of single (A, B) and repeated treatment (C, D) of ginseol k-g3 at various dosages (12.5, 25, 50,100, and 200 mg/kg) on locomotor activity of mice were examined. The following parameters were measured: moved distance and rearing frequency. The effects of Red ginseng (100 mg/kg), Rg3 (20 and 40 mg/kg) and donepezil (DNZ, 5 mg/kg) were also evaluated for comparison. Data represent mean ± SEM (n = 8-10 animals).

Fig. 3

Effects of ginseol k-g3 on the Y-maze task. The effects of single treatment of ginseol k-g3 at various dosages (12.5, 25, 50, 100, and 200 mg/kg), Red ginseng (100 mg/kg), Rg3 (20 and 40 mg/kg) and donepezil (DNZ, 5 mg/kg), or the same volume saline (Control) on spontaneous alternation behavior (A) and total arm entries (B) of mice treated with scopolamine were examined. Data represent mean ± SEM (n = 8-10 animals). *p < 0.01, significant vs. control group, **p < 0.01 significant vs. scopolamine-treated group.

Fig. 4

Effects of ginseol k-g3 on the passive avoidance task. The effects of single treatment of ginseol k-g3 at various dosages (12.5, 25, 50, 100, and 200 mg/kg), Red ginseng (100 mg/kg), Rg3 (20 and 40 mg/kg) and donepezil (DNZ, 5 mg/kg), or the same volume of saline (Control) on passive avoidance behavior of scopolamine-treated rats were examined. Data represent mean ± SEM (n = 8-10 animals). #p < 0.05, significant vs. Control group, *p < 0.05; **p < 0.01 significant vs. scopolamine-treated group.

Fig. 5

Effects of ginseol k-g3 on the Morris water maze task. The effects of ginseol k-g3 at various dosages (25, 50, 100, and 200 mg/kg), Red ginseng (100 mg/kg), Rg3 (20 and 40 mg/kg) and donepezil (DNZ, 5 mg/kg), or the same volume saline solution (Control) on escape latency (A) during water maze training session of mice treated with scopolamine were examined. (B) Effects of test drugs on swimming time and (C) speed during the probe trial session of the water maze test. Probe trials were performed over 2 min as described in Methods. Data represent mean ± SEM (n = 8-10 animals). #p < 0.05; ##p < 0.01 .significant vs. Control group, *p < 0.05; **p < 0.01, significant vs. scopolamine-treated group.

Fig. 6

Effects of ginseol k-g3 on acetylcholinesterase (AChE) activity in vitro. The effects of ginseol k-g3, Red ginseng, Rg3 and donepezil on acetylcholinesterase (AChE) activity inhibition were examined. The % change of AChE activities were determined as described in Methods. Error bars show mean ± SEM from 3 independent experiments.