Lab Anim Res.  2015 Jun;31(2):69-77. 10.5625/lar.2015.31.2.69.

Prolonged oral administration of Gastrodia elata extract improves spatial learning and memory of scopolamine-treated rats

• Park YM
• Lee BG
• Park SH
• Oh HG
• Kang YG
• Kim OJ
• Kwon LS
• Kim YP
• Choi MH
• Jeong YS
• Oh J
• Lee HY

• KMID: 2053680
• DOI: http://doi.org/10.5625/lar.2015.31.2.69

Abstract

Gastrodia elata (GE) is traditionally used for treatment of various disorders including neurodegenerative diseases such as Alzheimer's disease. To investigate the neuroprotective effect of GE, amyloid-beta peptide (Abeta)-treated PC12 cells were cultured with GE aqueous extract. In vitro assay demonstrated that 50 microM of pre-aggregated Abeta was lethal to about a half portion of PC12 cells and that Abeta aggregate-induced cell death was significantly decreased with GE treatment at < or =10 mg/mL in a dose-dependent manner. To further examine in vivo cognitive-improving effects, an artificial amnesic animal model, scopolamine-injected Sprague-Dawley rats, were orally administered the extract for 6 weeks followed by behavioral tests (the passive avoidance test and Morris water maze test). The results showed that an acute treatment with scopolamine (1 mg/kg of body weight) effectively induced memory impairment in normal rats and that the learning and memory capability of scopolamine-treated rats improved after prolonged administration of GE extract (50, 250 and 500 mg/kg of body weight for 6 weeks). These findings suggest that a GE regimen may potentially ameliorate learning and memory deficits and/or cognitive impairments caused by neuronal cell death.

Keyword

Gastrodia elata; scopolamine-induced memory impairment; amyloid-beta peptide; neuroprotective effect; cognitive-enhancing effect

MeSH Terms

Administration, Oral*
Alzheimer Disease
Animals
Body Weight
Cell Death
Gastrodia*
Learning*
Memory Disorders
Memory*
Models, Animal
Neurodegenerative Diseases
Neurons
Neuroprotective Agents
PC12 Cells
Rats*
Rats, Sprague-Dawley
Scopolamine Hydrobromide
Neuroprotective Agents
Scopolamine Hydrobromide

Figure

• 

  Figure 1 Protective effect of GE against Aβ-induced neural cell death. (A) Cytotoxicity of GE sample at 0, 0.01, 0.05, 0.5, 1, 5, 10, 20 and 30 mg/mL applied to PC12 cells was examined. Relative cell viability normalized to the control (100, 96, 93, 94, 95, 93, 91, 65, and 47% at each concentration) decreased in a dose-dependent manner. N=5; error bars, mean±SEM. (B) Cytotoxicity of PC12 cells treated with pre-aggregated Aβ at 0, 5, 10, 20, 40, 50, 70 and 100 µM was assayed. Relative cell viability (normalized to the control; 100% at the 0-µM-treated condition) was decreased in a dose-dependent manner, 88.3, 78.9, 77.8, 62.9, 56.8, 42.8, and 23.4% on average at each respective concentration. N=5; error bars, mean±SEM. (C) The neural cell protective effect of GE against Aβ-induced cytotoxicity was evaluated. PC12 cells were pretreated with GE at various concentrations (0-10 mg/mL) for 1 hr and cultured in the presence of 50 µM of Aβ for 48 hr. Cell viability under GE-treated conditions were significantly higher compared to controls (no GE-treated). N=7; error bars, mean±SEM.

• 

  Figure 2 Weekly changes in the body weight, food intake and water intake. Sprague-Dawley rats were randomly assigned to five different groups (10 rats per group): No treatment, only scopolamine-treated, and GE extract and scopolamine-treated groups [GElow (50 mg of sample/kg of body weight), GEmid (250 mg/kg) and GEhigh (500 mg/kg)]. Body weight (A), food intake (B) and water intake (C) were monitored on a weekly basis for 7 weeks and within-group measurements for each week were averaged. There were no significant differences observed over the study period.

• 

  Figure 3 Ameliorative efficacy of oral administration of GE extract on memory impairment. Sprague-Dawley rats were randomly assigned to five different groups (10 rats per group): No treatment, only scopolamine-treated, and GE extract-administered at three different concentrations (50, 250 and 500 mg/kg body weight) with scopolamine-treated. Before learning and memory tests (A, passive avoidance test; B, Morris water maze test), rats were treated according to the experimental group and trained multiple times for a week to escape from the given circumstances. After training, acute memory impairment was induced by an intraperitoneal injection of scopolamine (1 mg/kg of body weight) on the day of the test. (A) Results from the passive avoidance test showed that the escape latency time was maximized to 180 sec for the scopolamine-injected group (control) compared to that for the normal group (69 sec). The latency time was significantly lowered in the groups that received GE extract treatment compared to controls. (B) Data from the Morris water maze test showed that prolonged administration of GE extract to the scopolamine-treated rat hypomnesic model decreased the escape latency time compared to the control group (no GE extract treatment).

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