Antiamnesic Effects of Feralolide Isolated from Aloe vera Resin Miller against Learning Impairments Induced in Mice

Abstract

Feralolide, a dihydroisocoumarin, was isolated from the methanolic extract of resin of Aloe vera. The present study aims to investigate the in vivo ability of feralolide to ameliorate memory impairment induced by scopolamine using a battery of in vitro assays, such as antioxidant and acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibition, and in vivo animal models, including elevated plus maze, Morris water maze, passive avoidance, and novel object recognition tests. Feralolide caused a concentration-dependent inhibition of AChE and BuChE enzymes with IC50 values of 55 and 52 μg/mL, respectively, and antioxidant activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2, 2′-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) with IC50 values 170 and 220 μg/mL, respectively. Feralolide reversed the scopolamine-induced amnesia as indicated by a dose-dependent decrease in escape latency, path length, and passing frequency in the Morris water maze test compared with the relevant control. The compound also significantly increased the discrimination index in a dose-dependent manner in NORT and decreased transfer latency in EPM, reflective of its memory-enhancing effect. Furthermore, feralolide also caused significant dose-dependent elevation in the step-down latency (SDL) in the passive avoidance test. The results indicated that feralolide might be a helpful memory restorative mediator in treating cognitive disorders such as Alzheimer’s disease.

Keywords: ABTS; DPPH; antiamnesic agent; elevated plus maze test; feralolide; scopolamine-induced mice.

Figure 1

Structure of feralolide.

Figure 2

Effect of feralolide (50, 100, and 200 mg/kg) in a short-term memory loss NORT. (A) exploration duration in sample phase, (B) exploration duration in test phase, (C) the discrimination index (DI). * p < 0.01. vs. the control group and * p, < 0.05, ** p. < 0.01 vs. the scopolamine 1 mg/kg.

Figure 3

Effects of the feralolide (50, 100, and 200 mg/kg) on scopolamine-induced cognitive/memory impairment in mice. Memory impairment was carried out by the administration of scopolamine at the dose of (1 mg/kg, i.p). (A) Mice escape latency in the hidden platform (tests for 6 consecutive days); (B) mice path length in the hidden platform tests (6 consecutive days); (C) mice frequency passing through hidden platform location. * p < 0.05; ** p < 0.01; against the scopolamine administered group. ## p < 0.01, ### p < 0.05; against the control group.

Figure 4

Effect of feralolide on learning and memory in EPM. Donepezil (2 mg/kg) was used as a standard drug. * p < 0.01 compared with control animals, # p < 0.0, ## p < 0.01 compared with scopolamine-treated animals. Values are mean ± SEM (n = 8), ANOVA followed by Tukey–Kramer test.

Figure 5

Effect of feralolide on the SDL in passive avoidance test. * p < 0.05 compared with scopolamine, # p < 0.05, ## p < 0.01, ### p < 0.001 compared with scopolamine. Value ranges are mean ± SEM (n = 8), ANOVA; followed by the Tukey–Kramer test. Donepezil (2 mg/kg) was used as a standard reference drug.

Figure 6

The compound is shown in the magenta ball and stick model; active site residues of enzymes are depicted in the green stick model, H-bonds are shown in black dotted lines, and hydrophobic interaction is displayed in light green dotted line. The binding mode of the compound is shown in the active sites of AChE (A) and BuChE (B).

Figure 6

The compound is shown in the magenta ball and stick model; active site residues of enzymes are depicted in the green stick model, H-bonds are shown in black dotted lines, and hydrophobic interaction is displayed in light green dotted line. The binding mode of the compound is shown in the active sites of AChE (A) and BuChE (B).