Cognitive Facilitation and Antioxidant Effects of an Essential Oil Mix on Scopolamine-Induced Amnesia in Rats: Molecular Modeling of In Vitro and In Vivo Approaches

Abstract

The present study investigated the capability of an essential oil mix (MO: 1% and 3%) in ameliorating amnesia and brain oxidative stress in a rat model of scopolamine (Sco) and tried to explore the underlying mechanism. The MO was administered by inhalation to rats once daily for 21 days, while Sco (0.7 mg/kg) treatment was delivered 30 min before behavioral tests. Donepezil (DP: 5 mg/kg) was used as a positive reference drug. The cognitive-enhancing effects of the MO in the Sco rat model were assessed in the Y-maze, radial arm maze (RAM), and novel object recognition (NOR) tests. As identified by gas chromatography–mass spectrometry (GC–MS), the chemical composition of the MO is comprised by limonene (91.11%), followed by γ-terpinene (2.02%), β-myrcene (1.92%), β-pinene (1.76%), α-pinene (1.01%), sabinene (0.67%), linalool (0.55%), cymene (0.53%), and valencene (0.43%). Molecular interactions of limonene as the major compound in MO with the active site of butyrylcholinesterase (BChE) was explored via molecular docking experiments, and Van der Waals (vdW) contacts were observed between limonene and the active site residues SER198, HIS438, LEU286, VAL288, and PHE329. The brain oxidative status and acetylcholinesterase (AChE) and BChE inhibitory activities were also determined. MO reversed Sco-induced memory deficits and brain oxidative stress, along with cholinesterase inhibitory effects, which is an important mechanism in the anti-amnesia effect. Our present findings suggest that MO ameliorated memory impairment induced by Sco via restoration of the cholinergic system activity and brain antioxidant status.

Cotinine and 6-Hydroxy-L-Nicotine Reverses Memory Deficits and Reduces Oxidative Stress in Aβ25-35-Induced Rat Model of Alzheimer’s Disease

“…Short-term spatial recognition memory and locomotor activity were assessed using a single-session Y-maze test, which was previously described by Jackson [ 45 ] and Boiangiu et al [ 46 ]. The apparatus was made from black Plexiglas and consisted of three identical arms with a size of 35 × 10 × 25 cm (L × l × h) joined in a central area in the form of an equilateral triangle shape.…”

“…The novel object recognition (NOR) protocol uses the natural preference of the rodents for novel objects and is used to evaluate the cognitive modifications in rodent models of neurodegenerative disorders [ 47 ]. The rodents were trained and tested according to the procedure described previously by Foyet et al [ 48 ] and Boiangiu et al [ 46 ]. The test apparatus consisted of a black square-shaped box made from wood of the size 72 × 72 × 36 cm (L × l × h).…”

Bay Leaf (Laurus Nobilis L.) Incense Improved Scopolamine-Induced Amnesic Rats by Restoring Cholinergic Dysfunction and Brain Antioxidant Status

“…DP (5 mg/kg, Sigma-Aldrich, Darmstadt, Germany) and Sco (0.7 mg/kg, Sigma-Aldrich, Darmstadt, Germany) were dissolved in 0.9% physiological saline and i.p. injected, once daily, 30 min before the Y-maze, the novel object recognition and the radial arm-maze tests [27].…”

“…Behavioral Assessments 2.6.1. Y-Maze Spontaneous Alternation Test Short-term spatial memory was assessed by recording spontaneous alternation behavior in a single-session Y-maze as previously described by Jackson [29] and Boiangiu et al [27]. At 5 min after BL inhalation, each rat was placed at the end of one arm and allowed to explore the Y-maze freely for 8 min.…”

“…The radial arm-maze test (RAM) was used to explore working memory as well as reference memory for 5 min session after inhaling the BL as previously described by Olton and Samuelson [30] and Boiangiu et al [27]. ANY-maze ® software (Stoelting CO, Wood Dale, IL, USA) was used to record the movements of rats inside the RAM.…”