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.
Highlights
Neurodegeneration can be defined as forfeiture of neuron structure and function in a progressive way, which is associated with various diseases such as Alzheimer’s disease (AD), Parkinson’s disease, Huntington disease, amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), etc. [1]
The MO formulated for motivation and enhancing mood was analyzed by gas chromatography–mass spectrometry (GC–MS)
The MO tested was expected to contain limonene as the leading component as limonene is well-known to be the major monoterpene in Citrus essential oils, which was confirmed by our analysis
Summary
Neurodegeneration can be defined as forfeiture of neuron structure and function in a progressive way, which is associated with various diseases such as Alzheimer’s disease (AD), Parkinson’s disease, Huntington disease, amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), etc. [1]. Based on the cholinergic hypothesis approach, the most prescribed drug class against the disease is AChE inhibitors, as an apparent deficit in acetylcholine (ACh) is shown to occur in the brains of AD patients. Inhibition of AChE is suggested to be a promising strategy [3], which restores the memory deficits in AD patients. Despite repeated failures in the formulation of preventive and disease-modifying therapies, the AChE inhibitors appear to play a crucial role in controlling the symptoms and potentially slowing the rate of AD progression [4]. Research suggested that people with mild cognitive impairment (MCI) and dementia exhibited an increased risk of developing anxiety and depression as compared to people with normal cognitive function [5]. It has been demonstrated that oxidative stress is a pivotal factor to the progression of AD through three pathways: macromolecule peroxidation, amyloid-beta (Aβ) metal ion redox potential, and mitochondrial dysfunction, all of which affect cell homeostasis, the generation of reactive oxygen species (ROS), and the up-regulation of Aβ and p-tau formation [6]
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