Abstract

Oxidative stress is usually associated with many neurodegenerative diseases. In this study, the gas chromatography–mass spectrometry (GC–MS) analysis of cold-pressed oil (CPO) from black pepper (Piper nigrum) fruits was performed and its neuroprotective effects were evaluated for the first time. The analysis of CPO revealed the presence of the lignan sesamin (39.78%), the alkaloid piperine (33.79%), the monoterpene hydrocarbons 3-carene (9.53%) and limonene (6.23%), and the sesquiterpene β-caryophyllene (10.67%). Black pepper hydrodistilled oil (HDO) was also comparatively analyzed by GC–MS to show the impact of oil isolation by two different methodologies on their components and class of compounds identified. HDO analysis revealed 35 compounds (99.64% of the total peak areas) mainly composed of monoterpene hydrocarbons (77.28%), such as limonene (26.50%), sabinene (21.36%), and β-pinene (15.53%), and sesquiterpene hydrocarbons (20.59%) represented mainly by β-caryophyllene (19.12%). Due to the low yield obtained for HDO (0.01% v/w), only CPO was chosen for the evaluation of its neuroprotective potential. Alzheimer-type dementia was induced in rats by scopolamine intraperitoneal injection (1.5 mg/kg/day) for seven days. CPO was administered orally (100 mg/kg) for a week before scopolamine administration and then concomitantly for another week. Donepezil (1 mg/kg, orally) was used as a reference drug. CPO administration significantly improved the rat behaviors as evaluated by the Morris water maze test, evident from prolongation in time spent in the platform quadrant (262.9%, compared to scopolamine) and increasing in the crossing time by 18.18% compared to the control group. The rat behavior tested by passive avoidance, showed prolongation in the step-through latency compared to control. Moreover, CPO significantly (p < 0.05) ameliorated the activities of antioxidant enzymes such as catalase, superoxide dismutase (SOD) and reduced malondialdehyde (MDA) equivalents by 22.48%, 45.41%, and 86.61%, respectively, compared to scopolamine. Furthermore, CPO administration decreased scopolamine-induced elevated acetylcholinesterase levels in rats’ hippocampi by 51.30%. These results were supported by histopathological and in silico molecular docking studies. Black pepper oil may be a potential antioxidant and neuroprotective supplement.

Highlights

  • Alzheimer’s is a progressive disease with estimated prevalence of about 47 million individuals worldwide

  • The aim of the present study was to evaluate of the neuroprotective effects of black pepper cold-pressed oil (CPO) against scopolamine-induced oxidative stress and memory impairments in rats, together with identifying its bioactive components via gas chromatography–mass spectrometry (GC–MS) analysis for the first time

  • Prolonged escape latency was observed in the scopolamine-treated group rats, in addition to a marked shortening of time spent in the platform quadrant with a percentage decrease of 84% compared to the control group

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Summary

Introduction

Alzheimer’s is a progressive disease with estimated prevalence of about 47 million individuals worldwide. It is characterized by neurodegeneration of the brain tissues, impairment of memory capabilities, decreased levels of acetylcholine and disturbance of behavior [1,2,3,4]. Treatment protocols usually involve cholinesterase inhibitors, such as donepezil, galantamine, and rivastigmine, for mild to moderate cases, while patients demonstrating much severe cases can be administered N-methyl-D-aspartate receptor antagonists, such as memantine. Many AChE inhibitors are used for symptomatic treatment of Alzheimer’s. These inhibitors are non-selective and demonstrate cholinergic and hepatotoxic adverse effects. There is an increased need and global attention to the search for a safer management through herbal supplements and natural phytochemicals [6,7]

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