Abstract

Embelin (2,5-dihydroxy-3-undecyl-1,4-benzoquinone) is one of the active components (2.3%) found in Embelia ribes Burm fruits. As determined via in vitro AChE inhibition assay, embelin can inhibit the acetylcholinesterase enzyme. Therefore, embelin can be utilized as a therapeutic compound, after further screening has been conducted for its use in the treatment of Alzheimer’s disease (AD). In this study, the nootropic and anti-amnesic effects of embelin on scopolamine-induced amnesia in rats were evaluated. Rats were treated once daily with embelin (0.3 mg/kg, 0.6 mg/kg, 1.2 mg/kg) and donepezil (1 mg/kg) intraperitoneally (i.p.) for 17 days. During the final 9 days of treatment, a daily injection of scopolamine (1 mg/kg) was administered to induce cognitive deficits. Besides that, behavioral analysis was carried out to assess the rats’ learning and memory functions. Meanwhile, hippocampal tissues were extracted for gene expression, neurotransmitter, and immunocytochemistry studies. Embelin was found to significantly improve the recognition index and memory retention in the novel object recognition (NOR) and elevated plus maze (EPM) tests, respectively. Furthermore, embelin at certain doses (0.3 mg/kg, 0.6 mg/kg, and 1.2 mg/kg) significantly exhibited a memory-enhancing effect in the absence of scopolamine, besides improving the recognition index when challenged with chronic scopolamine treatment. Moreover, in the EPM test, embelin treated rats (0.6 mg/kg) showed an increase in inflection ratio in nootropic activity. However, the increase was not significant in chronic scopolamine model. In addition, embelin contributed toward the elevated expression of BDNF, CREB1, and scavengers enzymes (SOD1 and CAT) mRNA levels. Next, pretreatment of rats with embelin mitigated scopolamine-induced neurochemical and histological changes in a manner comparable to donepezil. These research findings suggest that embelin is a nootropic compound, which also possesses an anti-amnesic ability that is displayed against scopolamine-induced memory impairment in rats. Hence, embelin could be a promising compound to treat AD.

Highlights

  • Alzheimer’s disease (AD) is known as the leading cause of dementia amongst people aged 65 and older (Ghumatkar et al, 2015)

  • The findings of this study showed that embelin at 0.6 mg/kg displayed nootropic activity in both the recognition index and inflection ratio in the novel object recognition (NOR) and elevated plus maze (EPM) tests, respectively (Figures 2A,B)

  • The results from this study have demonstrated that embelin displays nootropic and neuroprotective abilities in scopolamine-induced amnesia in rats

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Summary

Introduction

Alzheimer’s disease (AD) is known as the leading cause of dementia amongst people aged 65 and older (Ghumatkar et al, 2015). This age-related disease affects millions of individuals, and it is estimated that by 2050, 1 in 85 people worldwide will be suffering from AD (Brookmeyer et al, 2007). The key features of AD’s pathogenesis are the gradual amassing of the protein fragment beta-amyloid (plaques) and twisted fibers of the protein tau (tangles), outside and inside neurons in the brain, respectively (Alzheimer’s Association, 2017). Tau tangles prevent the passage of essential molecules and nutrients inside neurons, which causes axonal transport dysfunction and neuronal loss (Ali et al, 2015; Alzheimer’s Association, 2017)

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