Ameliorative Treatment with Ellagic Acid in Scopolamine Induced Alzheimer’s Type Memory and Cognitive Dysfunctions in Rats

Research Article

Austin J Clin Neurol 2015;2(6): 1053.

Ameliorative Treatment with Ellagic Acid in Scopolamine Induced Alzheimer’s Type Memory and Cognitive Dysfunctions in Rats

Ramandeep Kaur, Sidharth Mehan*, Deepa Khanna and Sanjeev Kalra

Department of Pharmacology, Rajendra Institute of Tech & Sciences, India

*Corresponding author: Sidharth Mehan, Associate Professor, Department of Pharmacology, Rajendra Institute of Tech & Sciences, Sirsa-125055, Haryana, India

Received: March 19, 2015; Accepted: May 14, 2015; Published: May 29, 2015


Objective: To determine neuroprotective effects of Ellagic acid (EA) as a preventive herbal drug to impede cholinergic dysfunctions and oxidative stress in Alzheimer’s disease (AD) in scopolamine induced Alzheimer’s type dementia in rats.

Methodology: Alzheimer’s type dementia was induced by intraperitoneal injection of scopolamine (0.7 mg/kg, i.p.) to rats for period of 7 days. EA (25 mg/kg or 50 mg/kg, p.o.) or Donepezil (0.5 mg/kg, p.o.) alone was treated for 6 days and then scopolamine (0.7 mg/kg, i.p.) was administered together with EA or Donepezil for another 7 days. Memory-related behavioral parameters were evaluated using the elevated plus maze (EPM) once a day for 2 consecutive days and Morris water maze (MWM) once a day for 5 consecutive days. At the end of protocol schedule i.e day 14, biochemical parameters were estimated. AChE, MDA, GSH, catalase and SOD to evaluate the neuroprotective action of EA via AChE inhibition and antioxidant activity.

Result: Scopolamine treatment increased the transfer latency in EPM, escape latency time and shortened time spent in the target quadrant in MWM; these effects were reversed by EA. Scopolamine-mediated changes in malondialdehyde (MDA) and AChE activity were significantly attenuated by EA in rats. Recovery of antioxidant capacities, including reduced glutathione (GSH) content, and the activities of SOD and catalase was also evident in EA treated rats.

Conclusion: The present findings sufficiently encourage that EA has a preventive properties. Although EA was found to be less effective than Donepezil, but few modification in pharmaceutical properties it can be an efficient phytochemical for Alzheimer type dementia. The EA can be used to prevent cholinergic dysfunctions and oxidative stress associated with Alzheimer type dementia.

Keywords: Neuroinflammation; Oxidative stress; Acetylcholinesterase; Polyphenols


Alzheimer’s disease (AD) is a severe neurodegenerative disorder that gradually results in loss of memory and impairment of cognitive functions in the elderly [1,2].

Many naturally occurring compounds have been proposed as potential therapies to slow or prevent the progression of AD, mostly by acting as antioxidants [3-5], but also with some direct anti-amyloid actions [6-8]. Recent studies have suggested the positive effects of dietary antioxidants as an aid in potentially reducing somatic cell and neuronal damage by free radicals [3,9,10]. The beneficial health effects of plant-derived products have been largely attributed to polyphenolic compounds, as well as vitamins, minerals and dietary fibers [3,4,11].

Ellagic acid (EA), a non flavonoid polyphenol, plays an essential role in explaining the pharmacological properties of fruits, food and beverages which exhibit this phyto-constituent [12-14]. EA has been well proven to contain anti-oxidant [15-17], anti-inflammatory [18,19], anti-proliferative [20-22], antidiabetic [23,24] and cardioprotective [25,26] properties.

Neuroprotection can be a property of EA as it prevents both neuro-oxidation and neuroinflammation [27-30]. Moreover, in invitro studies it was observed that EA inhibits β-secretase (BACE1), thus inhibiting Aβ-fibrillation and decrease AChE activity [31- 33]. Recent studies suggested that glucose metabolism is affected during AD [34]. The EA stimulated GLUT4 translocation primary factor responsible for insulin induced glucose uptake and maintain glucose homeostasis [35,36]. The EA also shows modulation of monoaminergic system (serotonergic and noradrenergic systems) and GABAnergic system [37,38]. Cognitive impairment in AD patients correlates with disturbance in various neurotransmitters, as the ratio of excitatory-inhibitory neurotransmitter level disturbs, cytotoxic damage to neurons and glia occurs and norepinephrine and serotonin levels declined [39-43]. Further, Gamma-amino butyric acid (GABA) increases the formation of soluble receptor for advanced glycation end products (RAGE) and decreases the levels of full-length RAGE, lowering the Aβ uptake and inflammatory mediated reactions [44,45].

Scopolamine, an anti-muscarinic agent, competitively antagonizes the effect of acetylcholine on the muscarinic receptors by occupying postsynaptic receptor sites with high affinity and increases AChE activity in the cortex and hippocampus [46-50]. Scopolamine diminish cerebral blood flow due to cholinergic hypofunction [51,52]. Scopolamine additionally triggers ROS, inducing free radical injury and an increase in a scopolamine-treated group brain MDA levels and deterioration in antioxidant status [53-55]. Scopolamine induces neuro-inflammation by promoting high level of oxidative stress and pro inflammatory cytokines in the hippocampus [56- 58]. Scopolamine is proven to increase levels of APP and Tau. Administration of scopolamine led to marked histopathological alterations in the cerebral cortex, including neuronal degeneration [59,60]. Scopolamine administration has been used both in healthy human volunteers and in animals as a model of dementia to determine the effectiveness of potential new therapeutic agents for Alzheimer’s disease [61-66] (Figure 1).