Effect of Ellagic Acid on Streptozotocin Induced Alzheimer's Disease in Rats

Abstract

Alzheimer’s disease is a type of neuro degenerative disorder leading to memory and other senile function loss. Epidemiology suggests that in 2015, 46.8 million people were suffering from dementia and its growth is said to increase by 2 fold every 20 years. A range of medicine like donepezil, galantamine, rivastigmine and memantine has been approved by USFDA in treatment of Alzheimer’s disease but they only try to inhibit further growth of some biochemical but could not alter the progression of disease. These drugs can produced symptomic relief but can non inhibit further progression of disease. Moreover, many herbal drugs have been identified to have significant activity on Alzheimer’s disease like curcumin, cinnamon oil, ellagic acid, green tea, garlic, ferulic acid, paclitaxel, vitamin E and Vitamin B12. Ellagic acid have been found as active constituent in cranberry, raspberry, pomegranate, walnuts and many more. It is reported for anti-oxidant and anti-inflammatory. Thus, present study was planned to study effect of ellagic acid on Alzheimer’s disease. Material and Methods Alzheimer’s was induced by help of streptozotocin (3 mg/kg) via intracerebroventricular incision near bregma, with single dose and rats were further sutured. Group-1 consisted of normal control with no surgery and no dosage, group-2 was disease control group (STZ-icv) no dosage, group-3 was sham control group with only vehicle, group-4 was positive control (STZ+Donepezil (DONO)) at dose of 4.2 mg/kg, group 5 treatment control 1 (STZ+ellagic acid(E1)) at dose of 25mg/kg and group 6 consisted of treatment control 2 (STZ+ellagic acid (E2)) 50 mg/kg. Furthermore, rats were given training on Y-maze and Radial arm maze to check the change in the behavioral pattern and were accessed once a week till 5 weeks. Rats were sacrificed on 35th day with isolation of brain and blood to check biochemical and histopathological changes. Result The behavioral change was observed in Y-maze for the spontaneous alteration score with significantly (p<0.05) decreased in diseased control group as compared to normal control group while in STZ+DONO, STZ+E1 and STZ+E2 there was significant (p<0.05) increase in alteration score as compared to disease control group. Moreover, the total arm entry in Y-maze showed significant (p<0.05) decreased in diseased control group as compared to normal control group while in STZ+DONO, STZ+E1 and STZ+E2 there was significant (p<0.05) increase as compared to disease control group. The radial arm maze shows working memory of animal by the correct arm entry and total arm entry. The total arm entry in radial arm maze showed significant (p<0.05) decrease in diseased control group as compared to normal control group while in STZ+DONO and STZ+E2 there was significant (p<0.05) increase as compared to disease control group shows a significant decrease in total arm entry. While, the total arm entry showed significant (p<0.05) decrease in diseased control group as compared to normal control group while in STZ+DONO, STZ+E1 and STZ+E2 there was significant (p<0.05) increase as compared to disease control group. Moreover, from the isolated blood, serum was separated and C-reactive protein was estimated and a significant (p<0.05) increase in diseased control group was observed as compared to normal control group while in STZ+DONO, STZ+E1 and STZ+E2 there was significant (p<0.05) decrease as compared to disease control group. Furthermore, in biochemical estimation brain was homogenized and supernatant was extracted to perform assay. A significant (p<0.05) increase in diseased control group was observed as compared to normal control group while in STZ+DONO, STZ+E1 and STZ+E2 there was significant (p<0.05) decrease as compared to disease control group for acetylcholine-esterase assay. Also in brain mitochondrial ATPase assay a significant (p<0.05) decreased in diseased control group as compared to normal control group while in STZ+DONO, STZ+E1 and STZ+E2 there was significant (p<0.05) increase in levels as compared to disease control group. A significant (p<0.05) increase in diseased control group was observed as compared to normal control group while in STZ+DONO, STZ+E1 and STZ+E2 there was significant (p<0.05) decrease as compared to disease control group for lipid peroxidation and superoxide dismutase assay. On contrary in reduced glutathione, catalase and total protein assay a significant (p<0.05) decreased in diseased control group as compared to normal control group while in STZ+DONO, STZ+E1 and STZ+E2 there was significant (p<0.05) increase in levels as compared to disease control group. A histopathological change in the hippocampus was observed with damaged cells in disease induced group while normal and treated group showed lesser damage. Conclusion Animals treated with Ellagic acid were showed the decline in the progression of neurodegeneration by STZ induced AD. In AD main symptoms is loss of memory, in the ellagic acid treated animals have improved memory estimated by behavioral study. In that reduced antioxidant properties by reduced the level of SOD, MDA and increased the level of catalase in the treated animals with ellagic acid. AD is also associated with excess loss of cholinergic neurons but in group of ellagic acid, decreased the AChE level in the brain that increased function and energy metabolism. In the AD the decreased the level of glutathione by the excitotoxicity but in the ellagic acid treated animal have increased the level of glutathione and protection against of excitotoxicity. Ellagic acid showed protective effect against streptozotocin induced Alzheimer’s disease which is reflected as improvement in spatial and working memory, maintenance of strong neuronal connectivity. The effect might be due to reduced inflammation, oxidative stress and inhibition of the acetylcholinesterase enzyme. However, studies are required to explore the possible molecular mechanisms, chronic toxicity and to develop its optimized dosage form to present it as the potential candidate for clinical studies for treatment of neuro degenerative disorders.