Evaluation OF Effect of Cow Ghee Curcumin Combination in AICI3 Induced Neuroadegeneration

Abstract

BACKGROUND AND OBJECTIVES Alzheimer’s disease is a progressive neurodegenerative disorder, characterized by deterioration of cognitive function and accumulation of Amyloid-β plaques and neurofibrillary tangles, which may eventually progress to physical impairment and death. It is the fifth leading cause of mortality and morbidity. For ease and better control on AD we need multi-targeted drug therapy. Intranasal treatment of Cow ghee and Curcumin mixture has been selected to avoid side effects of any newer chemical entity and wider acceptability of herbal and traditional compound. The purpose for the selection of intranasal route of administration is for the direct nose to brain delivery of the drug through olfactory bulb. The objective of this study is to evaluate the effect of Cow ghee - Curcumin combination in AlCl3 induced neurodegeneration in rats. MATERIALS AND METHODS In present study protocol animals acclimated in standard controlled condition in animal house were divided in 6 groups as Normal control (NC), Disease control (AlCl3 - 17 mg/kg, oral) (DC), Donepezil treated (DD) (5 mg/kg, oral), Cow Ghee treated (DCG) (Intranasal), Curcumin treated (DCur) (10 mg/kg, intranasal) and Cow Ghee+Curcumin treated (DCCur) (10 mg/kg) groups. The animals were given behavioural training on Y-maze for five days before disease induction. Disease induction was started with simultaneous treatment according to the group division for 4 successive weeks. Y-maze and water maze were utilized for the evaluation of neurobehavioral parameters. After evaluation of behavioural paradigms animals were sacrificed and the brains were collected. The brains were utilized to evaluate various oxidative stress parameters, brain Acetylcholinesterase level, ELISA for various biomarkers (i.e., Amyloid β, p Tau) of Alzheimer’s disease and histopathological changes evaluation in brain tissue. RESULTS Neurobehavioral studies. Treated group animals were observed for increased total arm entry and percentage alternation score in Y-maze when compared with DC group which indicates improvement in locomotive behaviour, spatial working memory and exploration behaviour of animals. In water maze animals were observed for the improvement in escape latency test and after removal of hidden platform, treated animals were observed for improvement in probe trial test of water maze when compared with DC group which indicates improvement in spatial recognition memory. Biochemical Parameters There was reduction in Amyloid β and p Tau in Cow Ghee + curcumin treated group as compared to DC group. Oxidative stress of treated group animals was also reduced according to various oxidative stress parameters like SOD, GSH, MDA and catalase. As well as brain Acetylcholinesterase level of treated group was found to be reduced compared to DC group animals. Histopathological studies Histopathological study depicted marked neurodegeneration in brain hippocampal region of DC group animals when compared with NC group. And the treated group illustrated improvement in cellular arrangement as well as morphology of neurons. CONCLUSION The proposed drug combination showed improved locomotive activity, spatial working memory, spatial recognition memory and reduced oxidative stress as well as reduced AchE in treated animals. There was decrease in Amyloid β and p Tau has been observed, which is the most important biomarker for AD. From the results we can conclude that intranasal administration of cow ghee and curcumin mixture have potency to prevent Alzheimer’s Disease and it works as a good combination for prevention of disease with minimal side effects. Following study needs further investigation and it has future scope to prevent Alzheimer’s disease in humans.