In Silico In Vitro and In Vivo Memory Enhancing activity of certain commercially available Flavonoids in Scopolamine and Aluminium Induced Learning Impairment in Mice

Abstract

Alzheimer s disease is a neurodegenerative disorder associated with a decline in cognitive abilities. The deficiency of acetylcholine is one of the characteristics of AD and responsible for most of its symptoms, such as a decline in memory and cognition. As a consequence of its role as a target for AD therapy, AChE is one of the most studied target in the Alzheimer s field and the vast majority of reports in the field relate with treatment strategies associated with the use of AChE inhibitors. Despite the severity and high prevalence of this disease, the allopathic system of medicine is yet to provide a satisfactory drug candidate. Hence, the present study was focused on exploration of the memory enhancing activity of the flavonoids in scopolamine and aluminium-induced learning impairment in mice. The current study suggests that the flavonoids, baicalein and scopoletin possessed excellent binding interactions and docking score with AChE and BuChE enzymes than the standard (donepezil) in in silico studies. The in silico studies addressed the flavonoids stability against AChE and BuChE (protein-ligand complex) by molecular dynamic simulation. The in silico studies is actually an added advantage to screen the ChE enzyme inhibition. Two hundred and forty five compounds were selected and screened in the computational studies and among these compounds 20 flavonoids have been selected for the in vitro enzyme inhibition studies based on their docking results. In conclusion, it has been clearly demonstrated that the approach utilized in this study is successful in finding novel anti-alzhiemer s drugs. In particular, higher dose of scopoletin and baicalein, showed excellent neuroprotective effects against in silico, in vitro enzyme inhibitory and in vivo acute scopolamine and chronic AlCl3 induced learning impairment models. Hence, scopoletin and baicalein could be considered as a therapeutic agent to prevent or slow down the development of neurodegenerative diseases such as AD. newline