In-silico and in-vitro correlation studies of natural β-secretase inhibitor: An approach towards Alzheimer’s disease

Alzheimer’s disease (AD) is one among the common type of dementia in elder people above the age group of 65 years. This was once considered a rare disorder but in recently was considered as a great threat and risk factor to the elderly community above 60 years. AD is also considered a highly prevalent neurodegenerative disease. AD is characterized by loss of neuron and disturbed signal between cells in the brain. The neurotransmitter deficit is discovered in AD include acetylcholine (ACh). The major pathophysiological character of AD are the accumulation of extracellular neuritic plaques and neurofibrillary tangles in brain specially located in the memory related areas. The neuritic plaques are composed of β-amyloid peptide with 40 to 42 residues, on hydrolysis of amyloid precursor protein (APP) by the β-secretase 1 (BACE-1). Inhibition of β-secretase is one of the most promising treatment for AD. Ayurveda is one of the oldest system of medicine which is practiced till today and is gaining importance due to its unique principles and usage of many crude drugs for memory related disorders. Ashwagandha and pepper widely used in Ayurveda, in the present work molecular modelling techniques such as extra precision docking of natural BACE inhibition and in-vitro β-secretase inhibition assay was done on withanolide and piperine. Both the natural marker compounds showed promising inhibitory activity and proved the potential in treating memory related disorders.