Glabridin from Glycyrrhizha glabra Linn. as multi-targeted therapeutic agent against Alzheimer’s disease: an in-silico study

Alzheimer’s disease (AD) is a progressive neurodegenerative disease mainly occurring in old age adults. Its pathophysiology involves accumulation of tau protein in brain leading to the intracellular neurofibrillary tangles (NFTs) and amyloid β protein accumulation leads to extracellular amyloid β plaques in the central nervous system. Existing treatments for such neurodegenerative conditions do not slow-down disease progression, and this will cause an overwhelming future burden on our healthcare system and immense suffering for many more patients and their families. The current researches for developing potential drugs for the Alzheimer’s disease mainly focusing on the therapeutic targets such as acetylcholine esterase (AChE), Butrylcholine esterase (BuChE), β-site APP-cleaving enzyme1 (BACE1), Glycogen synthase kinase-3β (GSK3β) and Kelch-like ECH Associated Protein 1 (Keap1). To halt the progression of the disease, discovery of the molecules that potentially interferes with these therapeutic targets is paramount important. The ADMET property analysis showed that 5 flavonoid compounds from the plant Glycyrrhiza glabra Linn. were biologically active with drug-likeliness nature. The molecular docking and molecular dynamic simulation studies evidenced that among these phytochemicals glabridin can be a potential inhibitor of the Alzheimer’s therapeutic target proteins AChE, BuChE, BACE-1, GSK3β and Keap1. This may have a role in controlling the pathogenesis and thereby curing the disease. Further in vivo investigations is required to validate the compound as a new therapeutic agent for the Alzheimer’s disease.