Natural Inhibition of β-secretase in Alzheimer’s Disease by Medicinal Plants

Abstract

Alzheimer’s disease (AD) is the most common type of dementia, an irreversible neurodegenerative disease that worsens over time. It frequently affects the elderly population and, therefore, its prevalence is soaring in countries with a high proportion of the aging population. The incidence of AD is likely to increase further with increasing life expectancy throughout the world. There is still no sight of therapies that could stop or slow the progression of AD despite the significant expansion in our understanding of the disease at molecular, cellular, and system levels in the last 50 years. The only medications approved by the Food and Drug Administration (FDA), for the treatment of AD are acetylcholinesterase inhibitors (donepezil, galantamine, tacrine, and rivastigmine) and glutamate receptor antagonist (memantine). Apart from acetylcholinesterase inhibition, another important therapeutic target for treating AD is the inhibition of β‐site APP cleaving enzyme‐1 (BACE1), which is involved in the proteolysis of the amyloid precursor protein (APP) leading to the formation of neurotoxic amyloid β (Aβ) protein. Extensive research following this approach has led to the rationally designed synthetic, and potent BACE1 inhibitors, several of which are in clinical trials. However, the high failure rate of the BACE1 inhibitors in clinical trials necessitates finding a different source of BACE1 inhibitors. In this review, we discuss the most promising phytocompounds and plant extracts showing potent BACE1 inhibitory activity. Future research directions are suggested and recommendations are made to expand the use of medicinal plants and their formulations to prevent, mitigate and treat AD.