Advances on plant extracts and phytocompounds with acetylcholinesterase inhibition activity for possible treatment of Alzheimer's disease

Background: Alzheimer's disease (AD) is a neurodegenerative disease caused by the formation of amyloid-beta (Aβ) plaques and neurofibrillary tangles. Acetylcholinesterase (AChE), a serine hydrolase, is the crucial enzyme in the hydrolysis of one of the most extensively known neurotransmitters acetylcholine (ACh) that has been associated with the pathophysiology of AD. From this perspective, enzymatic inhibition of AChE activity has been an auspicious treatment strategy for AD. Different natural products extracted from various plant sources have begun to gain popularity worldwide as a potential inhibitor of acetylcholinesterase (AChEi), and thus, could be used as a therapeutic option for AD treatment. Purpose: The present study congregates and discusses the hitherto scattered data of medicinal plants used for the treatment of AD worldwide. The already existing drugs of AD have been discussed. This study aims to highlight species with assessed efficacy, usable tissues, model organisms, and extraction information, to point out species of interest for further study. A critical assessment and examination of plants were done for the potential pharmacological evaluations. Materials and methods: This review surveys all the published literature (research and review articles) between 2000 and 2021 using numerous search engines and publication houses viz. Web of Science, PubMed, ScienceDirect, Springer, Google scholar, Taylor and Francis imprints, Chemspider, Wiley and NCBI (National center for Biotechnology Information). The literature search was conducted using the following keywords in different combinations: acetylcholinesterase inhibitors, plant extract and Alzheimer disease. More than 300 studies were recovered from which 107 were considered final summarization. Latin names of the identified plant species were validated at The Plant List (2013); version 1.1.; http://www.theplantlist.org/ (accessed 15th August 2018). Results: A bulk amount of research has revealed a comprehensive inventory of plant-based acetylcholinesterase inhibitors to date. Due to the lack of promising, effective, and safe inhibitors, this broad array of phytochemicals has captured the focus of research on the inhibition-based treatment of AD. From the literature search, sixteen plant species were found to have high potency with IC50 values ranging from 0.08 µg/mL to 18.9 µg/mL. Conclusion: This review broadly discusses the existing approved drugs against AD along with natural products extracted from several plant sources with potential AChEi. Species with higher AChEi potency could be evaluated further for pharmacological application.