Acetylcholinesterase inhibitors from southern African plants: An overview of ethnobotanical, pharmacological potential and phytochemical research including and beyond Alzheimer's disease treatment

Abstract

The review focuses on acetylcholinesterase (AChE) inhibition of extracts and compounds from southern African plants. We provide a detailed inventory of southern African plants used in the treatment of central nervous system (CNS) and memory-related disorders that are potential candidates for novel AChE inhibitors. This was achieved through a detailed literature search using web-based database searches including Google Scholar, Scopus and Web of Science (WoS) as well as ethnobotanical literature on southern African medicinal plants. Bibliometric analysis was performed on the data mined from WoS. In addition, we reviewed the methods used to determine AChE activity and highlighted the success and potential of alkaloids from the Amaryllidaceae. Our findings revealed about 200 southern African medicinal plants that are used for CNS and memory-related disorders. Approximately, 65 southern African plants have been evaluated for AChE inhibitory activity even though the majority of these plants do not have an ethnobotanical basis for such evaluation. Several extracts (e.g. Ammocharis coranica (KerGawl.) Herb., Lannea schweinfurthii Engl, Scadoxus puniceus (L.) Friis & Nordal, Xysmalobium undulatum (L.) W.T.Aiton.) have been found to demonstrate noteworthy (IC50 ≤ 1 μg/ml) AChE inhibitory activity. Moreover, 30 compounds have been isolated in an attempt to discover AChE inhibitors from southern African plants. The most active (IC50 ≤ 12 μM) compounds were isolated from Crinum moorei Hook. f., Scadoxus puniceus and Acacia nilotica (L.) Willd. ex Del. subspecies kraussiana (Benth.). Thus far, very few South African studies have looked at the ecological and environmental impact of both naturally occurring and applied AChE inhibitors (e.g. organophosphate and carbamate insecticides) and no studies have considered medical applications other than in Alzheimer's disease (AD) therapy. Furthermore, most of these studies have mainly used an in vitro approach directed at developing treatments of age-related dementia such as AD, despite the decline in pharmaceutical interest of AChE inhibitors in the treatment of AD. It is also apparent that no further steps are taken towards the investigation of in vivo studies and clinical trials. In addition to these existing gaps, the pharmacodynamic and pharmacokinetic studies also need to be adequately addressed in order to generate more coordinated and focused research.