Cholinergic phytochemicals: From magic to medicine

Abstract

The decline in cortical cholinergic activity in aging and degenerative diseases associated with dementia is, in conjunction with increasing genetic and molecular complexity, one of the most consistent observations in psychopathology. Numerous plants synthesize compounds, interacting with cholinergic systems which have been of value in exploring the role of the cholinergic system in aging and dementia. These chemicals deter predators by interfering with autonomic, central nervous or neuromuscular systems. The original hypothesis that memory loss in Alzheimer's disease relates to a central cholinergic deficiency was partly based on the experimental induction of related cognitive impairments in normal individuals exposed to the naturally occurring muscarinic antagonist scopolamine. Long before this, in ancient Greece, henbane (containing alkaloids such as atropine and scopolamine) was used to mimic 'dementia' and provoke prophesy. The tendency of such tropane alkaloids to induce hallucinations is consistent with low neocortical activities and the high incidence of psychotic features in Dementia with Lewy bodies (DLB). Other plant derived alkaloids such as physostigmine and galanthamine, inhibiting acetylcholinesterase, are among those including the synthetic chemical tacrine, being tested in dementia therapy. Cognitive enhancement, although significant, is limited and antipsychotic effects may be more prominent. The recent discovery of brain nicotinic receptors and the neuroprotective role of the tobacco alkaloid nicotine provides a further dimension to cholinergic therapy in retarding the neurodegenerative process. The potential for new cholinergic drug development based on the rich biodiversity of plant chemicals and principles of ethnobotany, in the context of modern pharmacology, is still largely unexplored in age-related mental disorders. Several plant species reputed to improve memory in European medicinal plant encyclopaedias have cholinergic activities which may be therapeutically relevant.