Essential oils as potential acetylcholinesterase and butyrylcholinesterase inhibitors. A case study: Elettaria cardamomum (L.) Maton essential oil

Alzheimer’s disease (AD) is the most common dementia of old age worldwide, characterized by extensive neuronal death that occurs over time and in an irreversible manner. To the best of our knowledge, there is no treatment that can affect the progression of the disease. There are only symptomatic drugs that improve the patient's cognitive abilities and attempt to prevent the progression of the disease. These drugs are acetylcholinesterase (AChE) inhibitors such as donepezil, rivastigmine and galantamine, but in the late stages of AD, butyrylcholinesterase (BChE) levels increase significantly, while AChE levels decrease in the hippocampus and temporal cortex. Therefore, it is important to find effective BChE inhibitors that raise acetylcholine (ACh) levels in advanced AD to prevent the negative effects of AChE suppression. Inhibitors of both types of cholinesterase have recently gained popularity in AD drug discovery and are indeed one of the avenues being pursued for AD research. Essential oils (EOs), complex mixtures of hundreds of compounds, have traditionally been used to improve cognitive abilities and alleviate other symptoms associated with AD; in addition, their complexity in terms of bioactive molecules makes them an ideal target for research into inhibitors of these enzymes. Sixty-nine essential oils from different plant species and botanical families (Annonaceae, Apiaceae, Asteraceae, Betulaceae, Burseraceae, Caryophyllaceae, Compositeae, Cupressaceae, Ericaceae, Geraniaceae, Lamiaceae, Lauraceae, Mirtaceae, Oleaceae, Pinacee, Piperaceae, Poaceae, Rosaceae, Rutaceae, Santalaceae, Stiracaceae, Verbenaceae, Zingiberaceae) were subjected toAChE and BChE in vitro colorimetric assay by the Ellman method and chemically characterized using gas chromatography coupled to mass spectrometry. Several essential oils were found to be potential AChE or BChE inhibitors, but the only EO that was found to be active in inhibiting both enzymes was Elettaria cardamomum (L.) Maton essential oil. Therefore, the study focused on finding specialized bioactive metabolites in this particular essential oil. E. cardamomum is a plant that belongs to the Zingiberaceae family and has been used for centuries in traditional Ayurvedic and Chinese medicine for a variety of different purposes in the form of infusions, decoctions, distillates and essential oils. The rapid spread of the use of the essential oil of this plant throughout the world and its use in food, medicine, and fragrance development makes it a very interesting matrix in the research of specialized bioactive metabolites. A bio-guided fractionation approach was used to isolate fractions/pure compounds that can be tested individually to evaluate their activity. E. cardamomum EO hydrocarbon fraction was found to be inactive towards both AChE and BChE; conversely, the oxygenated fraction was active towards both enzymes. These results demonstrate that the essential oil of E. cardamomum is a promising source of potential AChE and BChE inhibitors.