Abstract
Finding a new type of cholinesterase inhibitor that would overcome the brain availability and pharmacokinetic parameters or hepatotoxic liability has been a focus of investigations dealing with the treatment of Alzheimer’s disease. Isothiocyanates have not been previously investigated as potential cholinesterase inhibitors. These compounds can be naturally produced from their glucosinolate precursors, secondary metabolites widely distributed in our daily Brassica vegetables. Among 11 tested compounds, phenyl isothiocyanate and its derivatives showed the most promising inhibitory activity. 2-Methoxyphenyl ITC showed best inhibition on acetylcholinesterase with IC50 of 0.57 mM, while 3-methoxyphenyl ITC showed the best inhibition on butyrylcholinesterase having 49.2% at 1.14 mM. Assessment of the antioxidant efficacy using different methods led to a similar conclusion. The anti-inflammatory activity was also tested using human COX-2 enzyme, ranking phenyl isothiocyanate, and 3-methoxyphenyl isothiocyanate as most active, with ∼99% inhibition at 50 μM.
Highlights
Alzheimer’s disease is the most common neurodegenerative disorder in western societies, mostly affecting elderly population
11 commercially available ITCs were tested for their cholinesterase inhibitory, and antioxidant activities as well as anti-inflammatory activity via PGE-2 synthesis suppression through COX-2 inhibition
Rancimat assay Fish oil was investigated using a Rancimat 743 (Metrohm, Herisau, Switzerland) instrument in order to monitor the progress of accelerated oxidation
Summary
Alzheimer’s disease is the most common neurodegenerative disorder in western societies, mostly affecting elderly population. The most prominent symptom includes decrease in cognitive function, which in turn leads to changes in the behavioural patterns of an individual. Both acetylcholinesterase and butyrylcholinesterase still represent the only pharmacotherapy able to affect the increase of the acetylcholine neurotransmitter in the brain[1–3]. Oxidative stress is most commonly associated with the development of many diseases, including neurodegenerative disorders[6]. It was reported that ITCs protect the blood-brain barrier from oxidative stress-induced injury[15]. 11 commercially available ITCs were tested for their cholinesterase inhibitory (using Ellman’s method), and antioxidant (using DPPH, ORAC, Briggs-Rauscher, Rancimat, and FRAP method) activities as well as anti-inflammatory activity via PGE-2 synthesis suppression through COX-2 inhibition
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