Cannabis Sativa L. Flower and Bud Extracts Inhibited In vitro Cholinesterases and β-Secretase Enzymes Activities: Possible Mechanisms of Cannabis Use in Alzheimer Disease

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Abstract

Background: There are anecdotal claims on the use of Cannabis sativa L. in the treatment of Alzheimer’s disease, but there is a lack of scientific data to support the efficacy and safety of Cannabis sativa L. for Alzheimer’s disease.

Aim: The aim of the study was to evaluate the effect of aerial parts of Cannabis sativa L. on the cholinesterases and β-secretase enzymes activities as one of the possible mechanisms of Alzheimer’s disease.

Methods: The phytochemical and heavy metal contents were analysed. The extracts were screened for acetylcholinesterase, butyrylcholinesterase and β-secretase activity. Cytotoxicity of extracts was performed in normal vero and pre-adipocytes cell lines. The extracts were characterized using high-performance thin layer chromatography and high-performance liquid chromatography for their chemical fingerprints. Alkaloids, flavonoids and glycosides were present amongst the tested phytochemicals. Cannabidiol concentrations were comparatively high in the hexane and dichloromethane than in dichloromethane: methanol (1:1) and methanol extracts.

Results: Hexane and dichloromethane extracts showed a better inhibitory potential towards cholinesterase activity, while water, hexane, dichloromethane: methanol (1:1) and methanol showed an inhibitory potential towards β-secretase enzyme activity. All extracts showed no cytotoxic effect on pre-adipocytes and vero cells after 24- and 48-hours of exposure.

Conclusion: Therefore, this may explain the mechanism through which AD symptoms may be treated and managed by Cannabis sativa L. extracts.

Keywords: Cannabis sativa L., HPTLC, Cholinesterase inhibition, β-secretase inhibition, cytotoxicity, Alzheimer’s Disease.

Graphical Abstract