Alkaloids from Berberis vulgaris and their biological activity connected to Alzheimer's disease

Alzheimer's disease (AD) is neurodegenerative disease with specific neuropathological changes, which are observed at molecular level. Nevertheless, ethiopathogenesis is still not clear and therapy is only symptomatic.

Berberine, an isoquinoline alkaloid from Berberis sp. is known agent, which interferes with many processes present within the course of the disease. The aim of this phytochemical study was to isolate tertiary alkaloids with potential neuroprotective activity, which could have less cytotoxic effect and better bioavailability.

The primary extract was acquired from dried barberry root bark by extraction with ethanol and then was subjected to liquid/liquid extraction with different pH and treated by standard chromatographic methods. Alkaloid structures were determined by spectroscopic methods (MS, NMR). Isolated alkaloids were subsequently tested in vitro for their inhibition activity in term of human acetylcholinesterase (AChE), butyrylcholinesterase (BuChE) and prolyl oligopeptidase (POP); IC₅₀ values were determined. The most active alkaloids were tested for type of cholinesterase inhibition and ability to cross blood brain barrier (BBB).

Some of the alkaloids were weak AChE inhibitors: the berlambine, bersavine, obamegine and berbostrejdine (IC₅₀ ranged from 55.3 to 97.4 µM). The last one inhibited also BuChE (IC₅₀ 6.9 ± 1,0 µM). The most potent inhibitor of BuChE was aromoline with IC₅₀ value of 0.82 ± 0.1 µM. The type of inhibition of aromoline was determined at horse plasma BuChE model, it acted via a mixed mechanism in a dose-dependent manner. Based on parallel artificial permeation assay it is not able to cross BBB by passive permeation.

The promising inhibition activity against POP was shown by bersavine (with IC₅₀ of 67.3 ± 6.2 µM), inhibition potency of aromoline and berlambine was comparable to the standard berberine (IC₅₀= 142.3 ± 21.1 µM).