Isoquinoline Alkaloids from Berberis vulgaris as Potential Lead Compounds for the Treatment of Alzheimer’s Disease

Abstract

Three new alkaloids, bersavine (3), muraricine (4), and berbostrejdine (8), together with seven known isoquinoline alkaloids (1–2, 5–7, 9, and 10) were isolated from an alkaloidal extract of the root bark of Berberis vulgaris. The structures of the isolated compounds were determined by spectroscopic methods, including 1D and 2D NMR techniques, HRMS, and optical rotation, and by comparison of the obtained data with those in the literature. The NMR data of berbamine (5), aromoline (6), and obamegine (7) were completely assigned employing 2D NMR experiments. Alkaloids isolated in sufficient amounts were evaluated for their in vitro acetylcholinesterase, butyrylcholinesterase (BuChE), prolyl oligopeptidase, and glycogen synthase kinase-3β inhibitory activities. Selected compounds were studied for their ability to permeate through the blood–brain barrier. Significant human BuChE (hBuChE) inhibitory activity was demonstrated by 6 (IC50 = 0.82 ± 0.10 μM). The in vitro data were further supported by computational analysis that showed the accommodation of 6 in the active site of hBuChE.

Bersavine: A Novel Bisbenzylisoquinoline Alkaloid with Cytotoxic, Antiproliferative and Apoptosis-Inducing Effects on Human Leukemic Cells

“…Bersavine and berbamine were isolated from an alkaloidal extract of the root bark of Berberis vulgaris (Berberidaceae). The detailed isolation and identification of the structures (1D-, 2D-NMR, HRMS and optical rotation) of the alkaloid has been published by Hostalkova and colleagues [5]. For the experiments, the stock solutions were diluted using the complete culture medium to create final concentrations of 1-50 µM, making sure the concentration of DMSO was <0.1% to avoid any toxic effects on the cells.…”

“…They are biosynthetically obtained from benzyltetrahydroisoquinoline units through phenolic oxidative coupling [4]. The representative of this structural type is alkaloid berbamine from Berberis vulgaris [5]. Since berbamine showed exquisite potency against cancer cell lines, there is a dire need to investigate and bring to light the evidence for possible anticancer activity of hitherto unexplored novel bisbenzylisoquinoline alkaloid bersavine ( Figure 1).…”

“…Since berbamine showed exquisite potency against cancer cell lines, there is a dire need to investigate and bring to light the evidence for possible anticancer activity of hitherto unexplored novel bisbenzylisoquinoline alkaloid bersavine (Figure 1). Bersavine, a natural bisbenzylisoquinoline alkaloid, has been recently isolated for the first time from the root bark Berberis vulgaris L. (Berberidaceae) [5]. Bersavine, in structural analogy with berbamine, incorporates two tetrahydrobenzylisoquinoline moieties combined through two ether linkages.…”

“…In this study, we aimed to elucidate the antiproliferative and cytotoxic activity of bersavine in mini panels with cancer cells. To comprehensively reveal the anticancer potential of bersavine, the evidence for an apoptosis-mediated Bersavine, a natural bisbenzylisoquinoline alkaloid, has been recently isolated for the first time from the root bark Berberis vulgaris L. (Berberidaceae) [5]. Bersavine, in structural analogy with berbamine, incorporates two tetrahydrobenzylisoquinoline moieties combined through two ether linkages.…”

“…Hošt'álková et al described the neuroprotective activity of bersavine, including the capability to inhibit human erythrocyte acetylcholinesterase (hAChE), human serum butyrylcholinesterase (hBuChE) and prolyl oligopeptidase (POP; E.C. 3.4.21.26) activities [5]. However, as far as we know, no evidence supporting the antiproliferative, cytotoxic and proapoptotic activity of bersavine has yet been described.…”