Papers by Katerina Macakova
2,3-Dehydrosilybin (DHS) was previously shown to chelate and reduce both copper and iron ions. In... more 2,3-Dehydrosilybin (DHS) was previously shown to chelate and reduce both copper and iron ions. In this study, similar experiments with 2,3-dehydrosilychristin (DHSCH) showed that this congener of DHS also chelates and reduces both metals. Statistical analysis pointed to some differences between both compounds: in general, DHS appeared to be a more potent iron and copper chelator, and a copper reducing agent under acidic conditions, while DHSCH was a more potent copper reducing agent under neutral conditions. In the next step, both DHS and DHSCH were tested for metal-based Fenton chemistry in vitro using HPLC with coulometric detection. Neither of these compounds were able to block the iron-based Fenton reaction and, in addition, they mostly intensified hydroxyl radical production. In the copper-based Fenton reaction, the effect of DHSCH was again prooxidant or neutral, while the effect of DHS was profoundly condition-dependent. DHS was even able to attenuate the reaction under some ...
Nutrients
Vitamin A is a group of vital micronutrients widely present in the human diet. Animal-based produ... more Vitamin A is a group of vital micronutrients widely present in the human diet. Animal-based products are a rich source of the retinyl ester form of the vitamin, while vegetables and fruits contain carotenoids, most of which are provitamin A. Vitamin A plays a key role in the correct functioning of multiple physiological functions. The human organism can metabolize natural forms of vitamin A and provitamin A into biologically active forms (retinol, retinal, retinoic acid), which interact with multiple molecular targets, including nuclear receptors, opsin in the retina and, according to the latest research, also some enzymes. In this review, we aim to provide a complex view on the present knowledge about vitamin A ranging from its sources through its physiological functions to consequences of its deficiency and metabolic fate up to possible pharmacological administration and potential toxicity. Current analytical methods used for its detection in real samples are included as well.
Molecules, Apr 5, 2019
In recent studies, several alkaloids acting as cholinesterase inhibitors were isolated from Coryd... more In recent studies, several alkaloids acting as cholinesterase inhibitors were isolated from Corydalis cava (Papaveraceae). Inhibitory activities of (+)-thalictricavine (1) and (+)-canadine (2) on human acetylcholinesterase (hAChE) and butyrylcholinesterase (hBChE) were evaluated with the Ellman's spectrophotometric method. Molecular modeling was used to inspect the binding mode of compounds into the active site pocket of hAChE. The possible permeability of 1 and 2 through the blood-brain barrier (BBB) was predicted by the parallel artificial permeation assay (PAMPA) and logBB calculation. In vitro, 1 and 2 were found to be selective hAChE inhibitors with IC 50 values of 0.38 ± 0.05 µM and 0.70 ± 0.07 µM, respectively, but against hBChE were considered inactive (IC 50 values > 100 µM). Furthermore, both alkaloids demonstrated a competitive-type pattern of hAChE inhibition and bind, most probably, in the same AChE sub-site as its substrate. In silico docking experiments allowed us to confirm their binding poses into the active center of hAChE. Based on the PAMPA and logBB calculation, 2 is potentially centrally active, but for 1 BBB crossing is limited. In conclusion, 1 and 2 appear as potential lead compounds for the treatment of Alzheimer's disease.
Nutrients
Vitamin C (L-ascorbic acid) has been known as an antioxidant for most people. However, its physio... more Vitamin C (L-ascorbic acid) has been known as an antioxidant for most people. However, its physiological role is much larger and encompasses very different processes ranging from facilitation of iron absorption through involvement in hormones and carnitine synthesis for important roles in epigenetic processes. Contrarily, high doses act as a pro-oxidant than an anti-oxidant. This may also be the reason why plasma levels are meticulously regulated on the level of absorption and excretion in the kidney. Interestingly, most cells contain vitamin C in millimolar concentrations, which is much higher than its plasma concentrations, and compared to other vitamins. The role of vitamin C is well demonstrated by miscellaneous symptoms of its absence—scurvy. The only clinically well-documented indication for vitamin C is scurvy. The effects of vitamin C administration on cancer, cardiovascular diseases, and infections are rather minor or even debatable in the general population. Vitamin C is r...
Nutrients
Silymarin is a traditional drug and food supplement employed for numerous liver disorders. The av... more Silymarin is a traditional drug and food supplement employed for numerous liver disorders. The available studies indicate that its activities may be broader, in particular due to claimed benefits in some cardiovascular diseases, but the contributions of individual silymarin components are unclear. Therefore, we tested silymarin flavonolignans as pure diastereomers as well as their sulfated metabolites for potential vasorelaxant and antiplatelet effects in isolated rat aorta and in human blood, respectively. Eleven compounds from a panel of 17 tested exhibited a vasorelaxant effect, with half maximal effective concentrations (EC50) ranging from 20 to 100 µM, and some substances retained certain activity even in the range of hundreds of nM. Stereomers A were generally more potent as vasorelaxants than stereomers B. Interestingly, the most active compound was a metabolite—silychristin-19-O-sulfate. Although initial experiments showed that silybin, 2,3-dehydrosilybin, and 2,3-dehydrosil...
Natural Product Communications, Nov 1, 2010
The roots and aerial parts of Eschscholzia californica Cham. (Papaveraceae) were extracted with e... more The roots and aerial parts of Eschscholzia californica Cham. (Papaveraceae) were extracted with ethanol. Repeated column chromatography, preparative TLC, and crystallization led to the isolation of fourteen isoquinoline alkaloids, the structures of which were determined on the basis of spectroscopic techniques and by comparison with literature values. One of the compounds isolated, 1-(3-hydroxy-4-methoxybenzyl)-2-methyl-6,7-methylenedioxy-1,2,3,4-tetrahydroisoquinoline (14), has not previously been isolated from a natural source. All isolated compounds were tested for human blood acetylcholinesterase (HuAChE) and human plasma butyrylcholinesterase (HuBuChE) inhibition activity. None of the compounds isolated significantly inhibited both HuAChE and HuBuChE, but the two benzylisoquinoline alkaloids, reticuline 9 and 14, showed promising inhibitory activity against HuBuChE.
Pharmaceutical Biology, 2016
Context Some mushrooms of the order Polyporales are known for their immunomodulatory actions. Obj... more Context Some mushrooms of the order Polyporales are known for their immunomodulatory actions. Objective The objective of this study is to evaluate the in vitro phagocytic and cytotoxic effects of extracts from polyporales native to Central Europe. Materials and methods The effects of ethanol extracts from 27 polypore species on opsonized zymosaninduced phagocytosis of isolated human neutrophils were tested by a chemiluminescence method. Colon epithelial cell lines, Caco-2 and HT-29, were used for cytotoxicity assays, and extracts were chemically characterized in terms of total phenolic and b-glucan content. Results We observed phagocytosis or respiratory burst enhancing activity in 17 extracts, of which five species, namely Aurantiporus fissilis (Berk. & M.A. Curtis) H. Jahn ex Ryvarden, Trametes gibbosa (Pers.) Fr., Piptoporus betulinus (Bull.) P. Karst, Neolentinus lepideus (Fr.) Redhead & Ginns, Polyporus squamosus (Huds.) Fr., significantly increased phagocytosis in granulocytes by 205, 181, 158, 155 and 141%, respectively. The b-glucan content of the three most potent extracts was 58, 42 and 74 mg/g, respectively, and the polyphenol content was 155.6, 133.5 and 155.2 lmol of gallic acid equivalent/g, respectively. Some extracts showed cytotoxic activity, with higher cytotoxicity in Caco-2 than in HT-29 cells. Pycnoporus cinnabarinus (Jacq.) P. Karst. extract was cytotoxic to both cell lines, with IC 50 values of 81 and 31 lg/mL, respectively. Discussion and conclusion The most promising extracts were from N. lepideus and Polyporus squamosus, which are edible species and may be considered safe. Our findings support their use as culinary preparations or food supplements for various immunological gut disorders.
Oxidative Medicine and Cellular Longevity, 2015
Isoflavones are commonly consumed in many Asian countries and have potentially positive effects o... more Isoflavones are commonly consumed in many Asian countries and have potentially positive effects on human being. Only a few and rather controversial data on their interactions with copper and iron are available to date. 13 structurally related isoflavones were tested in the competitive manner for their Cu/Fe-chelating/reducing properties. Notwithstanding the 5-hydroxy-4-keto chelation site was associated with ferric, ferrous, and cupric chelation, the chelation potential of isoflavones was low and no cuprous chelation was observed. None of isoflavones was able to substantially reduce ferric ions, but the vast majority reduced cupric ions. The most important feature for cupric reduction was the presence of an unsubstituted 4′-hydroxyl; contrarily the presence of a free 5-hydroxyl decreased or abolished the reduction due to chelation of cupric ions. The results from this study may enable additional experiments which might clarify the effects of isoflavones on human being and/or mechani...
Oxidative Medicine and Cellular Longevity, 2015
Isoflavones are commonly consumed in many Asian countries and have potentially positive effects o... more Isoflavones are commonly consumed in many Asian countries and have potentially positive effects on human being. Only a few and rather controversial data on their interactions with copper and iron are available to date. 13 structurally related isoflavones were tested in the competitive manner for their Cu/Fe-chelating/reducing properties. Notwithstanding the 5-hydroxy-4-keto chelation site was associated with ferric, ferrous, and cupric chelation, the chelation potential of isoflavones was low and no cuprous chelation was observed. None of isoflavones was able to substantially reduce ferric ions, but the vast majority reduced cupric ions. The most important feature for cupric reduction was the presence of an unsubstituted 4′-hydroxyl; contrarily the presence of a free 5-hydroxyl decreased or abolished the reduction due to chelation of cupric ions. The results from this study may enable additional experiments which might clarify the effects of isoflavones on human being and/or mechani...
Oxidative Medicine and Cellular Longevity, 2015
Isoflavones are commonly consumed in many Asian countries and have potentially positive effects o... more Isoflavones are commonly consumed in many Asian countries and have potentially positive effects on human being. Only a few and rather controversial data on their interactions with copper and iron are available to date. 13 structurally related isoflavones were tested in the competitive manner for their Cu/Fe-chelating/reducing properties. Notwithstanding the 5-hydroxy-4-keto chelation site was associated with ferric, ferrous, and cupric chelation, the chelation potential of isoflavones was low and no cuprous chelation was observed. None of isoflavones was able to substantially reduce ferric ions, but the vast majority reduced cupric ions. The most important feature for cupric reduction was the presence of an unsubstituted 4′-hydroxyl; contrarily the presence of a free 5-hydroxyl decreased or abolished the reduction due to chelation of cupric ions. The results from this study may enable additional experiments which might clarify the effects of isoflavones on human being and/or mechani...
Chemistry & biodiversity, 2016
Two new isoquinoline alkaloids, named fumaranine (2) and fumarostrejdine (10), along with 18 know... more Two new isoquinoline alkaloids, named fumaranine (2) and fumarostrejdine (10), along with 18 known alkaloids were isolated from aerial parts of Fumaria officinalis. The structures of the isolated compounds were elucidated on the basis of spectroscopic analyses and by comparison with literature data. The absolute configuration of the new compound 2 was determined by comparing its circular dichroism spectra with those of known analogs. Compounds isolated in sufficient amounts were evaluated for their acetylcholinesterase, butyrylcholinesterase, prolyl oligopeptidase (POP), and glycogen synthase kinase-3β inhibitory activities. Parfumidine (8) and sinactine (15) exhibited potent POP inhibition activities (IC50 99±5 and 53±2 μM, resp.).
Natural Product Communications, Jun 1, 2010
The ethanol extracts of 47 mushroom species from the order Boletales were tested for their free r... more The ethanol extracts of 47 mushroom species from the order Boletales were tested for their free radical scavenging activities by means of the DPPH free-radical scavenging and hydrogen peroxide-induced luminol chemiluminescence assays. In the DPPH radical scavenging test, 26 species gave EC50 values of less than 1 mg/mL. The highest activity was exhibited by Gyrodon lividus (0.05 mg/mL). However, in the hydrogen peroxide-induced luminol chemiluminescence assay, only 4 species had EC50 values of less than 1 mg/mL, with the highest activity being exhibited by Strobilomyces floccopus (0.26 mg/mL). When compared with known antioxidants, all the mushroom extracts exhibited relatively low activity in both assays. The free radical scavenging results appeared to be correlated with the total phenol contents of the extracts.
Natural Product Communications, Sep 1, 2011
Alzheimer's disease (AD), characterized by the death of nerve cells in th... more Alzheimer's disease (AD), characterized by the death of nerve cells in the cerebral cortex, is the most common subtype of dementia. Despite the exponential growth in the number of AD patients, acetylcholinesterase (AChE) inhibitors are currently used to treat AD. Plants of the Amaryllidaceae family are known to synthesize a particular type of bioactive compounds, named Amaryllidaceae alkaloids, which have shown AChE inhibitory activity. Alkaloid extracts of three species of Amaryllidaceae were studied with respect to their acetylcholinesterase and butyrylcholinesterase inhibitory activity and alkaloid patterns. Eleven alkaloids were identified by GC/MS. Significant cholinesterase inhibitory activity was demonstrated by the alkaloid extract of N. undulata (IC50,(HuAChE) = 14.3 +/- 1.2 microg/mL; IC50,(HuBuChE) = 33.9 +/- 1.9 microg/mL).
Natural product communications, 2011
Alzheimer's disease (AD), characterized by the death of nerve cells in the cerebral cortex, i... more Alzheimer's disease (AD), characterized by the death of nerve cells in the cerebral cortex, is the most common subtype of dementia. Despite the exponential growth in the number of AD patients, acetylcholinesterase (AChE) inhibitors are currently used to treat AD. Plants of the Amaryllidaceae family are known to synthesize a particular type of bioactive compounds, named Amaryllidaceae alkaloids, which have shown AChE inhibitory activity. Alkaloid extracts of three species of Amaryllidaceae were studied with respect to their acetylcholinesterase and butyrylcholinesterase inhibitory activity and alkaloid patterns. Eleven alkaloids were identified by GC/MS. Significant cholinesterase inhibitory activity was demonstrated by the alkaloid extract of N. undulata (IC50,(HuAChE) = 14.3 +/- 1.2 microg/mL; IC50,(HuBuChE) = 33.9 +/- 1.9 microg/mL).
Fitoterapia, Jan 8, 2015
Prolyl oligopeptidase is a cytosolic serine peptidase that hydrolyses proline-containing peptides... more Prolyl oligopeptidase is a cytosolic serine peptidase that hydrolyses proline-containing peptides at the carboxy terminus of proline residues. It has been associated with schizophrenia, bipolar affective disorder, and related neuropsychiatric disorders and therefore may have important clinical implications. Thirty-one isoquinoline alkaloids of various structural types, previously isolated in our laboratory, were screened for their ability to inhibit prolyl oligopeptidase. Promising results have been showed by alkaloids californidine (IC50 = 55.6 ± 3.5 μM), dihydrosanquinarine (IC50 = 99.1 ± 7.6 μM), corypalmine (IC50 = 128.0 ± 10.5 μM) and N-methyllaurotetanine (IC50 = 135.0 ± 11.7 μM).
Natural product communications, 2012
A new benzyldihydroisoquinoline alkaloid (1) was isolated from the tubers of Corydalis cava and n... more A new benzyldihydroisoquinoline alkaloid (1) was isolated from the tubers of Corydalis cava and named corylucinine. Additionally, 8-trichloromethyl-7,8-dihydropalmatine (2), an isolation artifact of tetrahydropalmatine, was obtained. The structures were established by spectroscopic (including 2D NMR and optical rotation) and HR-ESI-MS methods. Both compounds were tested for human blood acetylcholinesterase (HuAChE) and human plasma butyrylcholinesterase (HuBuChE) inhibitory activity. In comparison with the used standards, both compounds showed only moderate inhibitory activity against HuAChE (IC50,. HuAChE = 127.6 +/- 5.2 microM for 1, and IC50, HuAChE = 82.9 +/- 3.9 microM for 2) and none against HuBuChE.
Natural product communications, 2012
Alkaloid extracts of four Amaryllidaceae species were studied with respect to their acetylcholine... more Alkaloid extracts of four Amaryllidaceae species were studied with respect to their acetylcholinesterase and butyrylcholinesterase inhibitory activity and alkaloid patterns. Twenty-one alkaloids were determined by GC/MS, and seventeen of them identified from their mass spectra and retention times. The GC/MS analysis of the alkaloid extract of Nerine filamentosa is the first phytochemical investigation of this species. Promising erythrocytic acetylcholinesterase inhibitory activity was demonstrated by the alkaloid extracts of Narcissus poeticus var recurvus, Nerine filifolia and N. filamentosa (IC(50,HuAChE) = 6.0 +/- 0.1 microg/mL; IC(50,HuAChE) = 18.5 +/- 0.8 microg/mL, IC(50,HuAChE) = 21.6 +/- 1.1 microg/mL). The most potent inhibitory activity against serum butyrylcholinesterase was shown by extracts of Sternbergia lutea and Nerinefilamentosa (IC(50,HuBuChE) = 3.7 +/- 0.1 microg/mL; IC(50.HuBuChE) = 13.0 +/- 0.7 microg/mL).
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Papers by Katerina Macakova