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Calcium ionophoretic properties of ferutinin were re-evaluated in solvent-containing bilayer lipid membranes. The slopes of conductance–concentration curves suggest that in the presence of a solvent in the membrane the majority of complexes appear to consist of a single terpenoid molecule bound to one Ca ion. By contrast, the stoichiometry of ferutinin–Ca2+ complexes in acetone determined using the conductometric method was 2 : 1. While the cation–cation selectivity of ferutinin did not change, the cation–anion selectivity slightly decreased in solvent containing membranes. FT-IR and NMR data together with DFT calculations at the B3LYP/6-31G(d) level of theory indicate that in the absence of Ca ions ferutinin molecules are hydrogen-bonded at the phenol hydroxyl groups. The variations of absorption assigned to –OH and –C–O stretching mode suggest that ferutinin interacts strongly with Ca ions via the hydroxyl group of ferutinol and carboxyl oxygen of the complex ether bond. The coordination through the carbonyl group of ferutinin was demonstrated by theoretical calculations. Taken together, ferutinin molecules form H-bonded dimers, while complexation of Ca2+ by ferutinin ruptures this hydrogen bond due to spatial re-orientation of the ferutinin molecules from parallel to antiparallel alignment. [ABSTRACT FROM AUTHOR]

Pomegranate and its by-products contain a broad spectrum of phytochemicals, such as flavonoids, phenolic acids and tannins, having pleiotropic preventive and prophylactic properties in health disorders related to oxidative stress and microbial contamination. Here, we examined the biological effects of a pomegranate peel ellagitannins-enriched (>90%) extract, PETE. In vitro studies revealed that PETE has a strong antiradical action towards synthetic radicals and biologically relevant ROS surpassing or comparable to that of Trolox. In cellular models, it showed concentration-dependent (25-100 µg/mL) yet opposing effects depending on the cell membrane type and exposure conditions. In erythrocytes, PETE protected membrane integrity in the presence of the strong oxidant HClO and restored reduced glutathione levels to up to 85% of the control value while having much weaker acute and long-term intrinsic effects. Such protection persisted even after the removal of the extract from cells, indicating strong membrane interaction. In HeLa cancer cells, and at concentrations lower than those used for red blood cells, PETE induced robust potentiation of ROS production and mitochondrial potential dissipation, leading to autophagy-like membrane morphology changes and cell death. In S. aureus , the growth arrest and bacterial death in the presence of PETE (with MIC = 31.25 µg/mL and MBC = 125 µg/mL, respectively) can be linked to the tripled ROS induction by the extract in the same concentration range. This study indicates a specificity of ROS production by the pomegranate extract depending on the type of cell, the concentration of the extract and the time of incubation. This specificity witnesses a strong potential of the extract components as candidates in antioxidant and pro-oxidant therapy.

The goal of this study is to obtain and characterize the complex of quercetin with glycyrrhizic acid, which is known to serve as a drug delivery system. Quercetin is a flavonoid with a wide range of biological activities, including an antimicrobial effect. However, quercetin instability and low bioavailability that limits its use in medical practice makes it necessary to look for new nanoformulations of it. The formation of the GAQ complex (2:1) was confirmed by using UV and FT-IR spectroscopies. It was found that the GAQ exhibited antimicrobial and antihemolytical activities against S. aureus bacteria and its main virulent factor-α-hemolysin. The IC 50 value for the antihemolytical effect of GAQ was 1.923 ± 0.255 µg/mL. Using a fluorescence method, we also showed that the GAQ bound tightly to the toxin that appears to underlie its antihemolytic activity. In addition, another mechanism of the antihemolytic activity of the GAQ against α-hemolysin was shown, namely, its ability to increase the rigidity of the outer layer of the erythrocyte membrane and thus inhibit the incorporation of α-hemolysin into the target cells, increasing their resistance to the toxin. Both of these effects of GAQ were observed at concentrations below the MIC value for S. aureus growth, indicating the potential of the complex as an antivirulence agent.

Tannins are natural plant origin polyphenols that are promising compounds for pharmacological applications due to their strong and different biological activities, including antibacterial activity. Our previous studies demonstrated that sumac tannin, i.e., 3,6-bis-O-di-O-galloyl-1,2,4-tri-O-galloyl-β-D-glucose (isolated from Rhus typhina L.), possesses strong antibacterial activity against different bacterial strains. One of the crucial factors of the pharmacological activity of tannins is their ability to interact with biomembranes, which may result in the penetration of these compounds into cells or the realization of their activity on the surface. The aim of the current work was to study the interactions of sumac tannin with liposomes as a simple model of the cellular membrane, which is widely used in studies focused on the explanation of the physicochemical nature of molecule-membrane interactions. Additionally, these lipid nanovesicles are very often investigated as nanocarriers for different types of biologically active molecules, such as antibiotics. In the frame of our study, using differential scanning calorimetry, zeta-potential, and fluorescence analysis, we have shown that 3,6-bis-O-di-O-galloyl-1,2,4-tri-O-galloyl-β-D-glucose interacts strongly with liposomes and can be encapsulated inside them. A formulated sumac-liposome hybrid nanocomplex demonstrated much stronger antibacterial activity in comparison with pure tannin. Overall, by using the high affinity of sumac tannin to liposomes, new, functional nanobiomaterials with strong antibacterial activity against Gram-positive strains, such as S. aureus , S. epidermitis, and B. cereus , can be formulated.

In this study, using bilayer lipid membrane technique, we report a novel facet of antihemolytic activity of two tannins (1,2,3,4,5-penta-O-galloyl-β-D-glucose (PGG) and 1,2-di-O-galloyl-4,6-valoneoyl-β-D-glucose (dGVG)), which consists in inhibiting the formation of α-hemolysin channels and blocking the conductivity of already formed channels. These effects were observed at tannin concentrations well below minimal inhibitory concentration values for S. aureus growth. Using spectroscopic methods, we show that these two tannins differing in molecular structure but having the same number of -OH groups and aromatic rings form firm complexes with hemolysin in aqueous solutions, which may underlie the disruption of its subsequent interaction with the membrane, thus preventing hemolysis of erythrocytes. In all experimental settings, PGG was the more active compound compared to dGVG, that indicates the important role of the flexibility of the tannin molecule in interaction with the toxin. In addition, we found that PGG, but not dGVG, was able to block the release of the toxin by bacterial cells. This toxin is a strong pathogenic factor causing a number of diseases and therefore is considered as a virulence target for treatment of S. aureus infection, so the data obtained suggest that PGG and possibly other tannins of similar structure have therapeutic potential in fighting the virulence of S. aureus., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

It is well known that accumulation of advanced glycation ends products (AGEs) lead to various diseases such as diabetes and diabetic complications. In this study we showed that hydrolysable tannin from Sumac (Rhus typhina L.)-3,6-bis-O-di-O-galloyl-1,2,4-tri-O-galloyl-β-D-glucose (C 55 H 40 O 34 ) inhibited generation of glycation markers in bovine serum albumin such as AGEs, dityrosine, N'-formylkynurenine and kynurenine under high glucose treatment. This effect was accompanied by stabilization of the protein structure, as was shown using ATR-FT-IR spectroscopy and fluorescence methods. C 55 H 40 O 34 exhibited also a neuroprotective effect in high glucose-exposed Neuro2A cells suppressing ROS formation and expression of phospho NF-κβ and iNOS. At the same time C 55 H 40 O 34 increased expression of heme oxygenase-1 and NAD(P)H: quinone oxidoreductase and mitochondrial complex I and V activities. Results from this study demonstrates a potent antiglycation activity of C 55 H 40 O 34 in vitro and indicates its possible therapeutic application in glycation related diseases., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Search for novel antimicrobial agents, including plant-derived flavonoids, and evaluation of the mechanisms of their antibacterial activities are pivotal objectives. The goal of this study was to compare the antihemolytic activity of flavonoids, quercetin, naringenin and catechin against sheep erythrocyte lysis induced by α-hemolysin (αHL) produced by the Staphylococcus aureus strain NCTC 5655. We also sought to investigate the membrane-modifying action of the flavonoids. Lipophilic quercetin, but not naringenin or catechin, effectively inhibited the hemolytic activity of αHL at concentrations (IC 50 = 65 ± 5 µM) below minimal inhibitory concentration values for S. aureus growth. Quercetin increased the registered bacterial cell diameter, enhanced the fluidity of the inner and surface regions of bacterial cell membranes and raised the rigidity of the hydrophobic region and the fluidity of the surface region of erythrocyte membranes. Our findings provide evidence that the antibacterial activities of the flavonoids resulted from a disorder in the structural organization of bacterial cell membranes, and the antihemolytic effect of quercetin was related to the effect of the flavonoid on the organization of the erythrocyte membrane, which, in turn, increases the resistance of the target cells (erythrocytes) to αHL and inhibits αHL-induced osmotic hemolysis due to prevention of toxin incorporation into the target membrane. We confirmed that cell membrane disorder could be one of the direct modes of antibacterial action of the flavonoids.

Polyphenols, including tannins, are phytochemicals with pronounced antimicrobial properties. We studied the activity of two hydrolysable tannins, (i) gallotannin-1,2,3,4,5-penta-O-galloyl-β-D-glucose (PGG) and (ii) ellagitannin-1,2-di-O-galloyl-4,6-valoneoyl-β-D-glucose (dGVG), applied alone and in combination with antibiotics against Staphylococcus aureus strain 8324-4. We also evaluated the effect of these tannins on bacterial membrane integrity and fluidity and studied their interaction with membrane proteins and lipids. A correlation between the antimicrobial activity of the tannins and their membranotropic action depending on the tannin molecular structure has been demonstrated. We found that the antibacterial activity of PGG was stronger than dGVG, which can be associated with its larger flexibility, dipole moment, and hydrophobicity. In addition, we also noted the membrane effects of the tannins observed as an increase in the size of released bacterial membrane vesicles.

Phenolic acids represent a class of drugs with mild antibacterial properties. We have synthesized iodinated gallic and ferulic acids and together with commercially available iodinated forms of salicylic acids studied their cytotoxicity, bacteriostatic and anti-virulence action. Out of these, iodogallic acid had lowest minimal inhibitory concentration (MIC) against Staphylococcus aureus (MIC = 0.4 mM/118.8 μg/ml). Yet, it had strong effect on erythrocyte membrane lipid ordering and on α-hemolysin secretion by the bacteria at lower non-bacteriostatic and non-cytotoxic concentrations (<0.1 mM). Iodogallic acid formed static complexes with α-hemolysin in solutions (logK b  = 4.69 ± 0.07) and inhibited its nano-pore conduction in artificial lipid bilayers (IC50 = 37.9 ± 5.3 μM). These effects of iodogallic acid converged on prevention of hemolysis induced by α-hemolysin (IC50 = 41.5 ± 4.2 μM) and pointed to enhanced and diverse anti-virulence properties of some aryl iodides. The analysis of molecular surface electrostatic charge distribution, molecular hydrophilicity, electronegativity, and dipole moment of studied compounds suggested the importance of the number of hydroxyl groups and their proximity to iodine in anti-virulence activity manifestation. In iodogallic acid, charge redistribution resulted in higher hydrophilicity without concomitant change in overall molecular electronegativity and dipole moment compared to non-iodinated gallic acid. This study shows new directions for the development of antibacterial/antivirulence therapeutics., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Tannins belong to plant secondary metabolites exhibiting a wide range of biological activity. One of the important aspects of the realization of the biological effects of tannins is the interaction with lipids of cell membranes. In this work we studied the interaction of two hydrolysable tannins: 1,2,3,4,6-penta-O-galloyl-β-d-glucose (PGG) and 1,2-di-O-galloyl-4,6-valoneoyl-β-d-glucose (T1) which had the same number of both aromatic rings (5) and hydroxyl groups (15) but differing in flexibility due to the presence of valoneoyl group in the T1 molecule with DMPC (dimyristoylphosphatidylcholine) lipid nano-vesicles (liposomes). Tannins-liposomes interactions were investigated using fluorescence spectroscopy, differential scanning calorimetry, laser Doppler velocimetry, dynamic light scattering and Fourier Transform Infra-Red spectroscopy. It was shown that more flexible PGG molecules stronger decreased the microviscosity of the liposomal membranes and increased the values of negative zeta potential in comparison with the more rigid T1. Both compounds diminished the phase transition temperature of DMPC membranes, interacted with liposomes via PO groups of head of phospholipids and their hydrophobic regions. These tannins neutralized DPPH free radicals with the stoichiometry of the reaction equal 1:1. The effects of the studied compounds on liposomes were discussed in relation to tannin quantum chemical parameters calculated by molecular modeling., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Plants have served for centuries as sources of compounds useful for human health such as antioxidant, anti-diabetic and antitumor agents. They are also rich in nutrients that improve the human diet. Growing demands for these compounds make it important to seek new sources for them. Hippophae rhamnoides L. is known as a plant with health-promoting properties. In this study we investigated the chemical composition and biological properties of bioactive components of ethanol extracts from leaves and twigs of H. rhamnoides L. Chemical components such as the total content of phenolic compounds, vitamins and amino acids and the antioxidant activities of these compounds in cellular and cell-free systems were assessed. The results suggest that the studied extracts are rich in bioactive compounds with potent antioxidant properties. Cytotoxicity and hemotoxicity assays showed that the extracts had low toxicity on human cells over the range of concentrations tested. Interaction with human serum albumin was investigated and conformational changes were observed. Our results indicate that leaf and twig extracts of H. rhamnoides L. should be considered as a non-toxic source of bioactive compounds which may be of interest to the food, pharmaceutical and cosmetic industries., (© 2022. The Author(s).)

In the present work, we investigated the interaction of flavonoids (quercetin, naringenin and catechin) with cellular and artificial membranes. The flavonoids considerably inhibited membrane lipid peroxidation in rat erythrocytes treated with tert-butyl hydroperoxide (700 μM), and the IC 50 values for prevention of this process were equal to 9.7 ± 0.8 μM, 8.8 ± 0.7 μM, and 37.8 ± 4.4 μM in the case of quercetin, catechin and naringenin, respectively, and slightly decreased glutathione oxidation. In isolated rat liver mitochondria, quercetin, catechin and naringenin (10-50 μM) dose-dependently increased the sensitivity to Ca 2+ ions - induced mitochondrial permeability transition. Using the probes TMA-DPH and DPH we showed that quercetin rather than catechin and naringenin strongly decreased the microfluidity of the 1,2-dimyristoyl-sn-glycero-3-phosphocholine liposomal membrane bilayer at different depths. On the contrary, using the probe Laurdan we observed that naringenin transfer the bilayer to a more ordered state, whereas quercetin dose-dependently decreased the order of lipid molecule packing and increased hydration in the region of polar head groups. The incorporation of the flavonoids, quercetin and naringenin and not catechin, into the liposomes induced an increase in the zeta potential of the membrane and enlarged the area of the bilayer as well as lowered the temperature and the enthalpy of the membrane phase transition. The effects of the flavonoids were connected with modification of membrane fluidity, packing, stability, electrokinetic properties, size and permeability, prevention of oxidative stress, which depended on the nature of the flavonoid molecule and the nature of the membrane., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Tannins belong to secondary metabolites of plants that exhibit a variety of biological activities, including antiviral one. In this research, we studied the interaction of human serum albumin (HSA) with two ellagitannins: 2,4-valoneoyl-3,6-hexahydroxydiphenoyl-β-d-glucose (T1) and 1,2-di-O-galloyl-3,6-valoneoyl-β-d-glucose (T2) from Euphorbia species having antiviral potential against HIV and differing in molecular flexibility due to the presence of valoneoyl- and hexahydroxydiphenoyl groups. A fluorescence analysis demonstrated that the tannins studied strongly interacted with HSA and quenched tryptophan (Trp) fluorescence in the range of 0.25-4 μM. The quenching occurred by a static mechanism. The logK b for more flexible T2 was generally higher in comparison with stiffer T1 (4.94 ± 0.82 vs. 4.12 ± 0.31 and 4.94 ± 0.53 vs. 4.07 ± 0.45 for 296 K and 303 K respectively). The difference was also in the nature of the forces participating in the interaction with HSA. The stiff T1 reacted with HSA via hydrophobic forces, whereas the flexible T2 interacted with the protein by van der Waals forces and hydrogen bonds. The nature of the bonds was also confirmed by a study of the hydrophobicity of the compounds. Zeta-potential measurements showed slightly modifications of albumin electric charge but without significant changes in the surface structure of protein. Surface Plasmon Resonance imaging (SPRi) revealed that the used tannins fully saturated a 3 ng/mL solution of albumin at the concentrations of above 15 ng/mL. Our experiments clearly showed that the tannins used formed complexes with HSA and that the flexibility of the tannins was an important factor determining their interaction with the protein., Competing Interests: Declaration of Competing Interest Authors declare no ethical, financial or other conflict of interests., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The objective of the study was a comparative analysis of the antihemolytic activity against two Staphylococcus aureus strains (8325-4 and NCTC 5655) as well as α-hemolysin and of the membrane modifying action of four hydrolysable tannins with different molecular mass and flexibility: 3,6-bis-O-di-O-galloyl-1,2,4-tri-O-galloyl-β-D-glucose (T1), 1,2,3,4,5-penta-O-galloyl-β-D-glucose (T2), 3-O-galloyl-1,2-valoneoyl-β-D-glucose (T3) and 1,2-di-O-galloyl-4,6-valoneoyl-β-D-glucose (T4). We showed that all the compounds studied manifested antihemolytic effects in the range of 5-50 µM concentrations. However, the degree of the reduction of hemolysis by the investigated tannins was not uniform. A valoneoyl group-containing compounds (T3 and T4) were less active. Inhibition of the hemolysis induced by α-hemolysin was also noticed on preincubated with the tannins and subsequently washed erythrocytes. In this case the efficiency again depended on the tannin structure and could be represented by the following order: T1 > T2 > T4 > T3. We also found a relationship between the degree of antihemolytic activity of the tannins studied and their capacity to increase the ordering parameter of the erythrocyte membrane outer layer and to change zeta potential. Overall, our study showed a potential of the T1 and T2 tannins as anti-virulence agents. The results of this study using tannins with different combinations of molecular mass and flexibility shed additional light on the role of tannin structure in activity manifestation.

It is well known that the terpenoid ferutinin (4-oxy-6-(4-oxybenzoyloxy) dauc-8,9-en), isolated from the plant Ferula tenuisecta, considerably increases the permeability of artificial and cellular membranes to Ca 2+ -ions and produces apoptotic cell death in different cell lines in a mitochondria-dependent manner. The present study was designed for further evaluation of the mechanism(s) of mitochondrial effects of ferutinin using isolated rat liver mitochondria. Our findings provide evidence for ferutinin at concentrations of 5-27 µM to decrease state 3 respiration and the acceptor control ratio in the case of glutamate/malate as substrates. Ferutinin alone (10-60 µM) also dose-dependently dissipated membrane potential. In the presence of Ca 2+ -ions, ferutinin (10-60 µM) induced considerable depolarization of the inner mitochondrial membrane, which was partially inhibited by EGTA, and permeability transition pore formation, which was diminished partly by cyclosporin A, and did not influence markedly the effect of Ca 2+ on mitochondrial respiration. Ruthenium Red, a specific inhibitor of mitochondrial calcium uniporter, completely inhibited Ca 2+ -induced mitochondria swelling and membrane depolarization, but did not affect markedly the stimulation of these Ca 2+ -dependent processes by ferutinin. We concluded that the mitochondrial effects of ferutinin might be primarily induced by stimulation of mitochondrial membrane Ca 2+ -permeability, but other mechanisms, such as driving of univalent cations, might be involved.

Several studies reported that bisphenol A (BPA) and its metabolite hydroquinone (HQ) have adverse effects on human and animal health. In this work, a comparative study of influence of the BPA and HQ, environment pollutants, on human erythrocytes was carried out. It was shown that BPA and HQ to varying extents caused oxidative damage in human erythrocytes: hemolysis, decreased GSH level, and methemoglobin formation. It was demonstrated that hydrolysable tannins 3,6-bis-O-di-O-galloyl-1,2,4-tri-O-galloyl-β-D-glucose (C 55 H 40 O 34 ) and 1,2,3,4,6-penta-O-galloyl-β-D-glucose (C 41 H 32 O 26 ) (PGG) isolated from the Rhus typhina L. leaves in the range of 1-50 μM concentrations inhibited hemolysis and methemoglobin formation and also increased intracellular reduced glutathione in erythrocytes treated with BPA or HQ. It was revealed by electron paramagnetic resonance (EPR) using 5-doxyl-stearic acid (5-DS) that C 55 H 40 O 34 and C 41 H 32 O 26 increased the rigidity of erythrocyte membranes at the depth of 5th carbon atom of the fatty acid hydrocarbon chain. Taken together, these results allow to conclude that tannins from the Rhus typhina L. leaves protect erythrocytes from oxidative stress caused by BPA or HQ both due to their antioxidant activity as well as their interaction with the erythrocyte membrane components.

The etiology of Parkinson's disease (PD) relates to α-synuclein, a small protein with the ability to aggregate and form Lewy bodies. One of its prevention strategies is inhibition of α-synuclein oligomerization. We have investigated the interaction of α-synuclein and human serum albumin with 3,6-bis-О-di-О-galloyl-1,2,4-tri-О-galloyl-β-d-glucose (a tannin isolated from the plant Rhus typhina). Using fluorescence spectroscopy method we found that this tannin interacts strongly with α-synuclein forming complexes. Circular dichroism analysis showed a time-dependent inhibition of α-synuclein aggregation in the presence of the tannin. On the other hand, 3,6-bis-О-di-О-galloyl-1,2,4-tri-О-galloyl-β-d-glucose had a much stronger interaction with human serum albumin than α-synuclein. The calculated binding constant for tannin-protein interaction was considerably higher for albumin than α-synuclein. This tannin interacted with albumin through a "sphere of action" mechanism. The results lead to the conclusion that 3,6-bis-О-di-О-galloyl-1,2,4-tri-О-galloyl-β-d-glucose is a potent preventive compound against Parkinson's disease. However, this tannin interacts very strongly with human serum albumin, significantly reducing the bioavailability of this compound., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Polyphenols of plant origin with wide range of antiradical activity can prevent diseases caused by oxidative and inflammatory processes. In this study, we show using ESR method that the purified water-soluble extract from leaves of Rhus typhina L. containing hydrolysable tannins and its main component, 3,6-bis-O-di-O-galloyl-1,2,4-tri-O-galloyl-β-D-glucose (C 55 H 40 O 34 ), displayed a strong antiradical activity against the synthetic 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) in homogenous (solution) and heterogeneous systems (suspension of DPPH containing liposomes) in the range of 1-10 μg/ml. The C 55 H 40 O 34 and extract at 1-30 μg/ml also efficiently, but to a various degree, decreased reactive oxygen and nitrogen species (RONS) formation induced in erythrocytes by oxidants, following the sequence: tert-butyl hydroperoxide (tBuOOH) > peroxynitrite (ONOO - ) >hypochlorous acid (HClO). The explanation of these differences should be seen in the specificity of scavenging different RONS types. These relationships can be represented for C 55 H 40 O 34 and the extract by the following order of selectivity: O .- 2  ≥ NO· > ·OH > 1 O 2 . The extract exerted a more pronounced antiradical effect in reaction with DPPH and ROS in all models of oxidative stress in erythrocytes in comparison with C 55 H 40 O 34 . The redox processes between the extract components and their specificity in relation to RONS can underlie this effect.

We have examined the interaction between hydrolysable tannin 1-O-galloyl-4,6-hexahydroxydiphenoyl-β-D-glucose (OGβDG) with neutral liposomes as a model of cell membranes composed of three lipids: lecithin, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) at different mass ratios. OGβDG in the concentration range 0.5-15 µg/ml (0.4-12 µM) strongly interacts with liposomal membranes by changing their structure, surface charge and fluidity. Used OGβDG molecules decrease and increase the rigidity of hydrophilic surface and hydrophobic parts of liposomes, respectively. At higher concentrations of tannin (>15 µM), liposomes are aggregated. Fourier Transform Infra-Red (FTIR) analysis showed that mainly -OH groups from OGβDG and also PO(2-) groups from phospholipids are responsible for the interaction. Obtained data indicate the importance of membrane lipid composition in interactions between tannins and cells.

The present study was undertaken for further elucidation of the mechanisms of flavonoid biological activity, focusing on the antioxidative and protective effects of cranberry flavonoids in free radical-generating systems and those on mitochondrial ultrastructure during carbon tetrachloride-induced rat intoxication. Treatment of rats with cranberry flavonoids (7 mg/kg) during chronic carbon tetrachloride-induced intoxication led to prevention of mitochondrial damage, including fragmentation, rupture and local loss of the outer mitochondrial membrane. In radical-generating systems, cranberry flavonoids effectively scavenged nitric oxide (IC50  = 4.4 ± 0.4 µg/ml), superoxide anion radicals (IC50  = 2.8 ± 0.3 µg/ml) and hydroxyl radicals (IC50  = 53 ± 4 µg/ml). The IC50 for reduction of 1,1-diphenyl-2-picrylhydrazyl radicals (DPPH) was 2.2 ± 0.3 µg/ml. Flavonoids prevented to some extent lipid peroxidation in liposomal membranes and glutathione oxidation in erythrocytes treated with UV irradiation or organic hydroperoxides as well as decreased the rigidity of the outer leaflet of the liposomal membranes. The hepatoprotective potential of cranberry flavonoids could be due to specific prevention of rat liver mitochondrial damage. The mitochondria-addressed effects of flavonoids might be related both to radical-scavenging properties and modulation of various mitochondrial events., (Copyright © 2015 John Wiley & Sons, Ltd.)

Tannins, secondary plant metabolites, possess diverse biological activities and can interact with biopolymers such as lipids or proteins. Interactions between tannins and proteins depend on the structures of both and can result in changes in protein structure and activity. Because human serum albumin is the most abundant protein in plasma and responsible for interactions with important biological compounds (e.g. bilirubin) and proper blood pressure, therefore, it is very important to investigate reactions between HSA and tannins. This paper describes the interaction between human serum albumin (HSA) and two tannins: bihexahydroxydiphenoyl-trigalloylglucose (BDTG) and 1-O-galloyl-4,6-hexahydroxydiphenoyl-β-d-glucose (OGβDG), isolated from Geranium sanguineum and Oenothera gigas leafs, respectively. Optical (spectrofluorimetric) and chiral optical (circular dichroism) methods were used in this study. Fluorescence analysis demonstrated that OGβDG quenched HSA fluorescence more strongly than BDTG. Both OGβDG and BDTG formed complexes with albumin and caused a red shift of the fluorescence spectra but did not significantly change the protein secondary structure. Our studies clearly demonstrate that the tested tannins interact very strongly with human serum albumin (quenching constant K=88,277.26±407.04 M(-1) and K=55,552.67±583.07 M(-1) respectively for OGβDG and BDTG) in a manner depending on their chemical structure., (Copyright © 2014 Elsevier B.V. All rights reserved.)

In this study, we found that the sumac tannins (Rhus typhina L.) exert to a various extent antihemolytic effects and antibacterial activity against Bacillus cereus and Pseudomonas aeruginosa depending on structural specificity of bacteria and different mechanisms of their toxic action. The sumac tannins exert the most expressed activity against B. cereus. The antihemolytic effect of the sumac tannins seems to be connected to a greater extent with their modifying action on the erythrocyte membrane structure. It was found that the sumac tannins are incorporated into the erythrocyte membrane, causing transformation of discocytes into echinocytes and enhancing the rigidity of the hydrophilic region of the lipid bilayer. We suggest that the embedding of sumac tannins into the membrane of erythrocytes alters their physical properties and, as a consequence, can limit their interaction with bacterial toxins.

Background: Silibinin, a naturally-occurring flavonoid produced by milk thistle, possesses antioxidant, anti-inflammatory and cancer-preventive activities. In the current study, we examined the effects of silibinin on the expression of secreted phospholipase A2 (sPLA2) enzymes, especially those of group IIA (hGIIA), which play a crucial role in inflammation and carcinogenesis., Materials and Methods: The effects of silibinin on sPLA2 expressions in human HepG2 hepatoma and PC-3 prostate cancer cells were analyzed using quantitative reverse transcription-polymerase chain reaction and enzyme linked immunosorbent assay technique., Results: Silibinin inhibited the expression of hGIIA in unstimulated and cytokine-primed HepG2 and PC-3 cells. The mRNA levels of sPLA2 of groups IB, III and V were also significantly decreased by silibinin. Analyses of transcription factor activation suggest that nuclear factor-κB, but not specificity protein 1 (SP1) is implicated in the silibinin-mediated down-regulation of hGIIA., Conclusion: Silibinin exhibits inhibitory effects on basal and cytokine-induced expression of sPLA2s in cancer cells and therefore, may have the potential to protect against up-regulation of hGIIA and other sPLA2 isoforms during inflammation and cancer.

Previously we have shown a toxic effect of the organometallic compound triphenyllead (TPhPb) on cells. In the present study we evaluated the destructive effect of TPhPb on model systems--serum albumin and liposome membranes--alone and under UVB irradiation. UVB irradiation of bovine serum albumin results in protein S-S bond reduction, free SH- and CO- group formation and decrease in fluorescence intensity of tryptophans. Triphenyllead chloride alone and under UVB irradiation did not induce protein oxidation, measured as formation of carbonyl groups, in serum albumin; however, it decreased the content of SH- groups in both cases (alone and under UVB radiation) in a dose-dependent manner. It was found that triphenyllead chloride alone did not induce lipid peroxidation of liposomes but increased their fluidity. However, under UVB irradiation TPhPb dramatically enhances the pro-oxidant action of UVB in a manner dependent on concentration and intensity of radiation, and these effects were suppressed by Trolox. These results suggest that the toxicity of TPhPb under UVB irradiation is due to formation of radical forms of the compound and its disordered effects on the membrane structure., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The objective of this study is analysis of stability and antioxidant and antiradical activities of the gossypol derivative - megosin conjugated with N-polyvinylpyrrolidone (PVP). The results of study have shown the greater stability of megosin+PVP than megosin in aqueous solution of wide range of pH. Here we also demonstrated that megosin+PVP, named rometin, possess high antioxidant activity in the same range as well known antioxidant trolox as determined by its ability to scavenge free ABTS(+) and DPPH radicals in vitro. In addition, megosin+PVP was able to prevent accumulation of products of lipid peroxidation (thiobarbituric acid reactive substances and diene conjugates) and lysophospholipids formation in mitochondria membranes caused by CCl(4)-induced oxidative stress in rat liver in vivo. Furthermore, megosin+PVP rescued mitochondrial functions, such as respiration and oxidative phosphorylation, which declined after CCl(4) administration. Thus we present that the conjugation of megosin to PVP increase its stability and remain antioxidant activity in vivo and in vitro., (Copyright © 2012 Elsevier B.V. All rights reserved.)