Tannins, novel inhibitors of the volume regulation and the volume-sensitive anion channel

Tsiferova, Nargiza A.; Khamidova, Ozoda J.; Amonov, Anvar; Rakhimova, M. B.; Rustamova, S. I.; Kurbannazaova, R. Sh.; Merzlyak, Petr G.; Abdulladjanova, Nodira; Sabirov, Ravshan Z.

doi:10.2478/afpuc-2019-0016

Cited by 4 publications

(4 citation statements)

References 47 publications

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“…Consistent with this hypothesis, the β-GA, but not the α-GA was previously found to be able to suppress the VSOR-mediated release of glutamate and taurine from primary cultured astrocytes (24). Based on this hypothesis, we may assume that recently identified VSOR-inhibitors of plant origin, such as flavonoids (41) and tannins (42), could also be able to modulate the osmoresistivity of the RBC. In addition, GL and its derivatives are expected to have an impact on the cell death induction and protection in other cell types, in which VSOR plays a critical role (43)(44)(45)(46)(47).…”

Section: Discussionsupporting

confidence: 56%

Effect of glycyrrhizin and its derivatives on integrity of human red blood cells

Fayziev

Merzlyak

Rustamova

et al. 2022

J Herbmed Pharmacol

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Introduction: The first and most prevailing cells that glycyrrhizin (GL) and glycyrrhetinic acid (GA) encounter are red blood cells (RBCs). However, what follows this event is poorly understood. This study aims to evaluate the effect of GL and its derivatives on the integrity of human RBCs. Methods: The integrity of human RBC was assessed under normal isotonic conditions and following osmotic and nystatin-induced colloid-osmotic stress by measuring the amount of hemoglobin released. The pore size was determined by the osmotic protection method. Results: GL was found to be virtually non-hemolytic. However, removal of the carbohydrate moiety of GL imparted significant RBC lytic activity to the cis-(beta-) but not to the trans-(alpha-) isoform of GA. The hemisuccinate radical at position C3 (carbenoxolone) greatly diminished the hemolytic property of GA. The RBC lysis occurred by colloid-osmotic mechanism due to the formation of hydrophilic pores with the radius of ~2.3 nm. At the sublytic doses, the two stereo-isoforms displayed opposite effects on the osmo-resistivity of human RBC: osmoprotection for alpha-GA and osmotic sensibilization for beta-GA. Similar osmotic sensibilization was also observed for GL and carbenoxolone. The two stereo-isoforms exhibited different but not opposite weakening effects on the resistivity of the RBC to the colloid-osmotic stress induced by nystatin, a pore-former. The weakening effect was found intermediate for GL and absent for carbenoxolone. Conclusion: Upon intestinal digestion and absorption, depending on the structure and dosage, the GL hydrolysis products interact with RBC with both beneficial and detrimental consequences.

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Section: Discussionsupporting

confidence: 56%

Effect of glycyrrhizin and its derivatives on integrity of human red blood cells

Fayziev

Merzlyak

Rustamova

et al. 2022

J Herbmed Pharmacol

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“…Other known conventional Cl – channel blockers were also shown to suppress ischemia/reperfusion-induced apoptotic cell death in cardiomyocytes ( Wang et al, 2005 ) and excitotoxic necrotic cell death in cortical neurons and brain slices ( Inoue and Okada, 2007 ) by inhibiting VSOR/VRAC activity. Inhibitory effects of the plant flavonoids ( Xue et al, 2018 ; Rustamova et al, 2019 ), tannins ( Tsiferova et al, 2019 ) and polyphenol gossypol ( Chorieva et al, 2021 ) may provide a clue to discover new, effective and safe modulators targeting VSOR/VRAC. Some conventional Cl – channel blockers were also found to diminish acidotoxic necrotic cell death in HeLa cells ( Wang et al, 2007 ) and cortical neurons ( Sato-Numata et al, 2014 ) by inhibiting ASOR/PAC activity.…”

Section: Perspectivementioning

confidence: 99%

Properties, Structures, and Physiological Roles of Three Types of Anion Channels Molecularly Identified in the 2010’s

et al. 2021

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Molecular identification was, at last, successfully accomplished for three types of anion channels that are all implicated in cell volume regulation/dysregulation. LRRC8A plus LRRC8C/D/E, SLCO2A1, and TMEM206 were shown to be the core or pore-forming molecules of the volume-sensitive outwardly rectifying anion channel (VSOR) also called the volume-regulated anion channel (VRAC), the large-conductance maxi-anion channel (Maxi-Cl), and the acid-sensitive outwardly rectifying anion channel (ASOR) also called the proton-activated anion channel (PAC) in 2014, 2017, and 2019, respectively. More recently in 2020 and 2021, we have identified the S100A10-annexin A2 complex and TRPM7 as the regulatory proteins for Maxi-Cl and VSOR/VRAC, respectively. In this review article, we summarize their biophysical and structural properties as well as their physiological roles by comparing with each other on the basis of their molecular insights. We also point out unsolved important issues to be elucidated soon in the future.

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“…Electrophysiological experiments were performed as described previously 32,59,60 . Patch electrodes were fabricated from borosilicate glass capillaries using a micropipette puller (PP‐830, Narishige, Japan) and had a tip resistance of 3–5 MΩ when filled with the pipette solution.…”

Section: Methodsmentioning

confidence: 99%

Lytic and sublytic effects of gossypol on red blood cells and thymocytes

Chorieva

Fayziev

Tsiferova

et al. 2020

Clin Exp Pharma Physio

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Gossypol is a natural polyphenol presently considered as a promising biological phytochemical with a range of activities including anticancer. We examined volume regulation‐dependent effects of gossypol using erythrocytes and thymic lymphocytes. Gossypol effectively lysed human red blood cells (RBC) with a half‐maximal concentration of 67.4 ± 1.6 μmol/L and in a non‐colloid osmotic manner. Sublytic gossypol doses of 1–10 μmol/L significantly protected RBC from osmotic hemolysis, but potentiated their sensitivity to the colloid‐osmotic lysis induced by a pore‐former nystatin. When added to the thymocytes suspension, gossypol caused a strong depression of the ability of cells to restore their volume under hypoosmotic stress with a half‐maximal activity at 2.1 ± 0.3 μmol/L. Gossypol suppressed regulatory volume decrease under experimental conditions, when cationic permeability was controlled by gramicidin D, and volume recovery depended mainly on anionic conductance, suggesting that the polyphenol inhibits the swelling‐induced anion permeability. In direct patch‐clamp experiments, gossypol inhibited the volume‐sensitive outwardly rectifying (VSOR) chloride channel in thymocytes and in human HCT116 and HeLa cells, possibly by a mechanism when gossypol molecule with a radius close to the size of channel pore plugs into the narrowest portion of the native VSOR chloride channel. Micromolar gossypol suppressed proliferation of thymocytes, HCT116 and HeLa cells. VSOR blockage may represent new mechanism of anticancer activity of gossypol in addition to its action as a BH3‐mimetic.

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Tannins, novel inhibitors of the volume regulation and the volume-sensitive anion channel

Cited by 4 publications

References 47 publications

Effect of glycyrrhizin and its derivatives on integrity of human red blood cells

Effect of glycyrrhizin and its derivatives on integrity of human red blood cells

Properties, Structures, and Physiological Roles of Three Types of Anion Channels Molecularly Identified in the 2010’s

Lytic and sublytic effects of gossypol on red blood cells and thymocytes

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