Effect of Glycyrrhizic Acid and Arabinogalactan on the Membrane Potential of Rat Thymocytes Studied by Potential-Sensitive Fluorescent Probe

Glazachev, Yuri I.; Schlotgauer, Anna A.; Timoshnikov, Viktor A.; Kononova, Polina A.; Selyutina, Olga Yu.; Shelepova, Ekaterina A.; Zelikman, M. V.; Хвостов, Михаил В.; Polyakov, Nikolay E.

doi:10.1007/s00232-020-00132-3

Cited by 12 publications

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References 63 publications

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“…Glycyrrhizic acid (GA) is a triterpene glycoside extracted from licorice root that demonstrates antiviral, anti-inflammatory, and anticancer properties [37,38]. Due to its amphiphilic properties, GA is capable of forming complexes and micelles [39] with a variety of hydrophobic molecules, substantially increasing their solubility, enhancing the permeability of drugs through cell membranes and their bioavailability [12,[40][41][42][43][44][45][46]. In addition, disodium glycyrrhizin (Na 2 GA) is a salt of GA which can undergo hydrolysis in aqueous solutions and form free GA. Its advantage is that the solution formed has lower viscosity in contrast with GA solutions as far as its potassium salts are concerned.…”

Section: Introductionmentioning

confidence: 99%

Solubility, Permeability, Anti-Inflammatory Action and In Vivo Pharmacokinetic Properties of Several Mechanochemically Obtained Pharmaceutical Solid Dispersions of Nimesulide

et al. 2021

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Nimesulide (NIM, N-(4-nitro-2-phenoxyphenyl)methanesulfonamide) is a relatively new nonsteroidal anti-inflammatory analgesic drug. It is practically insoluble in water (<0.02 mg/mL). This very poor aqueous solubility of the drug may lead to low bioavailability. The objective of the present study was to investigate the possibility of improving the solubility and the bioavailability of NIM via complexation with polysaccharide arabinogalactan (AG), disodium salt of glycyrrhizic acid (Na2GA), hydroxypropyl-β-cyclodextrin (HP-β-CD) and MgCO3. Solid dispersions (SD) have been prepared using a mechanochemical technique. The physical properties of nimesulide SD in solid state were characterized by differential scanning calorimetry and X-ray diffraction studies. The characteristics of the water solutions which form from the obtained solid dispersions were analyzed by reverse phase and gel permeation HPLC. It was shown that solubility increases for all complexes under investigation. These phenomena are obliged by complexation with auxiliary substances, which was shown by 1H-NMR relaxation methods. The parallel artificial membrane permeability assay (PAMPA) was used for predicting passive intestinal absorption. Results showed that mechanochemically obtained complexes with polysaccharide AG, Na2GA, and HP-β-CD enhanced permeation of NIM across an artificial membrane compared to that of the pure NIM. The complexes were examined for anti-inflammatory activity on a model of histamine edema. The substances were administered per os to CD-1 mice. As a result, it was found that all investigated complexes dose-dependently reduce the degree of inflammation. The best results were obtained for the complexes of NIM with Na2GA and HP-β-CD. In noted case the inflammation can be diminished up to 2-fold at equal doses of NIM.

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Section: Introductionmentioning

confidence: 99%

Solubility, Permeability, Anti-Inflammatory Action and In Vivo Pharmacokinetic Properties of Several Mechanochemically Obtained Pharmaceutical Solid Dispersions of Nimesulide

et al. 2021

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“…Taking into account the data indicating the decrease in the heart pressure under the use of GA [22], one can expect the synergistic effect of using the GA-NF complex. Several It is known that glycyrrhizin forms self-associates (oligomers and micelles) in aqueous solutions, and its self-association depends on the pH of the media [32][33][34]. GA has three dissociation steps, with pKa values 3.98, 4.62, and 5.17 (Figure 1a, data is taken from [35]).…”

Section: Introductionmentioning

confidence: 99%

“…GA has three dissociation steps, with pKa values 3.98, 4.62, and 5.17 (Figure 1a, data is taken from [35]). Deprotonation of GA leads to changes in critical micelle concentration (CMC) values [32,33]. In addition, deprotonation leads to changes in the interactions of GA with lipid bilayers [33].…”

Section: Introductionmentioning

confidence: 99%

“…Deprotonation of GA leads to changes in critical micelle concentration (CMC) values [32,33]. In addition, deprotonation leads to changes in the interactions of GA with lipid bilayers [33]. Therefore, such pH-dependent behavior suggests a possible application of GA as the base of a pH-controlled drug delivery system.…”

Section: Introductionmentioning

confidence: 99%

“…Earlier, it was found in vivo, that the complexes of GA with nifedipine show a significant increase (more than one order) in its therapeutic activity on the models of adrenaline-induced hypertension and CaCl2-induced arrhythmia [36]. It is known that glycyrrhizin forms self-associates (oligomers and micelles) in aqueous solutions, and its self-association depends on the pH of the media [32][33][34]. GA has three dissociation steps, with pKa values 3.98, 4.62, and 5.17 (Figure 1a, data is taken from [35]).…”

Section: Introductionmentioning

confidence: 99%

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pH-Sensitive Glycyrrhizin Based Vesicles for Nifedipine Delivery

et al. 2021

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Glycyrrhizic acid, or glycyrrhizin (GA), a major active component of licorice root, has been widely used in traditional Chinese and Japanese medicine since ancient times. However, only in the last decades has a novel and unusual property of the GA been discovered to form water-soluble, supramolecular complexes with a variety of lipophilic drugs. These complexes show significant advantages over other known delivery systems, in particular, due to strong pH sensitivity, the properties of GA self-associates. In the present study, a supramolecular complex formation of the hypotensive and antiarrhythmic drug nifedipine with GA has been studied at different pH values, corresponding to the different degrees of GA dissociation, including a fully dissociated state of GA. Both NMR experiments and molecular dynamics simulations demonstrate the existence of the nifedipine complex with GA at all dissociation states of GA. However, optical absorption experiments show the decrease of complex stability and solubility at pH > 6 when the GA molecule is fully deprotonated. It means the higher release rate of the drug in a neutral and basic environment compared with acid media. These results could form the basis of follow-up studies of GA self-associates as pH-controlled drug delivery systems.

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Effect of glycyrrhizic acid on phospholipid membranes in media with different pH

2021

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Glycyrrhizic acid (GA) is the active ingredient in licorice root, which exhibits a wide range of biological activities, including anti-inflammatory and antiviral activities. In particular, the virus-inhibiting effect of GA on SARS-associated coronavirus was demonstrated. In addition, GA was found to be capable of increasing bioaccessibility of other drugs when used together. All these effects can be based on the ability of GA to incorporate into cell membranes and change their physical and functional properties. One of the possible mechanisms of the antiviral action of GA against COVID-19 is also considered to be the prevention of fusion of the virus envelope with the plasma membrane of the host cell. The interaction of GA with model lipid membranes was studied by the NMR method. Different factors influencing the incorporation of the GA molecule into the lipid bilayer (phospholipid structure, pH of the medium) were examined.

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Effect of Glycyrrhizic Acid and Arabinogalactan on the Membrane Potential of Rat Thymocytes Studied by Potential-Sensitive Fluorescent Probe

Cited by 12 publications

References 63 publications

Solubility, Permeability, Anti-Inflammatory Action and In Vivo Pharmacokinetic Properties of Several Mechanochemically Obtained Pharmaceutical Solid Dispersions of Nimesulide

Solubility, Permeability, Anti-Inflammatory Action and In Vivo Pharmacokinetic Properties of Several Mechanochemically Obtained Pharmaceutical Solid Dispersions of Nimesulide

pH-Sensitive Glycyrrhizin Based Vesicles for Nifedipine Delivery

Effect of glycyrrhizic acid on phospholipid membranes in media with different pH

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