Glycyrrhizin-induced changes in phospholipid dynamics studied by 1H NMR and MD simulation

Selyutina, Olga Yu.; Shelepova, Ekaterina A.; Paramonova, E.D.; Kichigina, L.A.; Халиков, С. С.; Polyakov, Nikolay E.

doi:10.1016/j.abb.2020.108368

Cited by 24 publications

(21 citation statements)

References 49 publications

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“…It is well known that surfactants were able to inactivate enveloped viruses by causing protein aggregation, disruption of the envelope, or by distorting the shape of virions [ 48 ]. At the membrane level, GA induces cholesterol-dependent disorganization of lipid rafts which are important for the entry of coronavirus into cells [ 49 , 50 ]. GA was also reported to modulate the fluidity of the plasma membrane and HIV-1 envelope [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

Glycyrrhizic Acid Inhibits SARS-CoV-2 Infection by Blocking Spike Protein-Mediated Cell Attachment

Wang

et al. 2021

Molecules

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Glycyrrhizic acid (GA), also known as glycyrrhizin, is a triterpene glycoside isolated from plants of Glycyrrhiza species (licorice). GA possesses a wide range of pharmacological and antiviral activities against enveloped viruses including severe acute respiratory syndrome (SARS) virus. Since the S protein (S) mediates SARS coronavirus 2 (SARS-CoV-2) cell attachment and cell entry, we assayed the GA effect on SARS-CoV-2 infection using an S protein-pseudotyped lentivirus (Lenti-S). GA treatment dose-dependently blocked Lenti-S infection. We showed that incubation of Lenti-S virus, but not the host cells with GA prior to the infection, reduced Lenti-S infection, indicating that GA targeted the virus for infection. Surface plasmon resonance measurement showed that GA interacted with a recombinant S protein and blocked S protein binding to host cells. Autodocking analysis revealed that the S protein has several GA-binding pockets including one at the interaction interface to the receptor angiotensin-converting enzyme 2 (ACE2) and another at the inner side of the receptor-binding domain (RBD) which might impact the close-to-open conformation change of the S protein required for ACE2 interaction. In addition to identifying GA antiviral activity against SARS-CoV-2, the study linked GA antiviral activity to its effect on virus cell binding.

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Section: Discussionmentioning

confidence: 99%

Glycyrrhizic Acid Inhibits SARS-CoV-2 Infection by Blocking Spike Protein-Mediated Cell Attachment

Wang

et al. 2021

Molecules

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“…Thymol [425] Natural polymers Lignin [426][427][428], Polyphenols [429], Cellulose [430,431], Polysialic acid [432] Gabaergic ketones Carvone, Menthone, Pulegone, Dihydrocarvone, Thujone [433] Taste and aroma Menthol [342,434], Terpenoids [435], Coumarin [132,284,436,437], Limonene [132], 4-ethylphenol (wine/beer aroma) [406], Tannins (wine) [438], Catechin [282] Caffeine and its derivatives Caffeine [132,439], Rosmarinic acid [440][441][442], Caffeic acid [441,443], Chlorogenic acid [441], Paraxanthine [132], Caffeic acid derivatives [444] Pigments Violacein [445,446], Marennine [447] Bile salts [280,423,448] Steroids Betulin [449], Saponins [450,451], Glycyrrhizic acid (saponin) [252,452,453], Withaferin-A and Withanone [454] Lipids N-arachidonylglycine and oleoyl-L-carnitine [137]...…”

Section: Antioxidantsmentioning

confidence: 99%

“…For example, glycyrrhizic acid is a saponin found in licorice root that is proposed as a potential component of drug delivery formulations, due to its ability to form complexes with a wide range of hydrophobic molecules. Using MD simulations, it has been demonstrated that glycyrrhizic acid locates inside the lipid bilayer (region 1 and 2) and significantly decreases the extent of lipid tail ordering, even at low concentration (Figure 15) [452,453]; this phenomenon could limit the pharmaceutical applications of this compound. Moreover, the gastrointestinal toxicity that has been observed in many nonsteroidal anti-inflammatory drugs, designed primarily as inhibitors of prostaglandin-endoperoxide synthase, is, at least in part, the result of the effect the drug has on membranes [687][688][689].…”

Section: Unwanted Side Effects Of Drugs Due To Their Alteration Of Membrane Propertiesmentioning

confidence: 99%

Mechanistic Understanding from Molecular Dynamics in Pharmaceutical Research 2: Lipid Membrane in Drug Design

2021

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We review the use of molecular dynamics (MD) simulation as a drug design tool in the context of the role that the lipid membrane can play in drug action, i.e., the interaction between candidate drug molecules and lipid membranes. In the standard “lock and key” paradigm, only the interaction between the drug and a specific active site of a specific protein is considered; the environment in which the drug acts is, from a biophysical perspective, far more complex than this. The possible mechanisms though which a drug can be designed to tinker with physiological processes are significantly broader than merely fitting to a single active site of a single protein. In this paper, we focus on the role of the lipid membrane, arguably the most important element outside the proteins themselves, as a case study. We discuss work that has been carried out, using MD simulation, concerning the transfection of drugs through membranes that act as biological barriers in the path of the drugs, the behavior of drug molecules within membranes, how their collective behavior can affect the structure and properties of the membrane and, finally, the role lipid membranes, to which the vast majority of drug target proteins are associated, can play in mediating the interaction between drug and target protein. This review paper is the second in a two-part series covering MD simulation as a tool in pharmaceutical research; both are designed as pedagogical review papers aimed at both pharmaceutical scientists interested in exploring how the tool of MD simulation can be applied to their research and computational scientists interested in exploring the possibility of a pharmaceutical context for their research.

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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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Glycyrrhizin-induced changes in phospholipid dynamics studied by 1H NMR and MD simulation

Cited by 24 publications

References 49 publications

Glycyrrhizic Acid Inhibits SARS-CoV-2 Infection by Blocking Spike Protein-Mediated Cell Attachment

Glycyrrhizic Acid Inhibits SARS-CoV-2 Infection by Blocking Spike Protein-Mediated Cell Attachment

Mechanistic Understanding from Molecular Dynamics in Pharmaceutical Research 2: Lipid Membrane in Drug Design

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

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