Glycyrrhizic acid inhibits DNA damage repair and enhances cisplatin-induced apoptosis of melanoma cells.

This research was designed to prospect the mechanism and impact of glycyrrhizic acid (GA) on DNA damage repair and cisplatin (CP)-induced apoptosis of melanoma cells. First, human melanoma cell SK-MEL-28 was stimulated using GA for 24, 48, and 72 h. Then, the optimal treatment time and dosage were selected. After that, cell counting kit-8 (CCK-8) was employed for testing the cell viability, flow cytometry for the apoptosis, comet assay for the DNA damage of cells, and western blot for the cleaved-Caspase3, Caspase3, Bcl-2, and γH2AX protein expression levels. The experimental outcomes exhibited that as the GA concentration climbed up, the SK-MEL-28 cell viability dropped largely, while the apoptosis level raised significantly, especially at the concentration of 100 µm. In addition, compared with GA or CPtreatment only, CP combined with GA notably suppressed the viability of melanoma cells and promoted cell apoptosis at the cytological level. At the protein level, the combined treatment notably downregulated the Bcl-2 and Caspase3 expression levels, while significantly upregulated the cleaved-Caspase3 and γH2AX expression levels. Besides, CP + GA treatment promoted DNA damage at the DNA molecular level. Collectively, both GA and CP can inhibit DNA damage repair and enhance the apoptosis of SK-MEL-28 cells, and the synergistic treatment of both exhibits better efficacy.

Green Synthesis of Blumea balsamifera Oil Nanoemulsions Stabilized by Natural Emulsifiers and Its Effect on Wound Healing.

In this study, we developed a green and multifunctional bioactive nanoemulsion (BBG-NEs) of Blumea balsamifera oil using Bletilla striata polysaccharide (BSP) and glycyrrhizic acid (GA) as natural emulsifiers. The process parameters were optimized using particle size, PDI, and zeta potential as evaluation parameters. The physicochemical properties, stability, transdermal properties, and bioactivities of the BBG-NEs under optimal operating conditions were investigated. Finally, network pharmacology and molecular docking were used to elucidate the potential molecular mechanism underlying its wound-healing properties. After parameter optimization, BBG-NEs exhibited excellent stability and demonstrated favorable in vitro transdermal properties. Furthermore, it displayed enhanced antioxidant and wound-healing effects. SD rats wound-healing experiments demonstrated improved scab formation and accelerated healing in the BBG-NE treatment relative to BBO and emulsifier groups. Pharmacological network analyses showed that AKT1, CXCL8, and EGFR may be key targets of BBG-NEs in wound repair. The results of a scratch assay and Western blotting assay also demonstrated that BBG-NEs could effectively promote cell migration and inhibit inflammatory responses. These results indicate the potential of the developed BBG-NEs for antioxidant and skin wound applications, expanding the utility of natural emulsifiers. Meanwhile, this study provided a preliminary explanation of the potential mechanism of BBG-NEs to promote wound healing through network pharmacology and molecular docking, which provided a basis for the mechanistic study of green multifunctional nanoemulsions.

Combinational strategy using albumin-based nanoparticles to enable synergetic anti-rheumatic efficacy and reduced hepatotoxicity.

Methotrexate (MTX) is recognized as the golden standard for rheumatoid arthritis (RA) treatment. However, it can cause liver damage in long-term application. Although nanomedicines can target to inflamed sites, most of them tend to accumulate in liver. Glycyrrhizinic acid (GA) holds potential to reverse MTX-associated hepatotoxicity. The combination of GA and MTX might achieve a synergistic anti-inflammatory efficacy and reduced hepatotoxicity. As MTX and GA have totally different in vivo performance, it is necessary to co-encapsulate them in one carrier to coordinate their in vivo fates. Here, we co-delivered MTX and GA to arthritic joints using a human serum albumin-based nanoparticle (HSN). We found the dual drug-loaded albumin nanoparticles (HSN/MTX/GA) could preferentially distribute in inflamed joints, where GA can extend MTX retention by inhibiting the expression of efflux pumps for MTX, thereby exerting synergistic therapeutic effect. In liver tissues, GA was able to reverse the MTX-induced liver damage by activating anti-oxidant defense Nrf2/HO-1 and anti-apoptosis Bcl-2/Bax signaling. We offer a combinational strategy to effectively overcome the MTX-induced hepatotoxicity and enhance the anti-rheumatic efficacy simultaneously. Furthermore, we verified the underlying mechanism about how GA cooperated with MTX in vivo for the first time. Our findings can provide valuable insights for long-term treatment of RA.

The mechanistic interaction, aggregation and neurotoxicity of α-synuclein after interaction with glycyrrhizic acid: Modulation of synucleinopathies.

This article reveals the binding mechanism between glycyrrhizic acid (GA) and α-synuclein to may provide further information for the modulation of synucleinopathies using bioactive compounds. Therefore, the inhibitory activities of GA against α-synuclein aggregation and induced neurotoxicity were evaluated using different assays. Results showed that α-synuclein-GA binding was mediated by intermolecular hydrogen bonds leading to the formation of a slightly folded complex. Theoretical studies revealed that GA binds to the N-terminal domain of α-synuclein and triggers a compact structure around a major part of the N-terminal and the NAC regions along with fluctuations in the C-terminal domain, which are prerequisites for the inhibition of α-synuclein aggregation. Then, the cellular assays showed that GA as a potential small molecule can inhibit the oligomerization of α-synuclein and relevant neurotoxicity through modulation of neural viability, membrane leakage, and ROS formation in a concentration-dependent manner. As a result, the primary mechanism of GA's anti-aggregation and neuroprotective activities is the reorganized α-synuclein structure and fluctuating C-terminal domain, which promotes long-range transient intramolecular contacts between the N-terminal and the C-terminal domain.

In vitro and in silico investigation of glycyrrhizic acid encapsulated zein nanoparticles: A synergistic targeted drug delivery approach for breast cancer.

This study presents an innovative approach for targeted drug delivery through the development of Glycyrrhizic acid-loaded zein nanoparticles (GA-LNPs) as a proficient carrier system. The juxtaposition of zein, a hydrophobic biological macromolecule as a protein carrier, and Glycyrrhizic acid (GA), a hydrophilic therapeutic compound, exemplifies the adaptability of hydrocolloids within cutting-edge drug delivery systems. The characterization and functional traits of research encompass multifaceted analyses of natural macromolecules, which elucidate the homogeneous and spherical morphology of GA-LNPs with an average size of 170.49 nm. The controlled drug release profile of GA, orchestrated under simulated gastrointestinal conditions, adheres to diffusion-based Higuchi kinetics, reflecting the controlled release of the natural macromolecules. The intermolecular interactions among Zein, GA, and cross-linker EDC, facilitated through molecular dynamics simulations, fortify the structural integrity of the encapsulation matrix. In Vitro studies revealed enhanced cellular uptake of GA-LNPs in MCF-7 breast cancer cells. This cellular internalization was further confirmed through cytotoxicity assessments using MTT and apoptosis assays (fluorescence microscopy), which demonstrated the prominent anticancer effects of GA-LNPs on MCF-7 in time/dose-dependent manner. The successful formulation of GA-LNPs, coupled with their sustained release and potent anticancer properties, makes them a potential platform for advanced targeted therapeutic strategies in biomedical applications.

Network pharmacology and in vitro experimental verification unveil glycyrrhizin from glycyrrhiza glabra alleviates acute pancreatitis via modulation of MAPK and STAT3 signaling pathways.

Acute pancreatitis (AP) is a severe gastrointestinal inflammatory disease with increasing mortality and morbidity. Glycyrrhiza glabra, commonly known as Liquorice, is a widely used plant containing bioactive compounds like Glycyrrhizin, which possesses diverse medicinal properties such as anti-inflammatory, antioxidant, antiviral, and anticancer activities. The objective of this study is to investigate the active components, relevant targets, and underlying mechanisms of the traditional Chinese medicine Glycyrrhiza glabra in the treatment of AP. Utilizing various computational biology methods, we explored the potential targets and molecular mechanisms through Glycyrrhizin supplementation. Computational results indicated that Glycyrrhizin shows promising pharmacological potential, particularly with mitogen-activated protein kinase 3 (MAPK3) protein (degree: 70), forming stable complexes with Glycyrrhizin through ionic and hydrogen bonding interactions, with a binding free energy (ΔGbind) of -33.01 ± 0.08 kcal/mol. Through in vitro experiments, we validated that Glycyrrhizin improves primary pancreatic acinar cell injury by inhibiting the MAPK/STAT3/AKT signaling pathway. Overall, MAPK3 emerges as a reliable target for Glycyrrhizin's therapeutic effects in AP treatment. This study provides novel insights into the active components and potential targets and molecular mechanisms of natural products.

Development and Evaluation of a Novel Hyaluronic Acid and Chitosan-modified Phytosome for Co-delivery of Oxymatrine and Glycyrrhizin for Combination Therapy.

BACKGROUND: Multidrug resistance (MDR) of cancer cells is a major obstacle to efficient cancer chemotherapy. Combination therapy is expected to enhance the anticancer effect and reverse MDR. Numerous patents involve different kinds of nanoparticles for the co-delivery of multiple chemotherapeutics, but the FDA has approved none. OBJECTIVE: In this study, oxymatrine (OMT) and glycyrrhizin (GL) were co-loaded into phytosomes as the core of nanocarriers, and the shell was cross-linked with chitosan (CS) and hyaluronic acid (HA) with the capability for the controlled, sequential release and the targeted drug uptake. METHODS: Phospholipid complexes of OMT and GL (OGPs) were prepared by a solvent evaporation technique and could self-assemble in an aqueous solution to form phytosomes. CS and HA were sequentially coated on the surface of OGPs via electrostatic interactions to obtain CS coated OGPs (CS-OGPs) and HA modified CS-OGPs (HA-CS-OGPs), respectively. The particle size and zeta potential were measured to optimize the formulations. In vitro cytotoxicity and cellular uptake experiments on HepG2 cells were performed to evaluate the anticancer activity. RESULTS: OGPs were obtained with nano-size around 100 nm, and CS and HA coating on phytosomes could change the particle size and surface potential. The drug loading of OMT and GL showed that the nanocarriers could maintain a fixed ratio of 1:1. The in vitro release experiments indicated the release of OMT and GL was pH-dependent and sequential: the release of OMT from CS-OGPs and HA-CS-OGPs was significantly increased at pH 5.0 compared to the release at pH 7.4, while GL exhibited sustained released from CS-OGPs and HA-CS-OGPs at pH 5.0. Furthermore, in vitro cytotoxicity and cellular uptake experiments on HepG2 cells demonstrated that the co-delivery system based on phytosomes had significant synergistic anti-tumor activities, and the effects were enhanced by CS and HA modification. CONCLUSION: The delivery of OMT and GL via HA-CS-OGPs might be a promising treatment to reverse MDR in cancer therapy.

[Adverse effects of licorice consumed as food: An update]. / Toxicités de l'exposition alimentaire à la réglisse : mise au point.

The word "licorice" refers to the plant, its root, and its aromatic extract. From a commercial point of view, Glycyrrhiza glabra is the most important species with a wide range of uses (herbal medicine, tobacco industry, cosmetics, food and pharmaceutical). Glycyrrhizin is one of the main constituents of licorice. Glycyrrhizin is hydrolyzed in the intestinal lumen by bacterial ß-glucuronidases to 3ß-monoglucuronyl-18ß-glycyrrhetinic acid (3MGA) and 18ß-glycyrrhetinic acid (GA), which are metabolized in the liver. Plasma clearance is slow due to enterohepatic cycling. 3MGA and GA can bind to mineralocorticoid receptors with very low affinity, and 3MGA induces apparent mineralocorticoid excess syndrome through dose-dependent inhibition of 11ß-hydroxysteroid dehydrogenase type 2 in renal tissue. The cases of apparent mineralocorticoid excess syndrome reported in the literature are numerous and sometimes severe, even fatal, most often in cases of chronic high dose consumption. Glycyrrhizin poisonings are characterized by hypertension, fluid retention, and hypokalemia with metabolic alkalosis and increased kaliuresis. Toxicity depends on the dose, the type of product consumed, the mode of consumption (acute or chronic) and a very large inter-individual variability. The diagnosis of glycyrrhizin-induced apparent mineralocorticoid excess syndrome is based on the history, clinical examination, and biochemical analysis. Management is primarily based on symptomatic care and stopping licorice consumption.

Improving meat qualities of pigs after deworming against ascariasis with administered glycyrrhizic acid.

The present paper describes the effect of glycyrrhizic acid contained in licorice roots on the quality of pork produced. The study uses advanced research methods as ion-exchange chromatography, inductively coupled plasma mass spectrometry, drying of an average sample of muscle, and pressing method. The paper set out to investigate the effect of glycyrrhizic acid on the pig meat quality after deworming. Of particular concern is the animal body restoration after deworming that results in metabolic disorders. The nutrient content of meat reduces, the output of bones and tendons rises. This is the first report on the use of glycyrrhizic acid to increase the meat quality of pigs after deworming. The findings from this study indicated higher pork quality resulted from a favorable effect of GA on the chemical and amino acid composition of meat. The resulting data demonstrated that glycyrrhizic acid in the piglets' diet had a beneficial effect on the biochemical processes in their body. The main scientific provisions of this paper and its findings have several practical implications for veterinary specialists. They can also be recommended for the educational process. Another possible implication is the development of new drugs, methods, and treatment plans.

The tissue distribution of Jinzhen oral liquid in healthy and influenza mice.

Jinzhen oral liquid (JZOL) is widely used in China. However, its tissue distribution, a vital part of the efficacy substances research, has not been reported yet. This study characterized its chemical components and its prototypes and metabolites in mice, and investigated its tissue distribution in pathological and healthy mice. Several constituents were characterized, including 55 constituents in JZOL, 11 absorbed prototypes and six metabolites in plasma and tissues. The metabolic pathways were demethylation, dehydration and acetylation. A sensitive, accurate and stable quantitative method was established and applied to the tissue distribution. After administration of JZOL, these seven components were rapidly distributed to various tissues, mainly staying in the small intestine, and less distributed to lung, liver and kidney. Compared with healthy mice, the absorption of baicalin, wogonoside, rhein, glycyrrhizic acid and liquiritin apioside was reduced in influenza mice, but their elimination was slow. However, influenza infection had no obvious effect on the overall distribution of the most important components (baicalin, glycyrrhizic acid and wogonoside) in the plasma or small intestine, but obviously affected the distribution of baicalin in liver. In summary, seven components are rapidly distributed to various tissues, and influenza infection has certain influence on the tissue distribution of JZOL.

Potential of glycyrrhizic and glycyrrhetinic acids against influenza type A and B viruses: A perspective to develop new anti-influenza compounds and drug delivery systems.

Despite the recent dynamic development of medicine, influenza is still a significant epidemiological problem for people around the world. The growing resistance of influenza viruses to currently available antiviral drugs makes it necessary to search for new compounds or drug forms with potential high efficacy against human influenza A and B viruses. One of the methods of obtaining new active compounds is to chemically modify privileged structures occurring in the natural environment. The second solution, that is gaining more and more interest, is the use of modern drug carriers, which significantly improve physicochemical and pharmacokinetic parameters of the transported substances. Molecules known from the earliest times for their numerous therapeutic properties are glycyrrhizinic acid (GA) and glycyrrhetinic acid (GE). Both compounds constitute the main active agents of the licorice (Glycyrrhiza glabra, Leguminosae) root and, according to a number of scientific reports, show antiviral properties against both DNA and RNA viruses. The above information prompted many scientific teams around the world to obtain and test in vitro and/or in vivo new synthetic GA and GE derivatives against influenza A and B viruses. Similarly, in recent years, a significant amount of GA and GE-based drug delivery systems (DDS) such as nanoparticles, micelles, liposomes, nanocrystals, and carbon dots has been prepared and tested for antiviral activity, including those against influenza A and B viruses. This work systematizes the attempts undertaken to study the antiviral activity of new GA and GE analogs and modern DDS against clinically significant human influenza viruses, at the same time indicating the directions of their further development.

Controlled flavor release from high internal phase emulsions as fat mimetics based on glycyrrhizic acid and phytosterol.

Animal fat as the key component of sensory experience impacts texture, juiciness, and aroma pleasantness of meat, which indicates the necessity of designing fat mimetics in meat alternatives. In this study, high internal phase emulsions (HIPE) with tunable flavor release as fat mimetics based on glycyrrhizic acid (GA) and phytosterol were prepared, and the effects of GA and phytosterol concentrations on the microstructural, rheological, and flavor release properties of HIPE were evaluated. Phytosterol crystals-enriched oil droplets were trapped inside the GA fibrillar matrix as stabilizers. HIPE containing higher GA and phytosterol concentrations exhibited smaller droplet size and better viscoelastic attributes. Additionally, phytosterol played a synergistic role with GA to form a double-fiber microstructure at the oil-water interface. This hierarchical microstructure of oil phase, interface and aqueous phase in the HIPE could regulate the release of hydrophilic and lipophilic meat volatiles. HIPE as fat mimetics with unique microstructure have potential applications in meat alternatives.

Thermoresponsive Dual-Structured Gel Emulsions Stabilized by Glycyrrhizic Acid Nanofibrils in Combination with Monoglyceride Crystals.

Responsive dual-structured emulsions and gel emulsions have attracted more and more attention due to their complex microstructures, on-demand responsive properties, and controlled release of active cargoes. In this work, the effect of monoglyceride (MG)-based oil phase structuring on the formation and stability, structural properties, and thermoresponsive and cargo release behavior of gel emulsions stabilized by glycyrrhizic acid (GA) nanofibrils were investigated. Owing to the formation of GA fibrillar networks in the aqueous phase and MG crystalline networks in the oil phase, a stable dual-structured gel emulsion can be successfully developed. The microstructure of the dual-structured gel emulsions largely depended on the concentration of MG in the oil phase. At low MG concentrations (1-2 wt%), the larger formed and lamellar MG crystals may pierce the interfacial fibrillar film, inducing the formation of partially coalesced droplets. In contrast, at high MG concentrations (4 wt% or above), the smaller MG crystals with enhanced interfacial activity can lead to the formation of a bilayer shell of GA nanofibrils and MG crystals, thus efficiently inhibiting the interfacial film damage and forming a jamming structure with homogeneously distributed small droplets. Compared to pure GA nanofibril gel emulsions, the GA-MG dual-structured gel emulsions showed significantly improved mechanical performance as well as good thermoresponsive behavior. Moreover, these stable GA-MG gel emulsions can be used as food-grade delivery vehicles for encapsulating and protecting hydrophobic and hydrophilic bioactive cargoes. They also have great potential as novel and efficient aroma delivery systems showing highly controlled volatile release. The dual-structured emulsion strategy is expected to broaden the applications of natural saponin GA-based gel emulsions in the food, pharmaceutical, and personal care industries.

Synthesis and In Vitro Study of Antiviral Activity of Glycyrrhizin Nicotinate Derivatives against HIV-1 Pseudoviruses and SARS-CoV-2 Viruses.

When developing drugs against SARS-CoV-2, it is important to consider the characteristics of patients with different co-morbidities. People infected with HIV-1 are a particularly vulnerable group, as they may be at a higher risk than the general population of contracting COVID-19 with clinical complications. For such patients, drugs with a broad spectrum of antiviral activity are of paramount importance. Glycyrrhizinic acid (Glyc) and its derivatives are promising biologically active compounds for the development of such broad-spectrum antiviral agents. In this work, derivatives of Glyc obtained by acylation with nicotinic acid were investigated. The resulting preparation, Glycyvir, is a multi-component mixture containing mainly mono-, di-, tri- and tetranicotinates. The composition of Glycyvir was characterized by HPLC-MS/MS and its toxicity assessed in cell culture. Antiviral activity against three strains of SARS-CoV-2 was tested in vitro on Vero E6 cells by MTT assay. Glycyvir was shown to inhibit SARS-CoV-2 replication in vitro (IC502-8 µM) with an antiviral activity comparable to the control drug Remdesivir. In addition, Glycyvir exhibited marked inhibitory activity against HIV pseudoviruses of subtypes B, A6 and the recombinant form CRF63_02A (IC50 range 3.9-27.5 µM). The time-dependence of Glycyvir inhibitory activity on HIV pseudovirus infection of TZM-bl cells suggested that the compound interfered with virus entry into the target cell. Glycyvir is a promising candidate as an agent with low toxicity and a broad spectrum of antiviral action.

Robust and highly adaptable high internal phase gel emulsions stabilized solely by a natural saponin hydrogelator glycyrrhizic acid.

Herein, we report a new class of high internal phase gel emulsions (gel-HIPEs) that are mechanically robust, adaptable, and processable. They can be synthesized facilely by using the natural food-grade saponin glycyrrhizic acid (GA) as the sole stabilizer, which is shown to be versatile for various oils. The structural properties of these HIPEs including appearance, viscoelasticity and processability are well controlled by simply changing the concentration of GA nanofibrils. When the GA nanofibril concentration exceeds 0.3 wt%, the unique gel-HIPEs can be produced through the formation of fibrillar hydrogel networks in the continuous phase. When the nanofibril concentration only increases to 5 wt%, it is surprising to see that these gel-HIPEs display an extremely high mechanical strength, and the storage moduli as well as the yield stress values can reach 408.5 kPa and 3340 Pa (or even more), respectively. We conjecture that such remarkable mechanical performance is mainly attributed to the highly viscoelastic GA nanofibrillar networks in the continuous phase of gel-HIPEs, which can actively trap the nanofibril-coated emulsion droplets and thus strengthen the gel matrix. Consequently, the robust gel-HIPEs can be used as a solid template to fabricate stable porous materials without the need for crosslinking of the continuous phase, and the open- and closed-cell foam microstructures are controlled by the nanofibril concentration. Furthermore, the nanofibril-based HIPEs are promising long-term delivery vehicles with controlled-release properties for lipophilic active cargoes, since the strong fibrillar networks at the droplet surfaces and in the continuous phase can effectively retard the active release.

A novel biomimetic nanomedicine system with anti-inflammatory and anti-osteoporosis effects improves the therapy efficacy of steroid-resistant nephrotic syndrome.

Clinically, steroid-resistant nephrotic syndrome (SRNS) is always prolonged and difficult to treat and easily develops into end-stage renal disease, resulting in a low survival rate. Strategies to reverse steroid resistance and reduce the long-term use of high doses of steroid medicines are urgently needed. In this study, a novel nanoparticle drug system (Pm-GCH) with a core-shell structure was designed. Metal-organic frameworks, synthesized by glycyrrhizic acid (G) and calcium ions (Ca2+) loaded with hydrocortisone (H) were the core of the nanoparticles. Platelet membrane vesicles were the shells. The natural platelet membrane endows Pm-GCH with good biocompatibility and the ability to promote immune escape. In addition, under the chemotaxis of inflammatory factors, platelet membranes assist Pm-GCH in nonspecific targeting of the inflammatory sites of the kidney. Under an inflammatory acid environment, GCH slowly degrades and releases glycyrrhizic acid and hydrocortisone. Glycyrrhizic acid inhibits the inactivation of hydrocortisone, jointly inhibits the activity of phospholipase A2 (PLA2) and the classic activation pathway of complement C2, blocks the production of inflammatory factors, plays an anti-inflammatory role, and enhances the efficacy of hydrocortisone in the treatment of SRNS. Moreover, glycyrrhizic acid alleviates osteoporosis induced by long-term use of glucocorticoids. These results indicate that Pm-GCH is a promising treatment strategy for SRNS.

Strengthened rebamipide ocular nanoformulation to effectively treat corneal alkali burns in mice through the HMGB1 signaling pathway.

Corneal alkali burns are a major ophthalmic emergency, as current therapeutic treatments are limited. Novel treatment targets and new potential agents are required to combat this severe ocular injury. Glycyrrhizin and rebamipide (RBM) are both FDA-approved drugs with potential effects against corneal alkali burns, but RBM is limited by its low aqueous solubility and low bioavailability. This study aimed to utilize dipotassium glycyrrhizinate (DG, a dipotassium salt of glycyrrhizin) as a nanocarrier encapsulating RBM to formulate an ophthalmic solution (marked DG-RBM) with strengthened activities to treat corneal alkali burns. Results showed that an easy DG-RBM preparative process generated particles with high encapsulation efficacy and ultra-small micellar size. The solubility of RBM in DG-RBM in aqueous solution was 3.1 × 105-fold enhanced than its free solution. DG-RBM exhibited excellent storage stability. In vitro cytotoxicity, ex vivo conjunctival responses, and rabbit eye tolerance tests showed that DG-RBM possessed good ocular safety profiles. DG-RBM exhibited improved in vivo corneal permeation profiles and demonstrated a strong effect against H2O2-induced oxidative damage, with a significant effect on promoting epithelial wound healing in corneal cells in vitro. As expected, in a mouse model of corneal alkali burns, the topical administration of DG-RBM achieved a strengthened efficacy against alkali burn damages. The mechanism of this therapeutic effect involved regulating high-mobility group box 1 (HMGB1) signaling and its related angiogenic and proinflammatory cytokines. These findings demonstrate the ease of preparing DG-RBM and its great potential as a novel ocular topical formulation to treat corneal alkali burns by regulating HMGB1 signaling.

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

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.

Recent Advances and Applications of Plant-Based Bioactive Saponins in Colloidal Multiphase Food Systems.

The naturally occurring saponins exhibit remarkable interfacial activity and also possess many biological activities linking to human health benefits, which make them particularly attractive as bifunctional building blocks for formulation of colloidal multiphase food systems. This review focuses on two commonly used food-grade saponins, Quillaja saponins (QS) and glycyrrhizic acid (GA), with the aim of clarifying the relationship between the structural features of saponin molecules and their subsequent self-assembly and interfacial properties. The recent applications of these two saponins in various colloidal multiphase systems, including liquid emulsions, gel emulsions, aqueous foams and complex emulsion foams, are then discussed. A particular emphasis is on the unique use of GA and GA nanofibrils as sole stabilizers for fabricating various multiphase food systems with many advanced qualities including simplicity, ultrastability, stimulability, structural viscoelasticity and processability. These natural saponin and saponin-based colloids are expected to be used as sustainable, plant-based ingredients for designing future foods, cosmetics and pharmaceuticals.

Stable DOPG/Glycyrrhizin Vesicles with a Wide Range of Mixing Ratios: Structure and Stability as Seen by Scattering Experiments and Cryo-TEM.

Phosphatidylglycerols represent a large share of the lipids in the plasmamembrane of procaryotes. Therefore, this study investigates the role of charged lipids in the plasma membrane with respect to the interaction of the antiviral saponin glycyrrhizin with such membranes. Glycyrrhizin is a natural triterpenic-based surfactant found in licorice. Vesicles made of 1,2-dioleoyl-sn-glycero-3-phospho-rac-(1'-glycerol) (DOPG)/glycyrrhizin are characterized by small-angle scattering with neutrons and X-rays (SANS and SAXS). Small-angle scattering data are first evaluated by the model-independent modified Kratky-Porod method and afterwards fitted by a model describing the shape of small unilamellar vesicles (SUV) with an internal head-tail contrast. Complete miscibility of DOPG and glycyrrhizin was revealed even at a ratio of lipid:saponin of 1:1. Additional information about the chain-chain correlation distance of the lipid/saponin mixtures in the SUV structures is obtained from wide-angle X-ray scattering (WAXS).