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Glycyrrhizinic acid (GA) is one of the active substances in licorice root. It exhibits antiviral activity against various enveloped viruses, for example, SARS-CoV-2. GA derivatives are promising biologically active compounds from perspective of developing broad-spectrum antiviral agents. Given that GA nicotinate derivatives (Glycyvir) demonstrate activity against various DNA- and RNA-viruses, a search for a possible mechanism of action of these compounds is required. In the present paper, the interaction of Glycyvir with the transmembrane domain of the SARS-CoV-2 E-protein (ETM) in a model lipid membrane was investigated by NMR spectroscopy and molecular dynamics simulation. The lipid-mediated influence on localization of the SARS-CoV-2 E-protein by Glycyvir was observed. The presence of Glycyvir leads to deeper immersion of the ETM in lipid bilayer. Taking into account that E-protein plays a significant role in virus production and takes part in virion assembly and budding, the data on the effect of potential antiviral agents on ETM localization and structure in the lipid environment may provide a basis for further studies of potential coronavirus E-protein inhibitors.

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Human papillomavirus (HPV), like any other virus, needs to penetrate the host cell and make use of its machinery to replicate. From there, HPV infection can be asymptomatic or lead to benign and premalignant lesions or even different types of cancer. HPV oncogenesis is due to the ability of the viral oncoproteins E6 and E7 to alter the control mechanisms for the growth and proliferation of host cell. Therefore, the use of agents with the ability to control these processes is essential in the search for effective treatments against HPV infections. Glycyrrhizinic acid (Gly), the active ingredient in liquorice, has been shown in numerous preclinical studies to have an antiviral and anticancer activity, reducing the expression of E6 and E7 and inducing apoptosis in cervical cancer cells. In addition, it also has antioxidant, anti-inflammatory, immunomodulatory or re-epithelializing properties that can be useful in HPV infections. This review includes the different antiviral and anticancer mechanisms described for Gly, as well as the clinical studies carried out that position it as a potential therapeutic strategy against HPV both through its topical application and by oral administration.

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Introducción: Los condilomas o verrugas anogenitales son secundarios a una infección causada por el virus del papiloma humano en sitios específicos, como la piel de la región anogenital, en las mucosas vaginal y anal. Es una infección de transmisión sexual rara en la edad pediátrica, muy frecuente entre los adultos y adolescentes sexualmente activos; la causa en los infantes, sin descartar el abuso sexual podría ser: 1. En el momento del parto, en la etapa neonatal y durante los primeros años; 2. Autoinoculación o hetero-inoculación de los genitales de otros niños, de adultos, familiares como la madre o cuidadores. Podría manifestarse como pequeños papilomas o crecimientos verrugosos en la piel anogenital, en la mucosa de la vagina o el ano. Este caso tiene importancia clínica ya que los tratamientos convencionales presentan recidivas a corto plazo y muchos de ellos no son bien tolerados por los pequeños pacientes. Hay tratamientos agresivos como la criocirugía; el uso de medicamentos costosos como el Imiquimod; sin embargo, las reci-divas son muy frecuentes con estos tratamientos convencionales.Objetivo: Describir el uso de un esquema de terapia de tratamiento con podofilina en combina-ción con ácido glicirricínico y ácido tricloroacético, en una paciente pediátrica con diagnóstico de condiloma ano-perineal, para ayudar a disminuir las recidivas, los costos y sobre todo los efectos psicológicos que provocan los métodos dolorosos en los pequeños pacientes. Presentación del caso: Paciente que presentó lesiones verrucosas, puntiagudos en la región ano-perineal; y, luego de haber sido intervenida en un centro de salud por varios días mediante la topicación sobre las lesiones una solución de ácido tricloro acético a 5% combinada con podofi-lina al 50%; sin embargo, el cuadro se exacerbó extendiéndose las lesiones hasta cerca del área genital. Luego de lo cual acudió a nuestra consulta, donde además de la combinación anterior, más la adición de ácido glicirricinico tópico y logrando a los 30 días la remisión de las lesiones.Conclusiones y recomendaciones: La combinación de una sustancia corrosiva, el ácido tricloro acético, con una sustancia que detiene la multiplicación celular como la podofilina; y el ácido glicirricinico el cual disminuye la replicación de los virus en un estadio temprano, impide la salida del virión de su cápside y con esto su penetración a las células. La aplicación de esta triple terapia mejoró los resultados para condilomatosis en pacientes pediátricos.

Introduction: Anogenital condylomas or warts are secondary to an infection caused by the human papillomavirus in specific sites, such as the skin of the anogenital region, in the vaginal and anal mucosa. It is a rare sexually transmitted infection in pediatric age, very common among sexually active adults and adolescents; The cause in infants, without ruling out sexual abuse, could be: 1. At the time of birth, in the neonatal stage and during the first years; 2. Autoinoculation or he-tero-inoculation of the genitals of other children, adults, family members such as the mother or caregivers. It could manifest as small papillomas or warty growths on the anogenital skin, on the mucosa of the vagina or anus. This case has clinical importance since conventional treatments present short-term recurrences and many of them are not well tolerated by young patients. There are aggressive treatments such as cryosurgery; the use of expensive medications such as Imiqui-mod; However, recurrences are very common with these conventional treatments.Objective: To describe the use of a treatment regimen with podophyllin in combination with glycyrr-hizinic acid and trichloroacetic acid, in a pediatric patient diagnosed with anoperineal condyloma, to help reduce recurrences, costs and, above all, psychological effects. that painful methods cause in young patients.Case presentation: The patient presents sharp, verrucous lesions in the ano-perineal region; and, after having been operated on in a health center for several days by topicalizing a 5% trichloroace-tic acid solution combined with 50% podophyllin on the lesions; However, the condition worsened, with the lesions extending close to the genital area. After which he came to our consultation, where in addition to the previous combination, plus the addition of topical glycyrrhizinic acid and achie-ving remission of the lesions after 30 days.Conclusions and recomendations: The combination of a corrosive substance, trichloroacetic acid, with a substance that stops cell multiplication such as podophyllin; and glycyrrhizinic acid, which decreases virus replication at an early stage, prevents the release of the virion from its cap-sid and thus its penetration into the cells. The application of this triple therapy improved the results for condylomatosis in pediatric patients.

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MOTIVATION: The monoammonium salt of glycyrrhizic acid (AGA) is known to form fibrillar hydrogels and few studies regarding self-assembly of AGA have been published. Yet, the understanding of the fibrillar microstructures and the gelation remains vague. Thus, we attempt to achieve a deeper understanding of the microstructures and the gelation process of binary solutions of AGA in water. Further, we examine the effect of ethanol on the microstructures to pave the way for potential enhancement of drug loading in AGA hydrogels. EXPERIMENTS: A partial room temperature phase map of the ternary system AGA/ethanol/water was recorded. Small-angle X-ray and neutron scattering experiments were performed over wide ranges of compositions in both binary AGA/water and ternary AGA/ethanol/water mixtures to get access to the micro-structuring. FINDINGS: Binary aqueous solutions of AGA form birefringent gels consisting of a network of long helical fibrils. 'Infinitely' long negatively charged fibrils are in equilibrium with shorter fibrils (≈25 nm), both of which have a diameter of about 3 nm and are made of around 30 stacks of AGA per helical period (≈9nm), with each stack consisting of two AGA molecules. The interaxial distance (order of magnitude ≈20 nm) varies with an almost two-dimensional swelling law. Addition of ethanol reduces electrostatic repulsion and favors the formation of fibrillar end caps, reducing the average length of shorter fibrils, as well as the formation of small, swollen aggregates. While the gel network built by the long fibrils is resilient to a significant amount of ethanol, all fibrils are finally dissolved into small aggregates above a certain threshold concentration of ethanol (≈30 wt%).

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Small ruminant lentiviruses (SRLV) infect sheep and goats resulting in significant economic losses. This study evaluated for the first time the predicted conformational structure of the SRLV-capsid-protein 25 (SRLV-p25) and analyzed the antigenicity of recombinant protein (SRLV-rp25) in mice by coupling to an immunostimulatory complexes based on glycyrrhizinic acid liposomes (GAL) and tested plasma from goats and sheep naturally infected. Analysis in silico and conformational structure of SRLV-p25 (genotype B-FESC-752) showed similar characteristics to other lentiviral capsids. The efficient expression of SRLV-rp25 was confirmed by Western blot. The humoral immune responses in mice showed an increased level of antibodies from day 21 to 35 of the SRLV-rp25-GAL and SRLV-rp25-ISCOM® groups and the cellular immune response showed no significant difference in IL-10 levels (P >.05), however, a significant difference (P <.001) was observed when comparing SRLV-rp25-GAL with SRLV-rp25 groups. Immunoreactivity toward SRLV-rp25 revealed 61% of positive samples from naturally infected goats and sheep.

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Glycyrrhizinic acid (GL) is clinically applied to treat liver injury, and the bioavailability of orally administered GL is closely related to the gut microbiota. Therefore, the dysbiosis of gut flora in liver injury could significantly influence GL bioavailability. Still, less is known about the impact of probiotic supplementation on the bio-absorption process of oral medication, especially under a pathological state. Herein, probiotic L. rhamnosus R0011 (R0011) with a high viability in the harsh gastrointestinal environment was selected, and the effect of R0011 on the GL bioavailability in rats was investigated. Four groups of rats (n = 6 per group) were included: the normal group (N group), the normal group supplemented with R0011 (NLGG group), CCl4-induced chronic liver injury model (M group), and the model group supplemented with R0011 (MLGG group). Our results showed that liver injury was successfully induced in the M and MLGG groups via an intraperitoneal injection of 50% (v/v) CCl4 solution. Healthy rats supplemented with R0011 could increase the bioavailability of GL by 1.4-fold compared with the normal group by plasma pharmacokinetic analysis. Moreover, the GL bioavailability of MLGG group was significantly increased by 4.5-fold compared with the model group. R0011 directly improved gut microbial glucuronidase and downregulated the host intestinal drug transporter gene expression of multidrug resistance protein 2 (MRP2). More critically, R0011 restored the gut microbiota composition and regulated the metabolic function, significantly enhancing the microbial tryptophan metabolic pathway compared with the pathological state, which may indirectly promote the bioavailability of GL. Overall, these data may provide possible strategies by which to address the low bioavailability of traditional medicine through probiotic intervention.

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Since the appearance of SARS-CoV-2 and the COVID-19 pandemic, the search for new approaches to treat this disease took place in the scientific community. The in silico approach has gained importance at this moment, once the methodologies used in this kind of study allow for the identification of specific protein-ligand interactions, which may serve as a filter step for molecules that can act as specific inhibitors. In addition, it is a low-cost and high-speed technology. Molecular docking has been widely used to find potential viral protein inhibitors for structural and non-structural proteins of the SARS-CoV-2, aiming to block the infection and the virus multiplication. The papain-like protease (PLpro) participates in the proteolytic processing of SARS-CoV-2 and composes one of the main targets studied for pharmacological intervention by in silico methodologies. Based on that, we performed a systematic review about PLpro inhibitors from the perspective of in silico research, including possible therapeutic molecules in relation to this viral protein. The neurological problems triggered by COVID-19 were also briefly discussed, especially relative to the similarities of neuroinflammation present in Alzheimer's disease. In this context, we focused on two molecules, curcumin and glycyrrhizinic acid, given their PLpro inhibitory actions and neuroprotective properties and potential therapeutic effects on COVID-19.

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Overabundance of extracellular matrix resulting from hyperproliferation of keloid fibroblasts (KFs) and dysregulation of apoptosis represents the main pathophysiology underlying keloids. High-mobility group box 1 (HMGB1) plays important roles in the regulation of cellular death. Suppression of HMGB1 inhibits autophagy while increasing apoptosis. Suppression of HMGB1 with glycyrrhizin has therapeutic benefits in fibrotic diseases. In this study, we explored the possible involvement of autophagy and HMGB1 as a cell death regulator in keloid pathogenesis. We have highlighted the potential utility of glycyrrhizin as an antifibrotic agent via regulation of the aberrant balance between autophagy and apoptosis in keloids. Higher HMGB1 expression and enhanced autophagy were observed in keloids. The proliferation of KFs was decreased following glycyrrhizin treatment. While apoptosis was enhanced in keloids after glycyrrhizin treatment, autophagy was significantly reduced. The expressions of ERK1/2, Akt, and NF-κB, were enhanced in HMGB1-teated fibroblasts, but decreased following glycyrrhizin treatment. The expression of extracellular matrix (ECM) components was reduced in glycyrrhizin-treated keloids. TGF-ß, Smad2/3, ERK1/2, and HMGB1 were decreased in glycyrrhizin-treated keloids. Treatment with the autophagy inhibitor 3-MA resulted in a decrease of autophagy markers and collagen in the TGF-ß-treated fibroblasts. The results indicated that autophagy plays an important role in the pathogenesis of keloids. Because glycyrrhizin appears to reduce ECM and downregulate autophagy in keloids, its potential use for treatment of keloids is indicated.

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BACKGROUND: Glycyrrhizinic acid (GA), a major active ingredient enriched in the roots of licorice, possesses well-confirmed anti-inflammatory effects. OBJECTIVE: To evaluate the underlying mechanisms of GA against lipopolysaccharide (LPS)-induced chronic neuroinflammation and memory impairment. DESIGN: We explored to investigate the effects of GA on neuroinflammation and memory impairment in an LPS-induced Alzheimer's mouse model. RESULTS: Data of micro-PET/CT imaging and morris water maze test suggested that GA, when administrated orally, could reverse LPS-induced abnormalized glucose intake and metabolism in the brain and alleviate LPS-induced memory loss and cognitive defects in mice. Histological and immunohistochemical staining results revealed that GA treatment suppressed overexpressions of pro-inflammatory cytokines of IL-1 ß and TNF-α in the brain of C57 mice by inhibiting toll-like receptor 4 (TLR4) signaling pathway activation. CONCLUSION: Our findings suggest that GA may be a therapeutic agent for the treatment of neuroinflammation and cognitive impairment.

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INTRODUCTION: Glycyrrhizinic acid is a natural product of pharmacological relevance and its anticancer activity against breast cancer cell lines has not been evaluated. Therefore the main purpose of the present study was to investigate the anticancer effects of glycyrrhizinic acid in MCF-7 human breast cancer cells. MATERIAL AND METHODS: The MTT assay was used to evaluate the anticancer effects while a clonogenic assay was used to study its effects on colony formation tendency. Flow cytometry was used to study the effects on cell cycle phase distribution and apoptosis. Western blot assay was used to study changes in protein expression of the m-TOR/PI3K/Akt pathway. RESULTS: The results indicated that glycyrrhizinic acid caused significant (p < 0.01). The growth inhibitory effects MCF-7 human breast cancer cells. The growth inhibitory effects of glycyrrhizinic acid exhibited concentration-dependent as well as time-dependent growth inhibitory trend. Different doses of glycyrrhizinic acid had a tendency to significantly (p < 0.01) inhibit the colony formation tendency of MCF-7 cells. As compared to the control group, glycyrrhizinic acid-treated cells showed a high percentage of apoptotic cells. Cells treated with a 10, 50 and 100 µM dose of glycyrrhizinic acid led to a 24.3%, 41.5% and 82.1% increase in the sub-G1 phase (apoptotic) cells. Glycyrrhizinic acid also led to significant (p < 0.01) inhibition of cell invasion along with downregulation of m-TOR/PI3K/Akt protein expression. CONCLUSIONS: Glycyrrhizinic acid inhibited MCF-7 human breast cancer cell growth and therefore may prove essential lead molecule in the treatment of breast cancer.

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A method for preparation of carboxy-protected amino acid conjugates of glycyrrhizinic acid with the use of N-hydroxybenzotriazole, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, and methyl esters of L-amino acids (phenylalanine, tyrosine, leucine, isoleucine, and methionine) in 85-90% yield was developed. The structure of the prepared compounds was confirmed by IR and 13C NMR spectra.

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La hiperplasia multiepitelial focal (HMF), se caracteriza por la aparición de lesiones múltiples en la mucosa de la cavidad bucal en población pediátrica y se asocia con la presencia del virus papiloma humano. Actualmente no existe un tratamiento de elección, el más empleado es el nitrógeno líquido (NL), pero es doloroso e incómodo para el paciente. Es por eso la necesidad de buscar nuevas alternativas de tratamiento, cuidando de ser menos invasivos, como el ácido glicirricínico (AG). Objetivo: Comparar la eficacia del AG contra el NL en la HMF en pacientes entre los 5 a 13 años de edad, en el HIM. Determinar las características clínico-epidemiológicas y los efectos adversos. Material y métodos: Ensayo clínico controlado aleatorizado. Se dividió en dos grupos. Grupo A tratado con la aplicación de AG cuatro veces al día con dos disparos del atomizador por un mes. Un grupo B tratado con NL una vez al mes por tres meses. Resultados: Se estudiaron 20 pacientes en edad pediátrica, 11 masculinos y 9 femeninos; 12 con familiares afectados. La topografía más frecuente fue el labio inferior. El grupo tratado con AG tuvo una eficacia de 63% en comparación con NL que tuvo una eficacia del 81%. Sólo se observaron efectos adversos sistémicos con NL. Se obtuvo una p de 0.075 (7.5%). Conclusiones: Se comprobó la eficacia del AG, a pesar de que fue menor que con NL. Se puede utilizar como un tratamiento coadyuvante para disminuir las lesiones, con mínimos efectos adversos locales.

In pediatric population, focal multiepithelial hyperplasia (FMH) is characterized by the onset of multiple lesions in the mucosa of the mouth; it is associated to the human papillomavirus. Presently, no special treatment is preferred, the most widely used is liquid nitrogen (LN) treatment, nevertheless, this is an uncomfortable and painful treatment for the patient. This would prompt us to look for new, less invasive treatment alternatives such as use of glycyrrhizinic acid (GA). Aim: To compare GA efficiency versus LN in FMH in Mexico Children's Hospital patients (HIM) aged 5 to 13 years. To determine clinical epidemiological characteristics as well as adverse effects. Material and methods: The present was a randomized controlled clinical trial. It was divided into two groups: group A was treated with GA applications, four times a day, two atomizer shots, for one month. Group B was treated with LN once a month for three months. Results: 20 pediatric-age patients were studied, out of which 11 were male and 9 female. 12 patients had relatives afflicted with the disease. Most frequent topography was the lower lip. Efficiency of group treated with GA was 63% when compared to group treated with LN which exhibited 81% efficiency. Systemic diverse effects were only observed with use of LN. 0.075 p was obtained (7.5%). Conclusions: GA efficiency was ascertained although it was lesser than that of LN. GA can be used as an adjuvant treatment in order to decrease lesions, it elicits minimal local adverse effects.

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Glycyrrhizin (GL), a triterpene that is present in the roots and rhizomes of licorice (Glycyrrhiza glabra), has been reported to have anti-inflammatory and anti-viral effects. Recently, we demonstrated that GL produced the neuroprotective effects with the suppression of microglia activation and proinflammatory cytokine induction in the postischemic brain with middle cerebral artery occlusion (MCAO) in rats and improved motor impairment and neurological deficits. In the present study, we investigated whether GL has a beneficial effect in kainic acid (KA)-induced neuronal death model. Intracerebroventricular (i.c.v.) injection of 0.94 nmole (0.2 µg) of KA produced typical neuronal death in both CA1 and CA3 regions of the hippocampus. In contrast, administration of GL (10 mg/kg, i.p.) 30 min before KA administration significantly suppressed the neuronal death, and this protective effect was more stronger at 50 mg/kg. Moreover, the GL-mediated neuroprotection was accompanied with the suppression of gliosis and induction of proinflammatory markers (COX-2, iNOS, and TNF-α). The anti-inflammatory and anti-excitotoxic effects of GL were verified in LPS-treated primary microglial cultures and in NMDA- or KA-treated primary cortical cultures. Together these results suggest that GL confers the neuroprotection through the mechanism of anti-inflammatory and anti-excitotoxic effects in KA-treated brain.

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Glycyrrhizin (GL), a triterpene that is present in the roots and rhizomes of licorice (Glycyrrhiza glabra), has been reported to have anti-inflammatory and anti-viral effects. Recently, we demonstrated that GL produced the neuroprotective effects with the suppression of microglia activation and proinflammatory cytokine induction in the postischemic brain with middle cerebral artery occlusion (MCAO) in rats and improved motor impairment and neurological deficits. In the present study, we investigated whether GL has a beneficial effect in kainic acid (KA)-induced neuronal death model. Intracerebroventricular (i.c.v.) injection of 0.94 nmole (0.2 microg) of KA produced typical neuronal death in both CA1 and CA3 regions of the hippocampus. In contrast, administration of GL (10 mg/kg, i.p.) 30 min before KA administration significantly suppressed the neuronal death, and this protective effect was more stronger at 50 mg/kg. Moreover, the GL-mediated neuroprotection was accompanied with the suppression of gliosis and induction of proinflammatory markers (COX-2, iNOS, and TNF-alpha). The anti-inflammatory and anti-excitotoxic effects of GL were verified in LPS-treated primary microglial cultures and in NMDA- or KA-treated primary cortical cultures. Together these results suggest that GL confers the neuroprotection through the mechanism of anti-inflammatory and anti-excitotoxic effects in KA-treated brain.

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Human papilloma virus (HPV) can infect any of the mucosal areas of the body and cause cervical cancer. Until recently, no specific treatments were available for this condition; therefore, any damaged tissue had to be removed or destroyed, which may have presented obstetrical repercussions for some women. Recently, new drugs have been developed that have shown to be effective for the cure of HPV infection. Glycyrrhizinic acid (GA) has shown fewer side effects and its systemic use makes it possible to reach difficult-to-treat lesions. The purpose of this study was to evaluate the clinical outcome of GA to eliminate the epithelial lesion and HPV. We carried out a longitudinal, descriptive study that included women of reproductive age who were diagnosed with HPV associated with low-grade squamous intraepithelial lesion (LSIL). Subjects began treatment based on GA using two routes of administration - systemic (oral) and topical (spray) - with assessments every month to determine the clinical changes of the lesions through colposcopy and Papanicolaou (Pap) smear. Simple statistics were used along with two-tailed Student's t-test; P<0.05 was considered statistically significant before and after treatment. There were 70 eligible patients, of whom 62 fulfilled the inclusion criteria. Age of subjects was 27.8±9.5 years. At the time of the study, 100% of the patients had HPV infection, 40% were associated with LSIL, and only 16% used a barrier contraceptive (condom) method. Resolution was achieved in all patients from 4 weeks of treatment initiation and improvement was achieved in the majority of patients at 12 weeks (74%) (P<0.001). However, there was persistence of LSIL in 27.7% of patients and only one patient progressed to cervical intraepithelial neoplasia (CIN) II. The use of GA proved to be effective in resolving clinical HPV lesions. For cervical lesions with epithelial changes (LSIL), treatment may be required for a longer period as with other drugs used for this infection, as well as monitoring for at least 1 year according to the natural evolution of the disease.

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Total 149 strains of endophytic bacteria were isolated from different healthy organisms of Glycyrrhiza inflata Bat. from Xinjiang. The fermented liquids of these strains were screened by TLC and analysed by HPLC, and the glycyrrhizinic acid monoammonium salt was taken as standard control at the same time. Only one endophtytic bacterial stain of Bacillus subtilis could produce Glycyrrhizinic acid monoammonium salt analogue.

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Object To optimize the extraction conditions of Fumai Decoction. Methods Uniform design test was used, and the contents of glycyrrhizinic acid and ginsenoside Rb 1 in extracted solvent were determined by HPLC. Results The ethanol volume and the extracting temperature in the uniform test impacted the test remakably. The best extraction process of Fumai Decoction as follows: the raw drugs were extracted by 10 times of 50% ethanol at 60 ℃ for 4 hours. Conclusion Glycyrrhetinic acid and ginsenoside Rb 1 contents in Fumai Decoction are higher according to the above extraction process.