Down-regulation of abaI, abaR, Bap and OmpA genes in Acinetobacter baumannii by ethanol extract of Glycyrrhiza glabra after toxicity assessment.

Acinetobacter baumannii is a pathogen that has caused rising concerns within healthcare facilities in recent years. As antibiotic overuse and resistance rise, natural remedies with the potential have received attention as antibiotics that might have fewer side effects and lower resistance. Glycyrrhiza glabra was used to investigate its effects on A. baumannii's quorum sensing and biofilm production abilities. In this study, the toxicity assessment of Glycyrrhiza glabra L. extract on rats, the phytochemical analysis and the quantitative measurement for the association of the biofilm reduction with the active components in the plant was determined. The results indicated ciprofloxacin and gentamicin were the most effective antibiotics and that various capabilities of biofilm-productions were demonstrated, only four percent of the samples established robust biofilm, while 40% to 56% demonstrated weak to moderate biofilm production, respectively. Phytochemical qualitative testing of ethanol leaf extracts from Glycyrrhiza glabra showed the existence of flavonoids, alkaloids, phenolic, tannic acid, and terpenoids, but no saponins. Assessment of toxicity revealed a low hazard, with an LD50 of 4.95 g/Kg. Our results showed that the extract's SICs elucidated a substantial quantitative decrease in biofilm production by the bacterial isolates, including the reference ATCC strain, which is known to be a potent biofilm producer. As a conclusion, biofilm creation in Acinetobacter baumannii has been shown to be greatly reduced by G. glabra extract.

Assessment on the photocatalytic and phytotoxic activities using ecobenevolently synthesized iron oxide nanoparticles from the root extracts of Glycyrrhiza glabra.

The present study is the first attempt to utilize the root extracts of Glycyrrhiza glabra as a novel biological route for the synthesis of iron oxide nanoparticles (Fe2O3NPs) under optimized conditions. The process variables namely concentration of ferric chloride, root extract of G. glabra and temperature were optimized using Response Surface Methodology (RSM) to obtain high yield. Phytochemicals mediated the reduction process and served as capping and stabilizing agent. The biosynthesized Fe2O3NPs characterized using UV-Vis spectroscopy exhibited a prominent peak at 350 nm. The crystallinity and valence state of Fe2O3NPs was confirmed by XRD and XPS. The surface functionalization of the nanoparticles was confirmed from the presence of functional groups in the FT-IR spectrum. The FESEM analysis revealed the biosynthesized Fe2O3NPs are irregular and the EDX spectrum recorded the presence of iron and oxygen in the synthesized nanoparticles. The biosynthesized Fe2O3NPs exhibited an appreciable photocatalytic activity against methylene blue under sunlight with a maximum decolorisation efficiency of 92% within 180 min of reaction time. The experimental data of adsorption studies well fitted with Langmuir isotherm and pseudo-second order kinetic model. The thermodynamic study proved to be spontaneous, feasible and endothermic in nature. The phytotoxicity study revealed 92% germination and increased seedling growth in the green gram seeds exposed to Fe2O3NPs. Hence the study established the efficiency of biosynthesized of Fe2O3NPs in photocatalytic and phytotoxic activities.

Assessment of Herb-Drug Interaction Potential of Five Common Species of Licorice and Their Phytochemical Constituents.

The dried roots and rhizomes of Glycyrrhiza species (G. glabra, G. uralensis and G. inflata), commonly known as licorice, have long been used in traditional medicine. In addition, two other species, G. echinata and G. lepidota are also considered "licorice" in select markets. Currently, licorice is an integral part of several botanical drugs and dietary supplements. To probe the botanicals' safety, herb-drug interaction potential of the hydroethanolic extracts of five Glycyrrhiza species and their key constituents was investigated by determining their effects on pregnane X receptor, aryl hydrocarbon receptor, two major cytochrome P450 isoforms (CYP3A4 and CYP1A2), and the metabolic clearance of antiviral drugs. All extracts enhanced transcriptional activity of PXR and AhR (>2-fold) and increased the enzyme activity of CYP3A4 and CYP1A2. The highest increase in CYP3A4 was seen with G. echinata (4-fold), and the highest increase in CYP1A2 was seen with G. uralensis (18-fold) and G. inflata (16-fold). Among the constituents, glabridin, licoisoflavone A, glyasperin C, and glycycoumarin activated PXR and AhR, glabridin being the most effective (6- and 27-fold increase, respectively). Licoisoflavone A, glyasperin C, and glycycoumarin increased CYP3A4 activity while glabridin, glyasperin C, glycycoumarin, and formononetin increased CYP1A2 activity (>2-fold). The metabolism of antiretroviral drugs (rilpivirine and dolutegravir) was increased by G. uralensis (2.0 and 2.5-fold) and its marker compound glycycoumarin (2.3 and 1.6-fold). The metabolism of dolutegravir was also increased by G. glabra (2.8-fold) but not by its marker compound, glabridin. These results suggest that licorice and its phytochemicals could affect the metabolism and clearance of certain drugs that are substrates of CYP3A4 and CYP1A2.Supplemental data for this article is available online at https://doi.org/10.1080/19390211.2022.2050875 .

Analysis of international competitiveness of the China's licorice industry from the perspective of global trade.

ETHNOPHARMACOLOGICAL RELEVANCE: Licorice is a multi-purpose plant raw material, which is widely used in the pharmaceutical industry and food industry, cosmetic industry, etc. It has a wide application in various countries and regions around the world. AIM OF STUDY: This paper studied the trade situation of licorice-related products among major countries and regions in the world, providing a practical reference for the sustainable development of the global licorice industry. MATERIALS AND METHODS: The licorice trade data of licorice-related products came from the United Nations Commodity Trade Database and China Customs data. We analyzed the world's major trading countries by using international market share (IMS), trade competitiveness index (TC), average export price (AEP) and average import price (AIP), and analyzed global trade flows with chord diameter. RESULTS: Uzbekistan, Kazakhstan and Iran mainly export licorice raw materials and low value-added products. China is both a producer and a consumer of licorice raw materials and licorice products. The processing trade of the licorice industry in China has advantages, and the structure of import and export trade has been continuously improved. The United States, France, Germany and other developed countries are still important consumers who rely on the intellectual property rights and brand advantages of licorice products, which have stronger global trade radiation capacity. CONCLUSIONS: China's trade structure has been optimized and its industrial competitiveness has been enhanced. China's experience can be used for reference by other countries, especially those with rich licorice resources among the SCO members.

Quality assessment of fried licorice based on fingerprints and chemometrics.

Fried licorice is obtained by frying licorice without using any auxiliary materials, and it is widely used both as food and medicine in China. To explore the influence of licorice origin on the quality of fried licorice, a method based on fingerprinting and chemometrics was developed. Twenty batches of licorice were selected from four locations. The reference chromatograms of each location were established via similarity analysis. Chemometric methods, such as cluster, principal component, and orthogonal partial least squares discriminant analyses were used to evaluate the changes in the composition of fried licorice, predict its origin, and reflect its quality. Mass spectrometry was used to identify the chemical components. Finally, an origin prediction function was established via discriminant analysis to trace the origin of licorice. The model was demonstrated to be stable, reliable, and accurate in predicting licorice origin and to provide a reference for origin traceability.

Quality assessment of licorice (Glycyrrhiza glabra L.) from different sources by multiple fingerprint profiles combined with quantitative analysis, antioxidant activity and chemometric methods.

Licorice, as a nutritional plant extensively used in food fields, grows in various origins of the world as wild and cultivated types. But existing methods were not adequate for quality estimation of licorice samples from multiple sources till date. In the present research, HPLC, UV and FT-IR were applied together to establish fingerprint profiles of licorice (Glycyrrhiza glabra L.) samples. Then, an appropriate quantitative method was adopted to evaluate their qualities. Furthermore, eight active chemical compositions and the potential antioxidant capacities of licorice samples were determined, and their intrinsic characteristics were excavated by chemometric methods. The results showed that the ingredient content and antioxidant capacity of licorice were closely related to the origin and growth type, and the established method was capable of accurately classifying wild and cultivated licorice samples from nine habitats into five quality grades. This study provides a novel and comprehensive strategy for food quality assessment.

Antibacterial Activity of Glycyrrhiza Glabra Roots against food-borne bacterial pathogens / Actividad Antibacteriana de la Raíz de Glycyrrhiza glabra Contra las Bacterias Patógenas Transmitidas por los Alimentos

ABSTRACT Objective: The antibacterial activity of Glycyrrhiza glabra (Liquorice) roots was evaluated against several food-borne bacterial pathogens. Methods: The in vitro anti-bacterial activity was evaluated by determining the zone diameter of inhibition (ZDI), minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) using the aqueous. Ethanolic and methanolic extracts of the roots of Glycyrrhiza glabra. Results: Therefore, significant increase in inhibitory feature was observed because of increase in extracts concentration. In addition, the aqueous extract was more effective than the others; while, among the tested bacteria, Staphylococcus aureus and Pseudomonas aeruginosa were the most sensitive and the most resistant, respectively. Conclusion: Extracts of Glycyrrhiza glabra roots can potentially be used in the pharmaceutical and food industries as preservatives or antimicrobial agents.

RESUMEN Objetivo: La actividad antibacteriana del extracto de raíces de Glycyrrhiza glabra (regaliz) fue evaluada frente a varias bacterias patógenas trasmitidas por los alimentos. Métodos: La actividad antimicrobiana se evalúa determinando el diámetro de la zona de inhibición (DZI), y la concentración bactericida mínima (CBM). Extractos acuosos, etanólicos y metanólicos de la raíz de Glycyrrhiza glabra fueron analizados en su actividad antibacteriana in vitro. Resultados: Por lo tanto, se observó un aumento significativo en la característica inhibitoria debido al aumento en la concentración de extractos. Además, el extracto acuoso fue más eficaz que los otros, en tanto que, entre las bacterias probadas, Staphylococcus aureus y Pseudomonas aeruginosa fueron las más sensibles y las más resistentes, respectivamente. Conclusión: Los resultados sugieren que los extractos de raíz de Glycyrrhiza glabra tienen un uso potencial en la industria farmacéutica y alimentaria, y pueden ser útiles como conservantes o agentes antimicrobianos.

Incompatibility assessment of Genkwa Flos and Glycyrrhizae Radix et Rhizoma with biochemical, histopathological and metabonomic approach.

ETHNOPHARMACOLOGICAL RELEVANCE: As recorded in traditional Chinese medicine (TCM) theory, Genkwa Flos (YH) and Glycyrrhizae Radix et Rhizoma (GC) compose one herbal pair of the so-called "eighteen incompatible medicaments", which indicate pairs of herbs that are mutually incompatible and that theoretically should not be applied simultaneously. However, the theory has been called into question due to a lack of evidence. AIMS OF STUDY: In this study, the incompatibility of YH and GC was investigated based on an assessment of the toxic effects of their combination by traditional safety methods and a modern metabonomic approach. MATERIALS AND METHODS: Sprague-Dawley rats were used to evaluate the subacute toxicity of YH and YH-GC. The serum, urine, and several tissues were collected for biochemical analysis, histopathological examination, and metabonomic analysis. RESULTS: Rats exposed to a dose of 1.0 g/kg YH (3 times of the Chinese Pharmacopoeia maximum dose) exhibited toxicity of the heart, liver, kidney and testes, and rats exposed to a YH-GC combination (1.0 g/kg YH + 1.0 g/kg GC) exhibited similar hepatotoxicity, which aggravated renal and reproductive toxicity. Following this, a metabonomic study tentatively identified 14 potential biomarkers in the YH group and 10 potential biomarkers in the YH-GC group, and metabolic pathways were then constructed. YH disturbed the pathways of glycerophospholipid metabolism, primary bile acid biosynthesis, and sphingolipid metabolism, while YH-GC combination induced disruptions in phenylalanine, tyrosine and tryptophan biosynthesis, tyrosine metabolism, and glycerophospholipid metabolism. CONCLUSION: The toxicities of YH and YH-GC combination above the Chinese Pharmacopoeia dose were obvious but different. Metabonomics combined with biochemical and histopathological methods can be applied to elucidate the toxicity mechanism of the YH-GC combination that caused liver, kidney and reproductive injuries in rats.

Direct assessment of adherence and drug interactions in patients with hypertensive crisis-A cross-sectional study in the Emergency Department.

Though drug adherence is supposed to be low in hypertensive crisis (HTN-C), there are no data available from direct adherence assessments. The aim of the present study was to evaluate adherence to prescribed antihypertensives and potential interactions of concomitant drugs and foods with prescribed antihypertensives in patients with HTN-C by a direct evaluation via biochemical urine analysis. In the present cross-sectional study, 100 patients with HTN-C, admitted to the emergency department (ED), were included. A biochemical urine analysis using gas chromatography-tandem mass spectrometry was performed. Out of 100 patients, 86 received antihypertensives. Urine analyses could be evaluated unambiguously in 62 patients. In 15 of these 62 patients (24%), a nonadherence could be demonstrated, and in 21 patients (34%), a partial nonadherence could be demonstrated. Patients with nonadherence or partial nonadherence showed a longer hypertension history (15[5-22] vs 10[3-15] years, P = 0.04) were prescribed more general medication (number 7.1 ± 3.4 vs 3.4 ± 1.8; P < 0.01) as well as antihypertensive drugs (number 2.8 ± 1.1 vs 1.5 ± 0.7, P < 0.01). A potential BP-raising trigger by medications or food interaction was frequently detectable, predominantly with nonsteroidal anti-inflammatory drugs (NSAIDs; n = 38), glucocorticoids (n = 8), antidepressants (n = 10), and licorice (n = 10). Nonadherence and partial nonadherence to prescribed antihypertensives might play a crucial role for the occurrence of HTN-C. However, further case-controlled studies are needed to confirm the present findings. Ingestion of concurrent over-the-counter drugs such as NSAIDs but also prescribed drugs as well as aliments may lead to critical BP elevation. In order to prevent HTN-C, the present findings emphasize the importance for clinicians to pay attention to the issue of adherence and co-medication.

Review - Glycyrrhiza glabra L. (Liquorice).

Medicinal plants are being used for treating various diseases. According to World Health Organization 80% of the world population depends on indigenous medicinal plant remedies. Herbal medicine employs fruits, vegetables, as dry materials or their extracts for the treatment of different diseases and health maintenance. Glycyrrhiza glabra (Liquorice) has been used in Europe since prehistoric times. It is well documented in written form starting with the ancient Greeks. Glycyrrhizin is the major active constituent obtained from liquorice roots, one of the most widely used in herbal preparations for the treatment of liver complaints. The plant is used as anti-inflammatory, spasmolytic, laxative, anti-depressive, anti-ulcer and anti-diabetic. The present review focuses Glycyrrhiza glabra distribution, ethno botany, ethno pharmacology, chemical constituents, medicinal uses, cultivation and trade. Plant requires a lot of attention as it has been reduced in population due to over-use in Baluchistan. The plant conservationists should consider this herb as priority species and should start its cultivation on the commercial scale to fulfill the requirements of the local markets and pharmaceutical industries as well as reduce the pressure on the wild plants.

The use of botanical products and vitamins in sunscreens.

The use of botanical products and vitamins in skin care creams and sunscreens is prevalent. Herein we conduct an evaluation of sunscreens to quantitatively assess how often sunscreens incorporate botanically derived products and vitamins. The most commonly used botanicals products and vitamins are identified and stratified based on the sunscreen sun protection factor (SPF). The overall prevalence for the use of botanical agents and vitamins was 62% and 79%, respectively. Aloe vera and licorice root extracts were the most common botanical agents used in sunscreens. Retinyl palmitate was the most common vitamin derivative utilized in sunscreens. The prices of sunscreens significantly increased when more than one botanical product was added. Botanical products and vitamins are widely utilized in sunscreens and more research is needed to assess how their inclusion may enhance or alter the function of sunscreens.

An integrated exact mass spectrometric strategy for comprehensive and rapid characterization of phenolic compounds in licorice.

RATIONALE: Licorice (Gancao) is derived from the dried roots and rhizomes of Glycyrrhiza species (Leguminosae) and appears as a component herb in about 60% of traditional Chinese medicine (TCM) prescriptions. Modern pharmacological studies have shown that flavonoids are one class of the major components responsible for the bioactivities of licorice. Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC/QTOF MS) has proven to be a powerful tool for rapid profiling and identification of natural products in complex herbal medicines. METHODS: A UPLC/QTOF MS method was established for the first time for profiling and structural characterization of the phenolic compounds (most of them flavonoids) in licorice. The combined use of data-independent acquisition (MS(E) ) and data-dependent acquisition (DDA) was illustrated. RESULTS: Fifteen flavonoid reference compounds were used to explore the fragmentation pathways. Compound identification was based upon the exact mass, general fragmentation behaviors, retention times, UV absorption, and the related botanical biogenesis. As a result, a total of 51 compounds were characterized, three of which were reported for the first time. CONCLUSIONS: The LC/MS analysis for each injection took less than 9 min. The developed method is fast, accurate and reliable due to its high resolution and high efficiency characteristics as a result of combining both UPLC separation and QTOF exact mass measurement.

Licorice-related rhabdomyolysis: a big price for a sweet tooth.

UNLABELLED: A 50-year-old lady on hydrochlorothiazide (HCTZ) presented to the hospital after 4 days of generalized muscle aches and dark urine. She admitted to consuming one and a half bags of black licorice bites containing 2% natural licorice during the past 3 weeks. Examination showed high blood pressure, while labs revealed elevated creatine kinase, hypokalemia, hypocalcemia and hypophosphatemia with low aldosterone and plasma renin levels and high intact PTH. The active component of licorice is glycyrrhizic acid, which inhibits an enzyme required to convert cortisol to a less active metabolite, cortisone. This causes excess cortisol, simulating syndrome of apparent mineralocorticoid excess (AME), thus resulting in hypertension, hypokalemia and metabolic alkalosis. In our patient, licorice induced hypokalemia resulted in rhabdomyolysis. The rhabdomyolysis along with the effect of licorice led to secondary hypocalcaemia, which in turn triggered secondary hyperparathyroidism. This might have had a phosphaturic effect that caused hypophosphatemia, further worsening rhabdomyolysis. CONCLUSION: This case illustrates the complex relationship of various electrolytes, which can lead to self perpetuation of the disease, hence demanding more vigilance.

Dispersive solid-phase extraction cleanup combined with accelerated solvent extraction for the determination of carbamate pesticide residues in Radix Glycyrrhizae samples by UPLC-MS-MS.

Dispersive solid-phase extraction (DSPE) cleanup combined with accelerated solvent extraction (ASE) is described here as a new approach for the extraction of carbamate pesticides in Radix Glycyrrhizae samples prior to UPLC-MS-MS. In the DSPE-ASE method, 15 carbamate pesticides were extracted from Radix Glycyrrhizae samples with acetonitrile by the ASE method at 60 °C with a 5 min heating time and two static cycles. Cleanup of a 1 mL aliquot of the extract by the DSPE method used 20 mg PSA (primary secondary amine), 50 mg Al(2)O(3)-N, and 20 mg GCB (graphitized carbon black) (as cleanup sorbents) under the determined optimum conditions. The linearity of the method was in the range of 10 to 200 ng/mL with correlation coefficients (r(2)) of more than 0.996. The limits of detection were approximately 0.2 to 5.0 µg/kg. The method was successfully used for the analysis of target pesticides in Radix Glycyrrhizae samples. The recoveries of the carbamate pesticides at the spiking levels of 50, 100, and 200 µg/kg ranged from 79.7% to 99.3% with relative standard deviations lower than 10%. This multi-residue analytical method allows for a rapid, efficient, sensitive and reliable determination of target pesticides in Radix Glycyrrhizae and other medicinal herbs.

Overall qualitative and overall quantitative assessment of compound liquoric tablets using HPLC fingerprints.

So far, there has been no advanced method to assure quality control for herbal drugs (HD) and traditional Chinese medicines (TCM). Because HD and TCM have been becoming more and more important for human health, it is necessary to set up an effective quality control method in terms of overall qualitative and overall quantitative analyses for them. In this study, the HPLC fingerprints (HPLC-FPs) of compound liquoric tablets (CLTs) were established to effectively control their qualities by using the dual qualitative and dual quantitative similarities (DQDQS) method, in which 13 batches of CLTs synthesized the referential FP (RFP) as a norm. Among the 26 batches of CLTs, 11 batches were assessed as completely qualified, the contents of 3 batches were obviously higher while the contents of other 6 batches were lower; the chemical constituents proportion distributed in 1 batch were not qualified and the remaining 5 batches were inferior. HD and TCM can be authentically evaluated by this method.

Survey of Glycyrrhizae Radix resources in Mongolia: chemical assessment of the underground part of Glycyrrhiza uralensis and comparison with Chinese Glycyrrhizea Radix.

In order to reveal the chemical characteristics of Glycyrrhiza uralensis growing in Mongolia and to clarify whether it can be the source of Glycyrrhizae Radix used in Japan, eight major bioactive constituents in the underground parts of G. uralensis collected in Mongolia were quantitatively analyzed and compared with Glycyrrhizae Radix produced in China. Most of the 15 samples from eastern, southern and western parts of Mongolia contained 26.95-58.55 mg/g of glycyrrhizin, exceeding the criterion (25 mg/g) assigned in the Japanese Pharmacopoeia. The sample collected in Tamsagiyn hooly, Dornod province, in eastern Mongolia was of the highest content 58.55 mg/g. The contents of three flavanone constituents (liquiritin apioside, liquiritin and liquiritigenin) and three chalcones (isoliquiritin apioside, isoliquiritin and isoliquiritigenin) varied significantly according to collection places; the subtotal of the three flavanones ranged from 3.00 to 26.35 mg/g, and the subtotal of the three chalcones ranged from 1.13 to 10.50 mg/g. The content of glycyrrhizin and subtotal contents of flavanones and chalcones in the underground parts of G. uralensis from Mongolia were obviously lower than wild samples, but higher than cultivated samples derived from the same species produced in China. Glycycoumarin, a species-specific constituent of G. uralensis, was detected in all Mongolian samples. Its contents in samples from eastern Mongolia, Sergelen and Tamsagiyn hooly of Dornod province were very high and were compatible with Tohoku-kanzo derived from wild Chinese G. uralensis. The present study suggested that Mongolian G. uralensis could be a source of Glycyrrhizae Radix, mostly of Japanese Pharmacopoeia grade. However, the producing area should be taken into consideration to ensure relatively high quality. In addition, planned use and promotion of cultivation must be advocated to avoid confronting Mongolian Glycyrrhiza with the same threat as its congener in China. Our study sheds some light on selecting cultivation areas and superior strains, which are important tasks to promote cultivation.

[Enhance technique researches on Glycyrrhiza industries, promote three-dimensional rural economic development in three-north areas].

OBJECTIVE: To analyze the current situation about Glycyrrhiza resources, summarize the research achievements on Glycyrrhiza relative industries, and indentify the importance of developing Glycyrrhiza industries to promote the three-dimensional rural economic development in the Three-North areas. METHOD: Literatures and documents were referred to, in combination with overview and analysis of the outcomes and achievements of our group. RESULT AND CONCLUSION: The gap between supply and demand of resources is enlarged continuously. To develop high-quality Glycyrrhiza cultivation is the most powerful and effective measure to protect wild resources and the environment and promote the three-dimensional rural economic development in the Three-North areas.

Final report on the safety assessment of Glycyrrhetinic Acid, Potassium Glycyrrhetinate, Disodium Succinoyl Glycyrrhetinate, Glyceryl Glycyrrhetinate, Glycyrrhetinyl Stearate, Stearyl Glycyrrhetinate, Glycyrrhizic Acid, Ammonium Glycyrrhizate, Dipotassium Glycyrrhizate, Disodium Glycyrrhizate, Trisodium Glycyrrhizate, Methyl Glycyrrhizate, and Potassium Glycyrrhizinate.

Glycyrrhetinic Acid and its salts and esters and Glycyrrhizic Acid and its salts and esters are cosmetic ingredients that function as flavoring agents or skin-conditioning agents - miscellaneous or both. These chemicals may be isolated from licorice plants. Glycyrrhetinc Acid is described as at least 98% pure, with 0.6% 24-OH-Glycyrrhetinic Acid, not more than 20 mu g/g of heavy metals and not more than 2 mu g/g of arsenic. Ammonium Glycyrrhizate has been found to be at least 98% pure and Dipotassium Glycyrrhizate has been found to be at least 95% pure. Glycyrrhetinic Acid is used in cosmetics at concentrations of up to 2%; Stearyl Glycyrrhetinate, up to 1%; Glycyrrhizic Acid, up to 0.1%; Ammonium Glycyrrhizate, up to 5%; Dipotassium Glycyrrhizate, up to 1%; and Potassium Glycyrretinate, up to 1%. Although Glycyrrhizic Acid is poorly absorbed by the intestinal tract, it may be hydrolyzed to Glycyrrhetinic Acid by a beta -glucuronidase produced by intestinal bacteria. Glycyrrhetinic Acid and Glycyrrhizic Acid bind to rat and human albumin, but do not absorb well into tissues. Glycyrrhetinic Acid and Glycyrrhizic Acid and metabolites are mostly excreted in the bile, with very little excreted in urine. Dipotassium Glycyrrhizate was undetectable in the receptor chamber when tested for transepidermal permeation through pig skin. Glycyrrhizic Acid increased the dermal penetration of diclofenac sodium in rat skin. Dipotassium Glycyrrhizate increased the intestinal absorption of calcitonin in rats. In humans, Glycyrrhetinic Acid potentiated the effects of hydrocortisone in the skin. Moderate chronic or high acute exposure to Glycyrrhizic Acid, Ammonium Glycyrrhizate, and their metabolites have been demonstrated to cause transient systemic alterations, including increased potassium excretion, sodium and water retention, body weight gain, alkalosis, suppression of the renin-angiotensis-aldosterone system, hypertension, and muscular paralysis; possibly through inhibition of 11beta -hydroxysteroid dehydrogenase-2 (11beta -OHSD2) in the kidney. Glycyrrhetinic Acid and its derivatives block gap junction intracellular communication in a dose-dependent manner in animal and human cells, including epithelial cells, fibroblasts, osteoblasts, hepatocytes, and astrocytes; at high concentrations, it is cytotoxic. Glycyrrhetinic Acid and Glycyrrhizic Acid protect liver tissue from carbon tetrachloride. Glycyrrhizic Acid has been used to treat chronic hepatitis, inhibiting the penetration of the hepatitis A virus into hepatocytes. Glycyrrhetinic Acid and Glycyrrhizic Acid have anti-inflammatory effects in rats and mice. The acute intraperitoneal LD(50) for Glycyrrhetinic Acid in mice was 308 mg/kg and the oral LD(50) was > 610 mg/kg. The oral LD(50) in rats was reported to be 610 mg/kg. Higher LD(50) values were generally reported for salts. Little short-term, subchronic, or chronic toxicity was seen in rats given ammonium, dipotassium, or disodium salts of Glycyrrhizic Acid. Glycyrrhetinic Acid was not irritating to shaved rabbit skin, but was considered slightly irritating in an in vitro test. Glycyrrhetinic Acid inhibited the mutagenic activity of benzo[a]pyrene and inhibited tumor initiation and promotion by other agents in mice. Glycyrrhizic Acid inhibited tumor initiation by another agent, but did not prevent tumor promotion in mice. Glycyrrhizic Acid delayed mortality in mice injected with Erlich ascites tumor cells, but did not reduce the mortality rate. Ammonium Glycyrrhizate was not genotoxic in in vivo and in vitro cytogenetics assays, the dominant lethal assay, an Ames assay, and heritable translocation tests, except for possible increase in dominant lethal mutations in rats given 2000 mg/kg day(-1) in their diet. Disodium Glycyrrhizate was not carcinogenic in mice in a drinking water study at exposure levels up to 12.2 mg/kg day(-1) for 96 weeks. Glycyrrhizate salts produced no reproductive or developmental toxicity in rats, mice, golden hamsters, or Dutch-belted rabbits, except for a dose-dependent increase (at 238.8 and 679.9 mg/kg day(-1)) in sternebral variants in a study using rats. Sedation, hypnosis, hypothermia, and respiratory depression were seen in mice given 1250 mg/kg Glycyrrhetinic Acid intraperitoneally. Rats fed a powdered diet containing up to 4% Ammonium Glycyrrhizate had no treatment related effects in motor function tests, but active avoidance was facilitated at 4%, unaffected at 3%, and depressed at 2%. In a study of 39 healthy volunteers, a no effect level of 2 mg/kg/day was determined for Glycyrrhizic Acid given orally for 8 weeks. Clinical tests in seven normal individuals given oral Ammonium Glycyrrhizate at 6 g/day for 3 days revealed reduced renal and thermal sweat excretion of Na+ and K+, but carbohydrate and protein metabolism were not affected. Glycyrrhetinic Acid at concentrations up to 6% was not a skin irritant or a sensitizer in clinical tests. Neither Glycyrrhizic Acid, Ammonium Glycyrrhizate, nor Dipotassium Glycyrrhizate at 5% were phototoxic agents or photosensitizers. Birth weight and maternal blood pressure were unrelated to the level of consumption of Glycyrrhizic Acid in 1049 Finnish women with infants, but babies whose mother consumed > 500 mg/wk were more likely to be born before 38 weeks. The Cosmetic Ingredient Review (CIR) Expert Panel noted that the ingredients in this safety assessment are not plant extracts, powders, or juices, but rather are specific chemical species that may be isolated from the licorice plant. Because these chemicals may be isolated from plant sources, however, steps should be taken to assure that pesticide and toxic metal residues are below acceptable levels. The Panel advised the industry that total polychlorobiphenyl (PCB)/pesticide contamination should be limited to not more than 40 ppm, with not more than 10 ppm for any specific residue, and that toxic metal levels must not contain more than 3 mg/kg of arsenic (as As), not more than 0.002% heavy metals, and not more than 1 mg/kg of lead (as Pb). Although the Panel noted that Glycyrrhizic Acid is cytotoxic at high doses and ingestion can have physiological effects, there is little acute, short-term, subchronic, or chronic toxicity and it is expected that these ingredients would be poorly absorbed through the skin. These ingredients are not considered to be irritants, sensitizers, phototoxic agents, or photosensitizers at the current maximum concentration of use. Accordingly, the CIR Expert Panel concluded that these ingredients are safe in the current practices of use and concentration. The Panel recognizes that certain ingredients in this group are reportedly used in a given product category, but the concentration of use is not available. For other ingredients in this group, information regarding use concentration for specific product categories is provided, but the number of such products is not known. In still other cases, an ingredient is not in current use, but may be used in the future. Although there are gaps in knowledge about product use, the overall information available on the types of products in which these ingredients are used and at what concentration indicate a pattern of use. Within this overall pattern of use, the Expert Panel considers all ingredients in this group to be safe.

Determination of glycyrrhizin in liqueurs by on-line coupled capillary isotachophoresis with capillary zone electrophoresis.

An on-line coupled capillary isotachophoresis-capillary zone electrophoresis method for the determination of glycyrrhizin in liqueurs is described. The optimised electrolyte system was 5 mM HCl+11 mM epsilon-aminocaproic acid+0.05% hydroxyethylcellulose+30% methanol (leading electrolyte), 5 mM caproic acid+30% methanol (terminating electrolyte) and 20 mM caproic acid+10 mM histidine+0.1% hydroxyethylcellulose+30% methanol (background electrolyte). Method characteristics, i.e., linearity (20-500 ng/ml), accuracy (recovery 99+/-4%), intra-assay repeatability (2%), intermediate repeatability (3.8%) and detection limit (8 ng/ml) were determined. Speed of analysis, low laboriousness, high sensitivity and low-running cost are the typical attributes of the capillary isotachophoresis-capillary zone electrophoresis method. Developed method was successfully applied to analysis of liqueurs with liquorice extract and some foods (sweets and food supplements) containing liquorice. Found levels of glycyrrhizin in liqueurs, sweets and food supplements varied between 1-16 mg/l, 850-1050 mg/kg and 1.6-1.8 g/kg, respectively.

Risk and safety assessment on the consumption of Licorice root (Glycyrrhiza sp.), its extract and powder as a food ingredient, with emphasis on the pharmacology and toxicology of glycyrrhizin.

Licorice (or 'liquorice') is a plant of ancient origin and steeped in history. Licorice extracts and its principle component, glycyrrhizin, have extensive use in foods, tobacco and in both traditional and herbal medicine. As a result, there is a high level of use of licorice and glycyrrhizin in the US with an estimated consumption of 0.027-3.6 mg glycyrrhizin/kg/day. Both products have been approved for use in foods by most national and supranational regulatory agencies. Biochemical studies indicate that glycyrrhizinates inhibit 11beta-hydroxysteroid dehydrogenase, the enzyme responsible for inactivating cortisol. As a result, the continuous, high level exposure to glycyrrhizin compounds can produce hypermineralocorticoid-like effects in both animals and humans. These effects are reversible upon withdrawal of licorice or glycyrrhizin. Other in vivo and clinical studies have reported beneficial effects of both licorice and glycyrrhizin consumption including anti-ulcer, anti-viral, and hepatoprotective responses. Various genotoxic studies have indicated that glycyrrhizin is neither teratogenic nor mutagenic, and may possess anti-genotoxic properties under certain conditions. The pharmacokinetics of glycyrrhizin have been described and show that its bioavailability is reduced when consumed as licorice; this has hampered attempts to establish clear dose-effect levels in animals and humans. Based on the in vivo and clinical evidence, we propose an acceptable daily intake of 0.015-0.229 mg glycyrrhizin/kg body weight/day.