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PubMed2005

[Study on circumscription of medicinal licorice species based on molecular biology].

OBJECTIVE: Elucidate the medicinal licorice species circumscription in order to develop licorice resources in China and select new cultivars. METHOD: PCR amplification, DNA sequencing and cladistic analysis. RESULT: Acquire the ITS sequences and phylogenetic tree of 8 licorice species. CONCLUSION: According to results Glycyrrhiza eurycarpa and G. glabra var. glandulosa should be combined into G. and G. glabra respectively and G. egladulosa is an independent species.

Base Sequence↗
PubMed1989

Oral baicalin and liquid extract of licorice reduce sorbitol levels in red blood cell of diabetic rats.

Intracellular accumulation of sorbitol, resulting from the increased glucose flux through polyol pathway with the action of aldose reductase, has been found pathogenic to chronic diabetic complications. It has been reported that baicalin and Glycyrrhiza uralensis Fisch can inhibit rat lens aldose reductase in vitro. In order to determine whether the said medicinal herbs give the inhibitive effect in vivo, 10 streptozotocin induced diabetic rats were treated with baicalin 150 mg/kg.d and liquid extract of licorice (LEL) 7.5 ml/kg.d for a week. RBC sorbitol was determined by a fluorometric assay before and after the treatment, as well as one week afterwards. It was found that oral baicalin and licorice dramatically reduced sorbitol levels in RBC without affecting blood glucose levels. The sorbitol levels was restored to its original values one week after discontinuing the treatment. The present study has demonstrated the effectiveness of baicalin and licorice in reducing RBC sorbitol levels in diabetic rats. Its mechanism is presumably through inhibition of aldose reductase. The feasibility of its clinical application for the control of diabetic complications is under investigation.

Animals↗
PubMed1982

Licorice consumption among high school students.

A survey was carried out of licorice intake among 603 4th and 5th form pupils of two Dunedin high schools. Licorice was eaten on a regular (weekly) basis by 29 percent of the girls and 17 percent of the boys. At least 200 g (of black licorice confectionery) was eaten weekly by 5.9 percent of the girls and 4.9 percent of the boys; at least 500 g was eaten weekly by 1.8 percent of the girls and I percent of the boys. The intake reported by two pupils exceeded 1000 g per week.

Adolescent↗
PubMed1995

[Acute rhabdomyolysis and tetraparesis secondary to hypokalemia due to ingested licorice].

The glycirrinic acid, a common component of the natural licorice, has a potent mineralacorticoid effect (primary pseudohyperaldosteronism) which may cause severe hypokalemia and acute rhabdomyolysis. We present the case of a 36-years-old patient who, as the result of the intake of five daily licorice sticks (25 gr/day) for one month, developed analytical and clinical signs of acute rhabdomyolysis associated to the typical disorders of mineralcorticoid excess, that is, severe hypokalemia, arterial hypertension and metabolic alkalosis. The relevance of this clinical case lies on the low frequency of this finding and on the need that physicians working at emergency care centers must be aware of the onset of acute tetraparesis related to hypokalemia secondary to licorice ingesta. The early detection of this pathology is essential, since it will result in the beginning of an specific treatment, avoiding thus, as far as possible, the severe complications that might appear.

Acute Disease↗
PubMed1997

In vitro antiviral activity of indigenous glycyrrhizin, licorice and glycyrrhizic acid (Sigma) on Japanese encephalitis virus.

Glycyrrhizin, a triterpenoid glycoside and Licorice from Glycyrrhiza glabra and Ammonium salt of Glycyrrhizic acid (Sigma) were tested for antiviral activity on three strains of Japanese encephalitis virus (JEV), Nakayama, P-20778 and 821564 XY48. Purified glycyrrhizin (M.w. 822.92) inhibited plaque formation in all the three strains of JEV at a concentration of 500 micrograms/ml at 96 hrs, Similar effect was observed at 1000 micrograms/ml concentration with Licorice and Ammonium salt of glycyrrhizic acid. The minimal inhibitory concentrations were not toxic to porcine stable kidney (PS) and human cervical carcinoma (HeLa) cell lines. Cyctotoxicity of these chemicals was evaluated by trypan blue dye exclusion test which indicated subtoxic concentrations at 5,000 micrograms/ml at 96 hrs and toxic concentrations were 10,000 micrograms/ml at the same time period for the host cells PS. Thus the indigenously purified glycyrrhizin seems to be more potent antiviral agent than Licorice and ammonium salt of glycyrrhizic acid (Sigma) for JEV 'in vitro'.

Antiviral Agents↗
PubMed1985

Anticariogenic activity of licorice and glycyrrhizine I: Inhibition of in vitro plaque formation by Streptococcus mutans.

The effect of licorice and its active sweet component glycyrrhizin was tested on the growth and adherence to glass of the cariogenic Streptococcus mutans. Neither licorice nor glycyrrhizin promoted growth or induced plaque formation. In the presence of sucrose, glycyrrhizin did not affect bacterial growth, but the adherence (plaque formation) was markedly inhibited. At 0.5-1% glycyrrhizin, inhibition was almost complete. These results support our previous suggestions that glycyrrhizin might serve as an efficient vehicle for topical oral medications.

Anti-Bacterial Agents↗
PubMed1983

Hypokalemic rhabdomyolysis with myoglobinuria due to licorice ingestion and diuretic treatment.

A 54-year-old man was admitted to hospital with acute rhabdomyolysis and myoglobinuria due to hypokalemia. The hypokalemia was due to chronic licorice ingestion and diuretic treatment. The myoglobinemia led to a glomerulopathy and tubulopathy. There was, however, no clinical evidence of acute renal failure (ARF). We propose that the volume expansion caused by the steroid-like actions of licorice might have prevented the development of an ARF.

Diuretics↗
PubMed2005

An on-membrane quantitative analysis system for glycyrrhizin in licorice roots and traditional Chinese medicines.

An on-membrane quantitative analysis system has been developed for determining glycyrrhizin (GC) in licorice roots and traditional Chinese medicines. A GC standard and the extracts of licorice roots and traditional Chinese medicines were applied to a polyethersulfone (PES) membrane and were developed by acetonitrile/water/formic acid (45:55:2, by volume), then treated with a NaIO4 solution followed by bovine serum albumin (BSA), resulting in a GC-BSA conjugate on a PES membrane. Anti-GC monoclonal antibody was bound and then a second antibody labeled with peroxidase directed against the first antibody. Finally a substrate reacted with the enzyme and gave staining. The stained membrane was scanned and coloring spots were analyzed quantitatively using graphic analysis by NIH Image software, indicating at least 0.5 microg of GC was clearly detectable. GC can be analyzed quantitatively between 1.0 and 8.0 microg.

Chromatography, High Pressure Liquid↗
PubMed2005

Effect of licorice root on peripheral blood indexes upon vibration exposure.

We studied the effect of continuous vibration and treatment with licorice root (Glycyrrhiza glabra L.) on peripheral blood red cells in rabbits. Active substances of licorice root accelerated metabolism in cells of the bone marrow erythroid stem, enhanced compensatory reserve of the organism, and increased animal's resistance to stress.

Animals↗
PubMed2004

Pharmacokinetic and pharmacodynamic profiles of the antitussive principles of Glycyrrhizae radix (licorice), a main component of the Kampo preparation Bakumondo-to (Mai-men-dong-tang).

We examined the pharmacokinetic and pharmacodynamic properties of liquiritin apioside, a main antitussive component of Glycyrrhizae radix (licorice), with regard to its antitussive effect in guinea pigs. The peak plasma concentration of the unchanged compound was observed 15 min after the administration of liquiritin apiosaide. The plasma concentration then gradually decreased and was almost undetectable 4 h after administration. Liquiritigenin, a des-glycoside of liquiritin apioside, appeared in the plasma 2 h after the administration of liquiritin apioside and remained for more than 6 h after administration. The plasma concentration of unchanged liquiritigenin was observed 15 min after administration and then gradually increased for more than 6 h after administration. When the antitussive effects of liquiritin apioside, liquiritin and liquiritigenin, at respective doses of 30 mg/kg, p.o., were examined 1 h after administration, liquiritin apioside and liquiritigenin caused a significant reduction in the number of capsaicin-induced coughs. However, at the same dose, liquiritin had no significant effect on the number of capsaicin-induced coughs. On the other hand, when the antitussive effects of liquiritin apioside, liquiritin and liquiritigenin, at doses of 30 mg/kg, p.o., were examined 4 h after administration, each caused a more than 40% reduction in the number of capsaicin-induced coughs. The present results suggest that G. radix (licorice) may produce a persistent antitussive effect, and that liquiritin apioside plays an important role in the earlier phase, while liquiritigenin, which is a metabolite of liquiritin apioside and liquiritin, plays an important role in the late phase.

Animals↗
PubMed1998

Effect of licorice and glycyrrhizin on murine liver CYP-dependent monooxygenases.

This study is aimed to investigate the effect of the prolonged intake of conspicuous amounts of licorice (LE), or its natural constituent glycyrrhizin (G) on murine liver CYP-catalyzed drug metabolism. For this purpose the modulation of the regio- and stereo-selective hydroxylation of testosterone, together with the use of highly specific substrates as probes for different CYP isoforms such as ethoxyresorufin (CYP1A1), methoxyresorufin (1A2), pentoxyresorufin (2B1), p-nitrophenol (2E1) and aminopyrine (3A), were investigated. Daily doses of licorice root extract (3,138 or 6,276 mg/kg b.w. per os), or G (240 or 480 mg/kg b.w. per os), were administered to different groups of Swiss Albino CD1 mice of both sexes for 1, 4 or 10 consecutive days. While a single LE or G dose was unable to affect the multienzymatic CYP-system, using both schedules of repeated treatment, either LE or G were able to significantly induce hepatic CYP3A- and, to a lesser extent, 2B1- and 1A2-dependent microsomal monooxygenase activities, as well as 6beta- (mainly associated to CYP3A), 2alpha-, 6alpha- (CYP2A1, 2B1), 7alpha-, 16alpha- (CYP2B9) and 16beta-testosterone hydroxylase (TH) activities in male and female mice. Data on CYP3A modulation, the major isoform present in human liver, was confirmed by using Western immunoblotting with anti-CYP3A1/2 rabbit polyclonal antibodies raised against purified rat CYP3A. Northern blotting analysis using CYP3A cDNA biotinylated probe showed that the expression of such isozyme is regulated at the mRNA level. These results suggest that the induction of cytochrome P450-dependent activities by the prolonged intake of high LE or G doses, may result in accelerated metabolism of coadministered drugs with important implications for their disposition. The adverse effects associated with CYP changes such as toxicity/cotoxicity and comutagenicity may also have clinical consequences.

Animals↗
PubMed1997

Enzymic O-methylation of isoliquiritigenin and licodione in alfalfa and licorice cultures.

S-Adenosyl-L-methionine (SAM): isoliquiritigenin (2',4,4'-trihydroxychalcone) 2'-O-methyltransferase (CHMT) of alfalfa (Medicago sativa) catalyses the formation of 4,4'-dihydroxy-2'-methoxychalcone, which is the most potent inducer of nodulation-genes of Rhizobium meliloti, the symbiont of alfalfa which forms nitrogen-fixing nodules. SAM: licodione 2'-O-methyltransferase (LMT) is involved in the biosynthesis of a retrochalcone in cultured licorice (Glycyrrhiza echinata) cells and has been shown to be induced as a defence response of the cells. Because licodione exists in an equilibrium mixture of tautomeric 2',4,4',beta-tetrahydroxychalcone (major) and 1-(2,4-dihydroxyphenyl)-3-(4-hydroxyphenyl)-1,3-propanedione (minor), the apparent mode of action of both enzymes is very similar. In this study, cultured alfalfa cells were shown to exhibit rapid and transient increases in the extractable activities of both CHMT and LMT after treatment with yeast extract (YE). Treatment of solution-cultured alfalfa seedlings with YE also resulted in a similar induction of both CHMT and LMT activities in the roots, but no activity was detected in the shoots. These activities were attributed to a single gene product, the CHMT protein, as extracts of Escherichia coli transformed with the CHMT cDNA exhibited both CHMT and LMT activities. In contrast, in G. echinata cells, LMT was induced after YE treatment, but no CHMT activity was observed. It is concluded that alfalfa CHMT and licorice LMT are distinct enzymes, the former displaying the wider substrate specificity.

Chalcone↗
PubMed2003

Licorice-induced hypokalemia as a treatable cause of dropped head syndrome.

Isolated weakness of the extensor muscles of the neck is a relatively rare condition, known as "dropped head syndrome" (DHS). This paper reports the case of a patient with DHS whose symptoms resolved rapidly on supplementation with potassium and discontinuation of licorice consumption. To the best of our knowledge, there are no reports in the literature of DHS due to licorice-induced hypokalemia.

Aged↗
PubMed1997

Antioxidant constituents from licorice roots: isolation, structure elucidation and antioxidative capacity toward LDL oxidation.

The present study analyzed the antioxidative properties of natural compounds from the root of the plant Glycyrrhiza glabra (licorice) toward LDL oxidation. Seven constituents, with antioxidant capacity were isolated from Glycyrrhiza glabra. The isolated compounds were identified as the isoflavans Hispaglabridin A (1), Hispaglabridin B (4), Glabridin (3), and 4'-O-Methylglabridin (2), the two chalcones, isoprenylchalcone derivative (5) and Isoliquiritigenin (6), and the isoflavone, Formononetin (7). Among these compounds, Glabridin constituted the major amount in the crude extract (11.6%, w/w) as detected by high-performance liquid chromatography (HPLC) analysis. The antioxidative capacities of the isolated compounds (1-7) were tested against beta-carotene destruction and LDL oxidation. The isoflavans (1-4) at a concentration of 50 microM inhibited beta-carotene consumption, following 90 min of incubation at 50 degrees C, similar to the inhibitory effect of the whole licorice crude extract (at 16 mg/1). The chalcones (5 and 6) exhibited moderate inhibition and the isoflavone 7 was almost inactive, whereas vitamin E (50 microM) completely inhibited beta-carotene consumption. The inhibitory effect of the constituents 1-7, at a concentration of 30 microM on 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH)-induced LDL oxidation was determined by measuring the amount of the thiobarbituric acid reactive substances (TBARS) and the amount of lipid peroxides. While compounds 1-6 exhibited high inhibitory activity, compound 7 and vitamin E were not active. A dose-dependent inhibitory effect of Glabridin, on the formation of cholesteryl linoleate hydroperoxide (CLOOH), in an AAPH-induced LDL oxidation system was also shown. Glabridin, at 5 or 40-60 microM concentration, inhibited the CLOOH formation by 62% and 90%, respectively. These results suggest that constituents 1-6 are very potent antioxidants toward LDL oxidation with Glabridin being the most abundant and potent antioxidant. As LDL oxidation is a key event in the formation of the early atherosclerotic lesion, the use of these natural antioxidants may be proven beneficial to attenuate atherosclerosis.

Antioxidants↗
PubMed2003

Glabrene and isoliquiritigenin as tyrosinase inhibitors from licorice roots.

Tyrosinase is known to be a key enzyme in melanin biosynthesis, involved in determining the color of mammalian skin and hair. Various dermatological disorders, such as melasama, age spots, and sites of actinic damage, arise from the accumulation of an excessive level of epidermal pigmentation. The inadequacy of current therapies to treat these conditions as well as high cytotoxicity and mutagenicity, poor skin penetration, and low stability of formulations led us to seek new whitening agents to meet the medical requirements for depigmenting agents. The inhibitory effect of licorice extract on tyrosinase activity was higher than that expected from the level of glabridin in the extract. This led us to test for other components that may contribute to this strong inhibitory activity. Results indicated that glabrene and isoliquiritigenin (2',4',4-trihydroxychalcone) in the licorice extract can inhibit both mono- and diphenolase tyrosinase activities. The IC(50) values for glabrene and isoliquiritigenin were 3.5 and 8.1 microM, respectively, when tyrosine was used as substrate. The effects of glabrene and isoliquiritigenin on tyrosinase activity were dose-dependent and correlated to their ability to inhibit melanin formation in melanocytes. This is the first study indicating that glabrene and isoliquiritigenin exert varying degrees of inhibition on tyrosinase-dependent melanin biosynthesis, suggesting that isoflavenes and chalcones may serve as candidates for skin-lightening agents.

Cells, Cultured↗
PubMed2003

Source of arsenic in licorice confectionery products.

Spanish legislation sets a maximum level for total arsenic (As) in confectionery products at 0.1 microg g(-)(1). The U.S. Food and Drug Administration limitations for glycyrrhizic acid in hard and soft candies are 160 and 31 mg g(-)(1), respectively. Arsenic and glycyrrhizic acid were determined in 22 different confectionery products: 9 throat pearls, 4 hard candies, and 9 soft candies. Arsenic and glycyrrhizic acid were quantified by atomic absorption spectrometry with hydride generation and high-performance liquid chromatography, respectively. Levels of glycyrrhizic acid were always below the maximum limits established by the U.S. FDA; however, the As concentration in seven of nine throat pearls (0.55 +/- 0.15 microg g(-)(1)) were above the Spanish maximum limit. A clear empirical relationship between the arsenic and glycyrrhizic acid concentrations was observed (R (2) = 0.9357), implying that to avoid high levels of potentially toxic arsenic in licorice confections high-quality licorice extract should be used.

Arsenic↗
PubMed2005

Isolation and identification of flavonoids in licorice and a study of their inhibitory effects on tyrosinase.

Five different flavonoids were isolated from licorice after multistep chromatographic fractionation. The aim was to identify and characterize active components in licorice responsible for antibrowning activities and to seek new tyrosinase inhibitors for applications as antibrowning and depigmenting agents in the food and cosmetic industries. The isolated flavonoids were identified as liquiritin, licuraside, isoliquiritin, liquiritigenin (from Glycyrrhiza uralensis Fisch.), and licochalcone A (from Glycyrrhiza inflate Bat.) by UV, MS, (1)H NMR, and (13)C NMR analyses. The inhibitory potencies and capacities of these flavonoids toward monophenolase activity of mushroom tyrosinase were investigated. The IC(50) values of licuraside, isoliquiritin, and licochalcone A for monophenolase activity were 0.072, 0.038, and 0.0258 mM, respectively. A study of the mechanisms of monophenolase inhibition by these flavonoids indicated that they are all competitive inhibitors. Different from the above flavonoids, no inhibitory activity was observed for liquiritin, whereas liquiritigenin activated the monophenolase activity as a cofactor. The inhibitory effect of licuraside, isoliquiritin, and licochalcone A on diphenolase activity with l-DOPA as the substrate was much lower than those with l-tyrosine. Results suggest that licuraside, isoliquiritin, and licochalcone A have the high potential to be further developed into effective antibrowning and depigmenting agents.

Agaricales↗
PubMed2005

Licorice compounds glycyrrhizin and 18beta-glycyrrhetinic acid are potent modulators of bile acid-induced cytotoxicity in rat hepatocytes.

The accumulation of hydrophobic bile acids results in cholestatic liver injury by increasing oxidative stress, mitochondrial dysfunction, and activation of cell signaling pathways. Licorice root and its constituents have been utilized as antihepatotoxic agents. The purpose of this study was to evaluate the potential modulation by a primary component of licorice root, glycyrrhizin (GL), and its metabolite, 18beta-glycyrrhetinic acid (GA), in a hepatocyte model of cholestatic liver injury. Preincubation of fresh rat hepatocyte suspensions with GL or GA reduced glycochenodeoxycholic acid (GCDC)-dependent reactive oxygen species generation, with GA more potent than GL. Interestingly, GL and GA had opposing effects toward GCDC-induced cytotoxicity; GA prevented both necrosis and apoptosis, whereas GL enhanced apoptosis. GCDC promoted activation of caspase 10, caspase 3, and PARP; all were inhibited by GA but not GL. Induction of apoptosis by GCDC was also associated with activation of JNK, which was prevented by GA. Activation of caspase 9 and dissipation of mitochondrial membrane potential were prevented by GA but not GL. In liver mitochondrial studies, GL and GA were both potent inhibitors of the mitochondrial permeability transition, reactive oxygen species generation, and cytochrome c release at submicromolar concentrations. Results from this study suggest that GL exhibits pro-apoptotic properties, whereas GA is a potent inhibitor of bile acid-induced apoptosis and necrosis in a manner consistent with its antioxidative effect.

Animals↗