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Birth outcome in relation to licorice consumption during pregnancy.

A role for glucocorticoids is suspected in the etiology of low birth weight. The authors tested whether maternal consumption of glycyrrhizin (an inhibitor of cortisol metabolism) in licorice affects birth weight in humans. A sample of 1,049 Finnish women and their healthy singleton infants was studied in 1998. Glycyrrhizin intake was calculated from detailed questionnaires on licorice consumption. Glycyrrhizin exposure was grouped into three levels: low (<250 mg/week; n = 751), moderate (250-499 mg/week; n = 145), and heavy (> or =500 mg/week; n = 110). Birth weight and gestational age (from ultrasound measurements) were obtained from hospital records. Babies with heavy exposure to glycyrrhizin were not significantly lighter at birth, but they were significantly more likely to be born earlier: The odds ratio for being born before 38 weeks' gestation was 2.5 (95% confidence interval: 1.1, 5.5; p = 0.03). Although the effect of heavy glycyrrhizin intake on mean duration of gestation was small (2.52 days) when expressed as an effect on the mean, this shift to the left of the distribution of duration of gestation was sufficient to double the risk of being born before 38 weeks. The association remained in multivariate analyses. In conclusion, heavy glycyrrhizin exposure during pregnancy did not significantly affect birth weight or maternal blood pressure, but it was significantly associated with lower gestational age.

Adult↗

Preterm birth and licorice consumption during pregnancy.

Heavy licorice (glycyrrhizin) consumption has been associated with shorter gestation. The aim of the present study was to test whether this association also applies to preterm (<37 weeks) births. In 2000-2001, a sample of 95 Finnish women who delivered preterm singletons was compared with controls (n = 107) who delivered babies of normal gestational age in the same hospital. Glycyrrhizin intake was calculated from questionnaires containing detailed items on licorice consumption. Glycyrrhizin exposure was grouped into three levels: low (<250 mg/week), moderate (250-499 mg/week), and heavy (> or =500 mg/week). Heavy consumption versus a lower level of consumption was associated with a more than twofold increased risk of preterm (<37 weeks) delivery. The association was stronger when only the 40 births classified as early preterm delivery (<34 weeks) were included (odds ratio = 3.07, 95% confidence interval: 1.17, 8.05 for the fully adjusted model). In conclusion, heavy glycyrrhizin exposure was associated with preterm delivery and may be a novel marker of this condition.

Adult↗

Free radicals in licorice-flavored sweets can Be detected noninvasively using low frequency electron paramagnetic resonance after oral administration to mice.

The observation of the fate of free radicals coming from food after oral administration could be important in evaluating their reactivity in vivo. The aim of this study was to demonstrate that it is feasible to detect directly in vivo free radicals coming from food with the use of low frequency electron paramagnetic resonance (EPR) spectroscopy. Because polyphenols are easily oxidized into stable radicals, we assumed that these radicals could be detected in food. We chose licorice, which contains several types of polyphenols. The presence of free radicals was demonstrated in licorice-flavored sweets. Using low frequency EPR spectroscopy, we detected these free radicals directly and noninvasively after oral administration to mice. These radicals were rather stable in the guts of the mice. This study is the first report demonstrating noninvasively the presence of free radicals in vivo coming from food.

Administration, Oral↗

CYP3A4 inhibitors isolated from Licorice.

The extract of licorice (Glycyrrhiza uralensis FISHER, Leguminosae) showed CYP3A4 inhibitory activity with the IC50 value of 0.022 mg/ml. Bioassay-guided purification afforded nine compounds, 3-(p-hydroxyphenyl)propionic acid (1), isoliquiritigenin (2), (3R)-vestitol (3), licopyranocoumarin (4), 4-hydroxyguaiacol apioglucoside (5), liquiritin (6), liquiritigenin 7,4'-diglucoside (7), liquiritin apioside (8), and glucoliquiritin apioside (9). Among these compounds, 3, 7, and 5 showed potent CYP3A4 inhibitory activities with IC50 values of 3.6, 17, and 20 microM, respectively. Glycyrrhizin (10), a main constituent of licorice, however, was inactive for CYP3A4 inhibition.

Cytochrome P-450 CYP3A Inhibitors↗

Inhibition of adenosine 3',5'-cyclic monophosphate phosphodiesterase by flavonoids from licorice roots and 4-arylcoumarins.

Isoliquiritigenin, glabridin, licoarylcoumarin and licoricidin were identified as strong inhibitors of adenosine 3',5'-cyclic monophosphate (cAMP) phosphodiesterase in waste materials which were obtained during the industrial extraction of glycyrrhizin from licorice roots. The structure-activity relationships of 12 flavonoids from licorice roots and 34 4-arylcoumarins were studied. In 4-arylcoumarins, 5,7-dihydroxy derivatives were generally highly inhibitory towards cAMP phosphodiesterase.

3',5'-Cyclic-AMP Phosphodiesterases↗

[Properties of glycyrrhizin in Kampo extracts including licorice root and changes in the blood concentration of glycyrrhetic acid after oral administration of Kampo extracts].

We investigated in vitro the properties of glycyrrhizin (GL), such as dissolution, absorption and resolution, using a Sho-Seiryu-To extract, a Sho-Saiko-To extract, both including a licorice root, and licorice extract. The dissolution of GL differed with the pH of the solvent. The absorption (partition coefficient) of GL decreased with an increase in pH, and increased in the presence of other active constituents, such as baicalin, baicalein, and ephedrine. In the case of the Sho-Saiko-To extract, the conversion from GL to glycyrrhetic acid (GA) by beta-glucuronidase originated from E. coli occurred slowly. It was also suppressed by adding baicalin. We determined in vivo the pharmacokinetics of GA after oral administration of Kampo extracts in healthy volunteers. In each Kampo extract, the time of administration had no influence on the mean maximum blood concentration (Cmax) and the area under the blood concentration-time curve (AUC). Tmax was delayed in the case of the administration after meal (p < 0.05).

Administration, Oral↗

[Quantitative determination of constituents in various licorice roots by means of high performance liquid chromatography].

During the course of our studies on the chemical constituents of botanically identified Chinese licorice roots of various origins, we have identified 15 kinds of saponins and 49 kinds of flavonoids (including flavonoid glycosides). With these chemical constituents at hand, we have carried out the chemical evaluation studies of licorice roots available in Japan by means of high performance liquid chromatography (HPLC). In the HPLC analysis using an ODS reversed-phase column, a combination of 1% aqueous acetic acid and acetonitrile was used as the mobile phase in a gradient solvent system, and the eluate was monitored with UV absorption at 254 nm (for saponins with a diene or a conjugated carbonyl moiety, liquiritin, and liquiritin apioside) or at 350 nm (for other flavonoid constituents). By our analytical method described here, quantitative analyses of saponin and flavonoid constituents were effected simultaneously. We have found an interesting piece of information concerning the origin of parent plants and their characteristic constituents such as saponins and flavonoids.

Chromatography, High Pressure Liquid↗

Determination of low levels of methanol and ethanol in licorice extract by large volume injection head-space GC.

A large volume injection head-space GC method was established for measuring low levels of residual methanol and ethanol in licorice extract used a food additive. A vial was kept at 50 degrees C in the oven of the head-space sampler. Injection of the head-space gas for 0.75 min into a Poraplot Q GC column with a initial oven temperature of 35 degrees C, enabled the determination of low levels (5 micrograms/g) of methanol and ethanol. The standard deviations for five rounds of analysis of methanol and ethanol in licorice extracts were between 0.82 and 2.97. Methanol was found in 6 samples out of 9 collected in 1999, at concentrations exceeding 50 micrograms/g, the limit set by the Japanese Government, established in 1999 and coming into force on April 1, 2000. The highest concentration reached 10,000 micrograms/g. Methanol at a concentration exceeding 50 micrograms/g was found in 2 out of 9 samples collected in 2000. The highest concentration was 270 micrograms/g.

Chromatography, Gas↗

Licorice-induced pseudoaldosteronism.

Licorice ingestion as a cause of pseudoaldosteronism is discussed. The mechanism whereby licorice, when consumed in large quantities, exhibits the physiologic properties of aldosterone, is reviewed. A case report of a 51-year-old male hospitalized with hypertension and hypokalemia is presented with reports of laboratory findings which lead to the diagnosis of pseudoaldosteronism.

Glycyrrhiza↗

[Advances in studies on flavonoids of licorice].

The progress in the research of the active ingredients of licorice flavonoid and the pharmacological activities was reviewed. Licorice flavonoid constituents mainly included flavones, flavonals, isoflavones, chalcones, bihydroflavones and bihydrochalcones. Pharmacological investigation concluded that they had antioxidant, antibacterial, antitumer and inhibiting HIV activities. It is important to study further the flavonoid constituents and pharmacological activities.

Animals↗

[Licorice of 'shakuyaku kanzou tou' induced pseudoaldosteronism].

We report a case of pseudoaldosteronism induced by licorice in a kampo medication 'Shakuyaku Kanzou Tou' that was diagnosed after relief of urinary retention due to benign prostatic hypertrophy (BPH). A-71-year-old man was admitted to our hospital due to urinary retention. At admission, he had hypertension and leg edema, but serum potassium was in the normal range. One day after admission, hypokalemia was recognized. He was taking "Shakuyaku Kanzou Tou", a Chinese medicine that contains glycyrrhizin. So we suspected pseudoaldosteronism and had him stop taking it. Computed tomography did not reveal any adrenal tumor. Plasma rennin activity and aldosterone level were suppressed. Gradually, hypertension and leg edema improved and serum potassium became within the normal range. We diagnosed the case as pseudoaldosteronism induced by licorice of 'Shakuyaku Kanzou Tou'. Since we suspected BPH to be the cause of urinary retention, we performed transurethral resection of prostate. After surgery, he was able to void smoothly.

Aged↗

[Effect of HKL-4 on active oxygen metabolism and photochemical efficiency in licorice leaf].

OBJECTIVE: To study the effects of HKL-4 on physiological changes during growth of leaves. METHOD: Using licorice (Glycyrrhiza uralensis) as material, the effects of HKL-4 on active oxygen metabolism and photochemical efficiency in licorice leaf were determined under field condition. RESULT AND CONCLUSION: The contents of chlorophyll, activity of SOD and CAT increased, while the MDA contents in leaves decreased. The senescence was delayed, so that the photochemical efficiency (Fv/Fm) was increasing comparing to the control.

Catalase↗

[Quality evaluation of Chinese licorice].

The contents of 12 compounds, viz. glycyrrhizinic acid, uralsaponin A, uralsaponin B, liquiritin, isoliquiritin, liquiritigenin, isoliquiritigenin, glycycoumarin, isoglycycoumarin, licochalcone A, glycyrol and isoglycyrol, present in Chinese licorice, the roots and rhizomes of 8 Glycyrrhiza species collected from 15 districts in China, were determined by high performance liquid chromatographic method. The quality evaluation of Chinese licorice was discussed according to the results of the determinations.

Chromatography, High Pressure Liquid↗

[Separation and quantitative determination of three saponins in licorice root by high performance liquid chromatography].

A new analytical method for the separation and simultaneous determination of three saponins in Licorice root by high performance liquid chromatography has been developed. The saponins, glycyrrhizic acid (S-I), uralsaponin B (S-II) and uralsaponin A (S-III) were separated and determined by use of the solvent system CH3CN-3% HOAc (H2O) (47:53) at 248 nm, and with gradient increasing flow rate, the operation can be completed in 20 min. This method is sensitive and acuate with good reproducibility. The contents of three saponins in Chinese Licorice roots derived from four Glycyrrhiza species were determined.

Anti-Infective Agents↗

[Arterial hypertension caused by ingestion of licorice].

The Authors present a case of licorice-sustained hypertension in a young man. blood and urine tests revealed: hypokaliemia with hyperkaliuria, suppressed plasmatic renin activity, absent urinary aldosterone. A symmetric left ventricular hypertrophy was detectable at the echocardiogram. Five months after the interruption of licorice ingestion the valves of systemic blood pressure were normal and the haematochemical investigations were also within normal limits. An echocardiogram revealed the disappearance of the signs of left ventricular hypertrophy and myocardial mass was reduced of about 40%. The usefulness of an echocardiographic examination, to evaluate hypertensive cardiomyopathy, is stressed.

Adult↗

[Licorice-induced myopathy. Report of a new case].

A 64 year-old man, who had been ingesting 20 g of licorice daily for about five months, developed a progressive, diffuse muscle weakness, with myoglobinuria, severe hypokalemia and elevated serum muscle enzymes. Electromyography and muscle biopsy results were consistent with a necrotizing myopathy. Following licorice withdrawal and appropriate electrolyte administration, complete clinical recovery was observed within about ten days. Previous reports of similar cases are reviewed and causative factors of this kind of myopathy are discussed.

Foodborne Diseases↗

Licorice-induced hypokalemic myopathy and hypokalemic renal tubular damage in anorexia nervosa.

A patient with a history of anorexia nervosa developed licorice-induced hypokalemic myopathy. With potassium replacement, high CPK blood level and myopathic signs returned to normal. However, the patient manifested persistent hypokalemia and impaired renal function to concentrate and acidify the urine. Renal biopsy demonstrated intense degeneration and vacuolation of tubules with a normal glomerus which was consistent with hypokalemic nephropathy. Prolonged hypokalemia in anorexia nervosa is sometimes attributed to surreptitious purging or taking diuretics, but it is necessary to check the urine pH, the urine-specific gravity, and the urine potassium level in order to find underlying renal damage even after hypokalemic myopathy is treated successfully.

Adult↗

CYP81E1, a cytochrome P450 cDNA of licorice (Glycyrrhiza echinata L.), encodes isoflavone 2'-hydroxylase.

The microsome of yeast cells overexpressing CYP81E1, a cytochrome P450 cDNA recently cloned from licorice (Glycyrrhiza echinata L., Fabaceae), catalyzed the hydroxylation of isoflavones, daidzein and formononetin, to yield 2'-hydroxyisoflavones, 2'-hydroxydaidzein, and 2'-hydroxyformononetin, respectively. The chemical structures of the reaction products were confirmed by mass spectrometric analysis. Genistein also yielded a putative 2'-hydroxylated product, but flavanones and cinnamic acid derivatives were not used as substrates for the reaction with the recombinant yeast microsome. CYP81E1 protein was thus demonstrated for the first time to be isoflavone 2'-hydroxylase involved in the biosynthesis of isoflavonoid-derived antimicrobial compounds of legumes.

Cloning, Molecular↗