Licorice Root Extract Research Articles

Modulation of lipopolysaccharide-induced pro-inflammatory mediators by an extract of Glycyrrhiza glabra and its phytoconstituents

To evaluate the inhibitory property of de-glycyrrhizinated extract of Glycyrrhiza glabra root and its phytoconstituents (glabridin, isoliquiritigenin and glycyrrhizin) on LPS-induced production of pro-inflammatory mediators. Inhibitory effect of G. glabra extract and its phytoconstituents were studied on lipopolysaccharide (LPS)-induced nitric oxide (NO), interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) levels in J774A.1 murine macrophages. G. glabra and isoliquiritigenin significantly inhibited LPS stimulated NO, IL-1 beta and IL-6 production. Glabridin showed significant inhibition of NO and IL-1 beta release, but failed to attenuate IL-6 levels at the tested concentrations. In addition, glycyrrhizin did not exhibit inhibitory response towards any of the LPS-induced pro-inflammatory mediators at the tested concentrations. From the results we speculate that the inhibitory effect of G. glabra extract on LPS-induced pro-inflammatory mediators is influenced by glabridin and isoliquiritigenin and is not contributed by glycyrrhizin.

Ginseng (Panax quinquefolius) and Licorice (Glycyrrhiza uralensis) Root Extract Combinations Increase Hepatocarcinoma Cell (Hep‐G2) Viability

The combined cytoactive effects of American ginseng (Panax quinquefolius) and licorice (Glycyrrhiza uralensis) root extracts were investigated in a hepatocarcinoma cell line (Hep-G2). An isobolographic analysis was utilized to express the possibility of synergistic, additive or antagonistic interaction between the two extracts. Both ginseng and licorice roots are widely utilized in traditional Chinese medicine preparations to treat a variety of ailments. However, the effect of the herbs in combination is currently unknown in cultured Hep-G2 cells. Ginseng (GE) and licorice (LE) extracts were both able to reduce cell viability. The LC50 values, after 72 h, were found to be 0.64 ± 0.02 mg/mL (GE) and 0.53 ± 0.02 mg/mL (LE). An isobologram was plotted, which included five theoretical LC50s calculated, based on the fixed fraction method of combination ginseng to licorice extracts to establish a line of additivity. All combinations of GE to LE (1/5, 1/3, 1/2, 2/3, 4/5) produced an effect on Hep-G2 cell viability but they were all found to be antagonistic. The LC50 of fractions 1/3, 1/2, 2/3 were 23%, 21% and 18% above the theoretical LC50. Lactate dehydrogenase release indicated that as the proportion of GE to LE increased beyond 50%, the influence on membrane permeability increased. Cell-cycle analysis showed a slight but significant arrest at the G1 phase of cell cycle for LE. Both GE and LE reduced Hep-G2 viability independently; however, the combinations of both extracts were found to have an antagonistic effect on cell viability and increased cultured Hep-G2 survival.

Protective Effects of Glycyrrhizin against .BETA.2-Adrenergic Receptor Agonist-Induced Receptor Internalization and Cell Apoptosis

It has been reported that treatment with β₂ adrenergic receptor (β₂AR) agonist bronchodilators may result in airway β₂ARs internalization and cardiac muscle cells apoptosis. This could lead to the loss of pharmacological effect of β₂AR agonists and increase adverse cardiovascular events in asthma patients receiving β₂AR agonist therapy. Glycyrrhizin, the major bioactive component of licorice root extract, has been reported to exhibit protective effect on respiratory system. Here, we investigate the effects of glycyrrhizin against β₂AR agonist salbutamol-induced receptor internalization and cell apoptosis. In our study, the live cell confocal imaging and fixed-cell enzyme-linked immunosorbent assay (ELISA) assay revealed that glycyrrhizin significantly inhibited salbutamol-induced surface β₂AR internalization. The underlying mechanisms were then identified to be that glycyrrhizin could reduce the association of β₂ARs with β-arrestins and clathrin heavy chain as well as the level of G protein-coupled receptor kinase (GRK) mediated phosphorylation of β₂ARs. The inhibition of receptor internalization by glycyrrhizin further lead to stabilization of the β₂AR mRNA and protein expression, thus amplified the transmembrane signaling via the β₂ARs. We also proved that glycyrrhizin could profoundly attenuate salbutamol-induced early cellular apoptosis by regulating the expressions of B-cell lymphoma 2 (Bcl-2) family genes. Taken together, our results suggest that glycyrrhizin exhibits protective effects against β₂AR agonist-induced receptor internalization and cell apoptosis. These findings might have practical implications for future strategies of combined application of glycyrrhizin with β₂AR receptor agonists to improve the efficacy of bronchodilators in patients with asthma and chronic obstructive pulmonary disease (COPD).

Clinical reduction of S. mutans in pre-school children using a novel liquorice root extract lollipop: a pilot study

To determine the clinical effect of a simple herbal caries-prevention protocol aimed at reduction of Streptococcus mutans (SM) in young children in a pre-school setting. Proof-of-principle pilot study. To prove the concept this pilot study delivered a clinical intervention using sugar-free lollipops containing liquorice root extract. Regimen: Supervised herbal lollipops, twice daily for 3 weeks. Species-specific monoclonal antibody testing of saliva provided SM counts. Children were grouped in high, medium and low caries-risk using baseline SM-levels as risk-indicator. Bacterial numbers at baseline, during intervention, and for 9 weeks post-intervention were compared. SM levels were analysed using GEE modelling. High-risk children showed the steepest early decrease in mean log-SM (P<.001). At end of a follow-up period, the log-SM decrease moved the high-risk group down to moderate-risk level. High-risk children showed a decrease in fitted mean SM% not seen in other groups (P<.001). The decrease reached a nadir around 22-days post-intervention. Twice-daily use of herbal lollipop significantly reduced both number and relative percent of SM in high-risk children. SM numbers were reduced for 22 days after the last lollipop, stabilized and then began to rebound. A potential for simple effective caries-prevention for high-risk children has been demonstrated. Encouraging results warrant randomised clinical trials (RCT) of liquorice root in herbal lollipops or alternative modes of delivery.

Synthesis of glycyrrhetinic acid by hydrolysis of licorice root extract in subcritical water

A procedure for the synthesis of glycyrrhetinic acid (glycyrrhyzic acid aglicone) by hydrolysis of licorice root extract in subcritical water was developed. The procedure was shown to be more effective than conventional hydrolysis. Glycyrrhetinic acid was identified and its concentration in the product determined by high-performance liquid chromatography. A 13C NMR spectroscopic study confirmed that glycyrrhetinic acid obtained in subcritical water had a β configuration at the C18 atom.

18β-Glycyrrhetinic acid inhibits periodontitis via glucocorticoid-independent nuclear factor-κB inactivation in interleukin-10-deficient mice

18β-Glycyrrhetinic acid (GA) is a natural anti-inflammatory compound derived from licorice root extract (Glycyrrhiza glabra). The effect of GA on experimental periodontitis and its mechanism of action were determined in the present study. Periodontitis was induced by oral infection with Porphyromonas gingivalis W83 in interleukin-10-deficient mice. The effect of GA, which was delivered by subcutaneous injections in either prophylactic or therapeutic regimens, on alveolar bone loss and gingival gene expressions was determined on day 42 after initial infection. The effect of GA on lipopolysaccharide (LPS)-stimulated macrophages, T cell proliferation and osteoclastogenesis was also examined in vitro. 18β-Glycyrrhetinic acid administered either prophylactically or therapeutically resulted in a dramatic reduction of infection-induced bone loss in interleukin-10-deficient mice, which are highly disease susceptible. Although GA has been reported to exert its anti-inflammatory activity via downregulation of 11β-hydroxysteroid dehydrogenase-2 (HSD2), which converts active glucocorticoids to their inactive forms, GA did not reduce HSD2 gene expression in gingival tissue. Rather, in glucocorticoid-free conditions, GA potently inhibited LPS-stimulated proinflammatory cytokine production and RANKL-stimulated osteoclastogenesis, both of which are dependent on nuclear factor-κB. Furthermore, GA suppressed LPS- and RANKL-stimulated phosphorylation of nuclear factor-κB p105 in vitro. These findings indicate that GA inhibits periodontitis by inactivation of nuclear factor-κB in an interleukin-10- and glucocorticoid-independent fashion.

Leucoderma after use of a skin-lightening cream containing kojic dipalmitate, liquorice root extract andMitracarpus scaberextract

A lighter or whiter complexion is socially desirable in many cultures. This has led to an unregulated and highly profitable market in skin-lightening creams that are readily available over the counter or on the internet. Plant extracts and newer tyrosinase inhibitors such as kojic acid or its derivative kojic dipalmitate are popular ingredients in these creams. We report a patient who developed depigmented patches after using such a cream.

EFFECT OF FOLIAR SPRAY OF ZINC AND lIQUORICE ROOT EXTRACT ON SOME VEGETATIVE AND FLOWERING GROWTH PARAMETERS OF TWO STRAWBERRY VARIETIES (Fragaria x ananassa Duch.)

This research conducted during the growing season, 2006/ 2007 at the department of Horticulture and landscape design, college of Agriculture and forestry, Mosul university, IRAQ. The goals of this study was to investigate the effect of three concentrations of zinc element (0, 50 and 100 mg zn/L) and three concentration of liquorice root extract (0, 2 and 4gm/L) used as a foliar spray on vegetative and flowering parameters of two strawberry varieties (Hapil and Kaiser's samlling). A spilt-split plot within RCBD design with three replicates (each include 12 plants) was applied in this research . All data were teasted by using Duncan's multiple range teast under 5% level. Results obtained indicated that, Hapil variety significantly overtopped in average single leaf area, number of rooted stolensو total chlorophyll content and percentage of flowers set, while kaiser's samilng variety significantly superior in both number of crowns and flower's per plant. Spraying of 100 mg/L of zinc caused a significant increase in both number of crowns and flowers per plant. At the same time, the second conc. of liquorices (2 gm/L) gave a significant increase in average leaf area and foliage dry weight, but the third conc. (4gm/L) of liquorices caused a significant increase in both number of stolen and flowers per plant and total chlorophyll content.An additional increases were noticed in some vegetative and flowering parameters in both strawberry varieties by applying both bi or third interaction treatments.

Abstract 1445: Growth inhibitory and anti-metastatic effects of the hexane/ethanol extract of Glycyrrhiza uralensis in a mouse breast cancer xenograft model

Abstract Glycyrrhiza uralensis (licorice) is one of the most frequently prescribed ingredients in Oriental medicine and licorice root extracts have previously been shown to exhibit anti-carcinogenic activities. However, these extracts harbor considerable quantities of glycyrrhizin, which is known to exert anticarcinogenic activities and to induce severe hypokalemia and hypertension. In this study, we evaluated the effects of the hexane/ethanol extract of Glycyrrhiza uralensis (HEGU), which lacks glycyrrhizin, on the metastatic characteristics of 4T1 murine mammary carcinoma cells. When 4T1 cells were cultured on a transwell-filter in an in vitro cell culture model, HEGU inhibited cell migration and adhesion in a dose-dependent manner. Gelatin zymography and Western blot analysis showed that HEGU significantly suppressed the secretion and activation of the matrix metalloproteinase (MMP)-2 and MMP-9. The secretion of tissue inhibitor of metalloproteinase (TIMP)-1 was reduced in HEGU-treated cells. HEGU reduced the protein levels of intercellular adhesion molecule and vascular cell adhesion molecule. To assess the effects of HEGU on lung metastasis in vivo, we injected 4T1 cells (5×104 cells) into the inguinal mammary fat pads of syngeneic, immunocompetent BALB/c mice. One week after 4T1 cell injection, the mice were given HEGU (5 mg/kg body weight/day) in the drinking water for 25 days. HEGU treatment inhibited the solid tumor growth and the number of pulmonary tumor nodules. Immunohistochemistry results revealed that HEGU treatment reduced the expression of CD31, vascular endothelial growth factor (VEGF), proliferating cell nuclear antigen and cyclin-dependent kinase 4 in the tumor tissues. In addition, the serum concentrations of MMP-9 and VEGF were decreased in the sera of mice treated with HEGU. In the present study, we have demonstrated in both in vivo and in vitro systems that HEGU greatly inhibits the growth and lung metastasis of 4T1 cells, which was accompanied by reduced levels of MMPs, adhesion molecules and VEGF. These data suggest that HEGU possesses chemotherapeutic efficacy against breast cancer including the growth of tumor and inhibition of metastasis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1445.

Effects of licorice root extract on the number of nocturnal hot flashes in menopausal women

Background and aimMenopause entails many complications on women’s quality of life. Hot flashes is the most common and bothersome effect, mainly treated with hormonal therapy. However, because of its side effects, there is controversy over its administration. Thus, therapies with fewer complications such as herbs warrant investigation. The aim of this randomized double-blind clinical trial was to determine the effects of licorice root extract on the number of nocturnal hot flashes in menopausal women referring to healthcare centers affiliated to Shahid Beheshti University of Medical Sciences in 2008. Materials and methods68 women were selected with purposive sampling method and randomly divided into 2 equal experimental and placebo groups. After taking their consent, data were gathered with a questionnaire and information forms validated through content method. Reliability was ensured by using standard brands for meter band, weights, stethoscope and sphygmomanometer calibrated according to guidelines of manufacturers. Both experimental and placebo groups took capsules containing 330 mg licorice and starch 3 times a day (morning, noon and night) over 4 weeks respectively. The numbers of nocturnal hot flashes were measured from 2 weeks before the intervention to the end of it. Data were analyzed by SPSS 11.5. FindingsMeans of age, duration of amenorrhea and duration of hot flashes were 53.13, 1.65 and 1.65 respectively. The numbers of hot flashes in the experimental group were 4.82 before the intervention and 1.05 after it with a significant difference. However, no significant difference was found before and after the intervention in the placebo group. ConclusionLicorice as an herb may decrease the number of nocturnal hot flashes in menopausal women, increasing their physical and psychological health. Keywords: Hot flashes, Menopause, Licorice. *Corresponding Author: Fatemeh Nahidi. Lecturer, Dept. of Midwifery, Faculty of Nursing and Midwifery, Shahid Beheshti University of Medical Sciences, Tehran, Iran. E-mail: nahidifateme@yahoo.com

Suppression of liver injury through inhibition of MyD88 signaling in a mouse model of fulminant hepatitis by 18β-glycyrrhetinic acid (142.11)

Abstract Fulminant hepatitis, develops secondary to infection, toxin or immune mediated attack, is a rare but potentially fatal disease. However, the molecular mechanisms underlying are not well known. 18β-glycyrrhetinic acid (GA), the major bioactive component of licorice root extract, has a protective effect on hepatic injury and exhibits anti-inflammatory activity. Here we investigate the potential role of GA in a mouse model of fulminant hepatitis induced by injection of Propionibacterium acnes (P. acnes) and LPS. GA or vehicle control was administered intraperitoneally daily 1 d after P. acnes priming. The results revealed that GA treatment significantly improved mouse mortality and ameliorated liver injury through inhibition of the activation and proliferation of liver-infiltrating CD4+ T cells and the production of serum pro-inflammatory cytokines such as IFN-γ and TNF-α. However, GA exhibited no direct effect on the proliferation of liver-infiltrating CD4+ T cells, but by reduced recruitment of CD11c+B220- DC precursors into the liver, which is mediated by the inhibition of MIP-1α expression in Kupffer cells by GA. More importantly, GA inhibited the activation of Kupffer cells by down-regulating MyD88 expression and its down-stream signal NF-κB activation. Taken together, our results suggest that GA exhibits anti-inflammatory effects through inhibition of MyD88 signaling in a mouse model of fulminant hepatitis.

18β-Glycyrrhetinic Acid Ameliorates Acute Propionibacterium acnes-induced Liver Injury through Inhibition of Macrophage Inflammatory Protein-1α

18Beta-glycyrrhetinic acid (GA), the major bioactive component of licorice root extract, has a protective effect on hepatic injury and exhibits antiinflammatory activity. Here, we investigate the effect of GA in Propionibacterium acnes-induced acute inflammatory liver injury. C57BL/6 mice were primed with P. acnes followed by lipopolysaccharide challenge to induce fulminant hepatitis. GA (75 mg/kg) or vehicle control was administered intraperitoneally daily 1 day after P. acnes priming, and GA significantly improved mouse mortality. Then, to investigate the underlying mechanisms of GA in this acute inflammatory liver injury model, we primed C57BL/6 mice with P. acnes only. We propose that GA ameliorates acute P. acnes-induced liver injury through reduced macrophage inflammatory protein (MIP)-1alpha expression in Kupffer cells by down-regulating MyD88 expression and inhibiting NF-kappaB activation. Reduced MIP-1alpha expression lowered the recruitment of CD11c(+)B220(-) dendritic cell precursors into the liver. Consequently, GA treatment inhibits the activation and proliferation of liver-infiltrating CD4(+) T cells and reduces the production of serum alanine aminotransferase and proinflammatory cytokines such as interferon-gamma and tumor necrosis factor-alpha. Moreover, anti-MIP-1alpha treatment in P. acnes-primed mice inhibits the recruitment of dendritic cell precursors into the liver and suppresses mouse mortality as GA does. Taken together, our results suggest that GA exhibits antiinflammatory effects through inhibition of MIP-1alpha in a mouse model of acute P. acnes-induced inflammatory liver injury.

Antiviral effect of diammonium glycyrrhizinate and lithium chloride on cell infection by pseudorabies herpesvirus

Diammonium glycyrrhizin (DG), a salt from glycyrrhizinate (GL) that is a major active component of licorice root extract with various pharmacological activities was investigated for its inhibitory effect on pseudorabies virus (PrV) infection. In parallel, lithium chloride (LiCl), a chemical reagent with potential antiviral activity was compared with DG for their inhibitory ability against PrV infection in vitro. Virus plaque-reduction assays, PCR and RT-PCR analysis indicated that both drugs inhibited cell infection by PrV. Moreover, addition of the drugs resulted in fewer apoptotic cells during PrV infection.

중탄산소듐 용액에서 납의 부식방지제인 자연산물질들

0.1 M 중탄산소듐 용액에서 납전극부식에 대한 로소니아, 감초뿌리 및 카로브 추출물수용액의 부식방지작용에 대한것을 정전류극성방법을 사용해 연구하였다. 이들 물질들의 부식방지작용을 지적해주는 것으로 이들 물질들이 존재할 때 부식속도가 감소하는 것이 발견되었다. 부식방지효율은 추출물농도가 증가하면 증가한다. 이들 추출물의 부식방지작용은 납표면에 이들 추출물이 흡착되어 물질 및 하전이동의 장벽을 만들어 나타내는 것으로 설명되었다. 이들 추출물의 납표면에 흡착은 자발적으로 일어나며, Freundlich 등온흡착을 따르는 것으로 발견되었다. 또한, 변전위양극분극법을 사용해 이들 추출물은 염소를 포함한 용액에서 납의 움푹패이게 하는 부식으로부터 잘 보호해주는 것이 발견되었다. The inhibitive action of the aqueous extract of lawsonia, licorice root and carob toward the corrosion of tin electrode in 0.1 M <TEX>$NaHCO_3$</TEX> solutions was investigated using galvanostatic polarization measurements. It was found that the corrosion rate decreases in the presence of these extracts indicating the inhibiting of these compounds. The inhibition efficiency increases with increasing extract concentration. The inhibition action of these extracts was explained in view of adsorption of its compounds onto the tin surface, making a barrier to mass and charge transfer. The adsorption of these extracts on the tin surface was found to be a spontaneous process and follow Freundlich adsorption isotherm. It is also found that these extracts provide a good protection to tin against pitting corrosion in chloride containing solution using potentiodynamic anodic polarization technique.

A rapid screening method for prenylated flavonoids with ultra‐high‐performance liquid chromatography/electrospray ionisation mass spectrometry in licorice root extracts

Due to their substitution with an isoprenoid group, prenylated flavonoids have an increased affinity for biological membranes and target proteins, enhancing their potential bioactivity. Although many prenylated flavonoids have been described, there are no methods that specifically screen for their presence in complex mixtures, prior to purification. We describe a method based on ultra-high-performance liquid chromatography (UHPLC) with electrospray ionisation mass spectrometry (ESI-MS) that allows rapid screening for prenylated flavonoids in multi-component plant extracts. Identification of the prenylated flavonoids is based on screening for neutral losses of 42 u and 56 u in the positive-ion mode MS(2) and MS(3) spectra within the MS chromatograms. In addition, this method discriminates between a prenyl chain and a ring-closed prenyl (pyran ring), based on the ratio of the relative abundances of the ions that lose 42 u and 56 u (42:56). The application of this screening method on a 70% aq. ethanol, ethanol and ethyl acetate extract of the roots of Glycyrrhiza glabra indicated the presence of 70 mono- and di-prenylated flavonoids. In addition, of each prenylated flavonoid the type of prenylation, chain or pyran ring was determined.

Synthesis of new hetero- and carbocyclic aromatic amides of glycyrrhizic acid as potential anti-HIV agents

Members of a new group of di- and trisubstituted amides of glycyrrhizic acid (GA), the major component of licorice root extract, were synthesized; derivatives contained fragments of heterocyclic and aromatic amines (2-aminopyridine, 4-aminopyridine, 5-aminouracil, sulfadimezine, sulfapyridazine, and L-histidine methyl ester) using the dicyclohexylcarbodiimide method. Amides of GA containing 2-aminopyridine and 5-aminopurine residues had anti-HIV-1 activity in MT-4 cell cultures. The index of selectivity (IS) of the amide of GA with 5-aminouracil was, using various parameters, from 27.73 to 277.32, exceeding values for GA (from 4.45 to 24.0).

Estrogenic activities of extracts of Chinese licorice ( Glycyrrhiza uralensis) root in MCF-7 breast cancer cells

Despite the wide use of Chinese licorice root ( Glycyrrhiza uralensis) for the treatment of menopausal complaints, little is known on its potential estrogenic properties, and available information relative to its effects on cell proliferation is contradictory. In this study, the estrogenic properties of licorice root were evaluated in vitro by use of several assays. The effects of increasing concentrations of a DMSO extract of licorice root on the growth of MCF-7 breast cancer cells were biphasic. The extract showed an ER-dependent growth-promoting effect at low concentrations and an ER-independent anti-proliferative activity at high concentrations. In further experiments, licorice root was sequentially extracted to yield four fractions: hexane, EtOAc, methanol and H 2O. Only the EtOAc extract had effects on cell proliferation similar to the DMSO extract. The hexane extract had no effect on cell growth. In contrast, the methanol and water extracts showed an ER-independent, growth-promoting effect. Similar to its effects on cell proliferation, the EtOAc extract had a biphasic effect on S phase cell cycle distribution and the level of PCNA protein. This extract-induced transactivation of endogenous ERα in MCF-7 cells, supported by inducing down-regulation of ERα protein and mRNA levels, and up-regulation of ERα target genes pS2 and GREB1. These results suggest that the activity of licorice root and the balance between increased risk for cancer and prevention of estrogen-dependent breast cancer may depend on the amount of dietary intake.

Evaluation of antioxidant and anti-atherogenic properties of Glycyrrhiza glabra root using in vitro models

The aim of present study was to evaluate antioxidant property of Glycyrrhiza glabra root extracts using in vitro models. The dose-dependent aqueous and ethanolic extracts demonstrated the scavenging activity against nitric oxide (concentration that caused 50% inhibition of nitric oxide radicals [IC50]=72 and 62.1 µg/ml, respectively), superoxide (IC50=64.2 and 38.4 µg/ml, respectively), hydroxyl (IC50=81.9 and 63 µg/ml, respectively), DPPH (IC50=43.6 and 28.3 µg/ml, respectively) and ABTS•+ (IC50=77.3 and 57.2 µg/ml, respectively) radicals. Further, both extracts showed strong reducing power and iron-chelating capacities. In the Fe2+/ascorbate system, both extracts were found to inhibit mitochondrial fraction lipid peroxidation. In copper-catalyzed human serum and low-density lipoprotein oxidation models, both extracts significantly (P<0.05) lengthened the lag phase along with a decline in the oxidation rate, conjugated dienes, lipid hydroperoxides and thiobarbituric acid reactive substance formation. In conclusion, ethanolic extract of G. glabra possess considerable antioxidant activity and protective effect against the human lipoprotein oxidative system.

The Disposition of Diammonium Glycyrrhizinate and Glycyrrhetinic Acid in the Isolated Perfused Rat Intestine and Liver

The major component of liquorice root extract, glycyrrhizinate (GZ), has been formulated as an injection for the treatment of hepatitis. If given orally, GZ has poor bioavailability and is catalysed to glycyrrhetinic acid (GA) by intestinal bacteria. GA is subsequently responsible for significant side effects. This study was conducted to clarify the relationship between GZ and GA absorption and bioavailability. GZ and GA absorption were investigated using the in situ single pass isolated perfused intestine (IPI). Hepatic disposition was investigated using isolated perfused liver (IPL) and in vivo biliary excretion models. The apparent permeability and absorption rate constants in the IPI for GZ were 0.36 +/- 0.31 cm/min and 0.35 +/- 0.33 min (-1), while those for GA were 5.73 +/- 0.11 cm/min and 1.53 +/- 0.05 min (-1), respectively. The hepatic extraction ratios of unbound GZ and GA in the IPL were 0.22 +/- 0.01 and 0.44 +/- 0.15, respectively. Seven hours after intra-portal venous injection in vivo, the cumulative biliary excretion ratio for GZ was 96 %. There was negligible biliary excretion of unchanged GA during the same period. It was apparent in all models used that in the absence of intestinal bacteria GZ was not metabolised to GA, or vice versa. Hence, GZ can be absorbed unchanged from the intestine provided it has sufficient time and is protected from intestinal bacteria. This opens up the possibility that the use of pharmaceutical carrier systems or similar formulation approaches may allow effective oral administration of therapeutic levels of GZ without the side effects associated with GA.

Extraction of nutraceutical compounds from licorice roots with subcritical water

Subcritical water (SBW) extraction of licorice root (LR) was carried out at four different temperatures (50, 100, 200, and 300 °C) for 10, 30, or 60 min, and nutraceutical compound levels of the SBW extracts were evaluated. SBW treatment of LR increased the antioxidant activity of extracts. Higher radical scavenging activity, reducing power, and total phenol content of the LR extracts were found when SBW extraction was carried at 200 °C for 60 min or at 300 °C for more than 30 min. The main active compounds such as glycyrrhetic acid (GA) and glycyrrhizin (GL) showed different extraction patterns. GA and GL were present at maximum levels following SBW extraction at 100 °C for 30 and 60 min, respectively. However, liquiritin (LQ), another nutraceutical compound of LR, showed the highest levels following extraction at 300 °C for 60 min. The results indicated that the temperature and time of SBW extraction significantly affected the antioxidant activities and nutraceutical compound levels of LR extracts.