Pharmaceutical evaluation of Glycyrrhiza uralensis roots cultivated in eastern Nei-Meng-Gu of China. (1/21)

To clarify the feasibility of medicinal use of the cultivated Glycyrrhiza resources, the equivalency between the G. uralensis roots cultivated in eastern Nei-Meng-Gu of China and medicinal licorice (Glycyrrhizae Radix, Gancao in Chinese and Kanzo in Japanese) was examined. The HPLC fingerprint including glycyrrhizin (GL) of the cultivated roots was similar to that of medicinal Gancao, but different from that of non-medicinal Xinjiang-Gancao (Shinkyo Kanzo in Japanese). Similarity between the cultivated roots and two medicinal Gancao was confirmed quantitatively by hierarchical cluster analysis on the basis of HPLC-7-peak-area data. Moreover, the 4-year-old adventitious roots conformed to the five standards described in the Japanese Pharmacopoeia XIV (JP XIV). The 4-year-old adventitious roots had similar pharmaceutical properties to those of medicinal Dongbei-Gancao (Tohoku Kanzo in Japanese) as determined by examining IgE-mediated triphasic skin reaction in mice and pharmacokinetic profile of glycyrrhetic acid, an anti-allergic metabolite of GL. The present pharmaceutical study suggests that the 4-year-old adventitious roots of G. uralensis cultivated in eastern Nei-Meng-Gu of China are comparable to medicinal Gancao conforming to the JP XIV, and may be a potential medicinal source to compensate for the insufficiency of wild Glycyrrhiza plants caused by collection restriction in China.  (+info)

Comparative pharmacokinetic behavior of glycyrrhetic acid after oral administration of glycyrrhizic acid and Gancao-Fuzi-Tang. (2/21)

Comparative pharmacokinetic profiles of glycyrrhetic acid (GA), glycyrrhizic acid (GL) and Gancao-Fuzi-Tang (KF) after oral administration of GL and KF were studied. Plasma samples taken from rats were acidified with acetic acid and GA was extracted with isopropanol-ethyl ether (1 : 1). Separation of GA was performed on a C(18) column with the detection wavelength set at 254 nm. The mobile phase was methanol-acetonitrile-water-acetic acid (58 : 18 : 24 : 1 v/v). The results showed that the mean residence time and area under the curve of GA in KF-administered rats were 27.6+/-1.5 h and 122.8+/-46.7 microg.h/ml respectively, which were significantly different from those in GL-administered rats (15.0+/-2.0 h and 40.9+/-9.6 microg.h/ml, respectively). The results suggest the increased effect of GA after oral administration of KF in comparison with GL.  (+info)

Comparative analysis of ten strains of Glycyrrhiza uralensis cultivated in Japan. (3/21)

Comparative analysis of 10 strains of Glycyrrhiza uralensis cultivated in Kyoto, Japan, was undertaken to characterize their variations. Based on the chemical characteristics of their leaves and underground parts, the 10 strains were divided into two chemotypes, the China type and Kazakhstan type. The contents of licoleafol in the leaves of the China type (0-0.03% of dry weight) were lower than those of the Kazakhstan type (0.05-1.16% of dry weight). In addition, a China type-specific unidentified compound was also detected in the leaves of China-type plants. Glycyrrhizin contents in the underground parts of the China type (2.08-5.12% of dry weight) were relatively higher than those of the Kazakhstan type (0.75-2.55% of dry weight). Contents of glycycoumarin, a species-specific flavonoid of G. uralensis, in the underground parts of China-type plants (0.07-0.28% of dry weight) were higher than those of Kazakhstan-type plants (0.01-0.08% of dry weight). These 10 strains were also divided into two genotypes, the GA type and AT type, based on their chloroplast ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit gene (rbcL) sequences, although there was no correlation between the chemotype and the rbcL genotype.  (+info)

Traditional Chinese medicines Wu Wei Zi (Schisandra chinensis Baill) and Gan Cao (Glycyrrhiza uralensis Fisch) activate pregnane X receptor and increase warfarin clearance in rats. (4/21)

The traditional Chinese medicines (TCMs) are essential components of alternative medicines. Many TCMs are known to alter the expression of hepatic drug-metabolizing enzymes and transporters. The molecular mechanism by which TCMs and/or their constituents regulate enzyme and transporter expression, however, has remained largely unknown. In this report, we show that two TCMs, Wu Wei Zi (Schisandra chinensis Baill) and Gan Cao (Glycyrrhiza uralensis Fisch), and their selected constituents activate the xenobiotic orphan nuclear receptor pregnane X receptor (PXR). Treatment with TCM extracts and the Schisandrol and Schisandrin constituents of Wu Wei Zi induced the expression of drug-metabolizing enzymes and transporters in reporter gene assays and in primary hepatocyte cultures. The affected enzymes and transporters include CYP3A and 2C isozymes and the multidrug resistance-associated protein 2. In transient transfection and reporter gene assays, the Schisandrin constituents of Wu Wei Zi had an estimated EC50 of 2 and 1.25 microM on hPXR and mPXR, respectively. Interestingly, mutations that were intended to alter the pore of the ligand-binding cavity of PXR had species-specific effects on the activities of the individual Schisandrols and Schisandrins. In rats, the administration of Wu Wei Zi and Gan Cao increased the metabolism of the coadministered warfarin, reinforcing concerns involving the safe use of herbal medicines and other nutraceuticals to avoid PXR-mediated drug-drug interactions. Meanwhile, the activation of PXR and induction of detoxifying enzymes provide a molecular mechanism for the hepatoprotective effects of certain TCMs.  (+info)

A LuxR/LuxI-type quorum-sensing system in a plant bacterium, Mesorhizobium tianshanense, controls symbiotic nodulation. (5/21)

The ability of rhizobia to symbiotically fix nitrogen from the atmosphere when forming nodules on their plant hosts requires various signal transduction pathways. LuxR-LuxI-type quorum-sensing systems have been shown to be one of the players in a number of rhizobium species. In this study, we found that Mesorhizobium tianshanense, a moderate-growth Rhizobium that forms nodules on a number of licorice plants, produces multiple N-acyl homoserine lactone (AHL)-like molecules. A simple screen for AHL synthase genes using an M. tianshanense genomic expression library in Escherichia coli, coupled with a sensitive AHL detector, uncovered a LuxI-type synthase, MrtI, and a LuxR-type regulator, MrtR, in M. tianshanense. Deletions of the mrtI or mrtR locus completely abolished AHL production in M. tianshanense. Using lacZ transcriptional fusions, we found that expression of the quorum-sensing regulators is autoinduced, as mrtI gene expression requires MrtR and cognate AHLs and mrtR expression is dependent on AHLs. Compared with the wild-type strains, quorum-sensing-deficient mutants showed a marked reduction in the efficiency of root hair adherence and, more importantly, were defective in nodule formation on their host plant, Glycyrrhiza uralensis. These data provide strong evidence that quorum sensing plays a critical role in the M. tianshanense symbiotic process.  (+info)

Isoliquiritigenin, one of the antispasmodic principles of Glycyrrhiza ularensis roots, acts in the lower part of intestine. (6/21)

Glycyrrhizae radix is used to treat abdominal pain as a component of shakuyakukanzoto (shaoyao-gancao-tang), a traditional Chinese medicine formulation. Previously, we have reported the isolation of glycycoumarin as a potent antispasmodic with an IC50 value of 2.93+/-0.94 microM for carbamylcholine (CCh)-induced contraction of mouse jejunum from an aqueous extract of Glycyrrhizae radix (licorice), and clarified that its mechanism of action involves inhibition of phosphodiesterase 3. The purpose of the present study was to examine an antispasmodic principle of licorice other than glycycoumarin. Isoliquiritigenin was isolated from an aqueous extract of licorice as a potent relaxant, which inhibited the contraction induced by various types of stimulants, such as CCh, KCl, and BaCl2 with IC50 values of 4.96+/-1.97 microM, 4.03+/-1.34 microM and 3.70+/-0.58 microM, respectively, which are close to those of papaverine. However, the amount of isoliquiritigenin in the aqueous extract of licorice was very small. When the aqueous licorice extract was treated with naringinase, the amounts of glycosides such as isoliquiritin, which were abundant but had much less potent relaxant activity, were decreased while isoliquiritigenin was increased. At the time, the relaxant activity of the treated sample was increased significantly, shifting the IC50 from 358+/-104 to 150+/-38 microg/ml for CCh-induced contraction. Isoliquiritigenin also showed the most potent inhibition of mouse rectal contraction induced by CCh with an IC50 value of 1.70+/-0.07 microM. These results suggest that isoliquiritigenin acts as a potent relaxant in the lower part of the intestine by transformation from its glycosides.  (+info)

Changes in components, glycyrrhizin and glycyrrhetinic acid, in raw Glycyrrhiza uralensis Fisch, modify insulin sensitizing and insulinotropic actions. (7/21)

We hypothesized that roasted Glycyrrhizae Radix (Glycyrrhizin Radix Praeparata, GRP) might modify anti-diabetic action due to compositional changes. Then we examined the anti-diabetic effect and mechanism of raw Glycyrrhizae Radix (GR) and GRP extracts and their major respective components, glycyrrhizin and glycyrrhetinic acid. In partial pancreatectomized (Px) diabetic mice, both GR and GRP improved glucose tolerance, but only GRP enhanced glucose-stimulated insulin secretion as much as exendin-4. Both GR and GRP extracts enhanced insulin-stimulated glucose uptake through peroxisome proliferation-activated receptor (PPAR)-gamma activation in 3T3-L1 adipocytes. Consistently with the results of the mice study, only GRP and glycyrrhetinic acid enhanced glucose-stimulated insulin secretion in isolated islets. In addition, they induced mRNA levels of insulin receptor substrate-2, pancreas duodenum homeobox-1, and glucokinase in the islets, which contributed to improving beta-cell viability. In conclusion, GRP extract containing glycyrrhetinic acid improved glucose tolerance better than GR extract by enhancing insulinotropic action. Thus, GRP had better anti-diabetic action than GR.  (+info)

Constituent properties of licorices derived from Glycyrrhiza uralensis, G. glabra, or G. inflata identified by genetic information. (8/21)

Constituent properties of licorices derived from Glycyrrhiza uralensis, G. glabra, and G. inflata are revealed by comparing 117 of licorice identified using four genetic markers; internal tracscribed spacer (ITS) on nuclear ribosomal DNA, rbcL gene, matK gene, and trnH-trnK1 intergenic region on chloroplast DNA. Regarding six main constituents of licorice; glycyrrhizin, liquiritin, liquiritin apioside, isoliquiritin, isoliquiritin apioside, and liquiritigenin, the constituent property of G. glabra resembles to that of G. inflata. On the other hand, the constituent property of G. uralensis is not similar to that of G. glabra or G. inflata and is characterized by a wide content variation of the six constituents compared to those of G. glabra and/or G. inflata. The mean contents of liquiritin, isoliquiritin, or liquilitigenin in G. uralensis are significantly higher than those of G. glabra or G. inflata. Therefore, the licorice species should be selected depending on these constituent properties for the traditional Chinese medicines or the Japanese Kampo medicines. Additionally, glycycoumarin, glabridin, and licochalcone A were reconfirmed as the species-specific typical constituents of G. uralensis, G. glabra, and G. inflata respectively. Therefore, it is resulted that the determination of the three species-specific constituents may be useful for the species identification of licorice. However, since 6% of licorice examined and hybrids were exceptions to the rule, their genetic information is necessary for the accurate species identification of licorice.  (+info)

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