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Glycyrrhetinic acid is an aglycone of glycyrrhizic acid, another major active component of licorice roots. Licorice root extract has been used for a long time as a medicine and a natural sweetening additive. In the present study, we found that glycyrrhetinic acid inhibits 12-O-tetradecanoylphorbol-13-acetate (TPA) mediated oxidative stress and tumor promotion in murine skin. Topical application of TPA alone in mouse skin enhances ornithine decarboxylase activity and also increases [3H]-thymidine incorporation in DNA. Topical application of TPA also resulted in the depletion of glutathione, activities of glutathione metabolizing and antioxidant enzymes. Application of glycyrrhetinic acid prior to TPA treatment reduces this enhanced ODC activity, [3H]-thymidine incorporation in DNA and oxidative stress. Glycyrrhetinic acid was also found to inhibit DMBA/TPA-induced skin tumor formation at doses of 1.25 and 2.5 mg by reducing the number of tumors per mouse by 24% (P < 0.05) and 62% (P < 0.05), respectively. These results suggest that glycyrrhetinic acid, an antioxidant, is a potential chemopreventive agent that can inhibit DMBA/TPA-induced cutaneous oxidative stress and tumor promotion.
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PMID:Inhibitory effect of 18beta-glycyrrhetinic acid on 12-O-tetradecanoyl phorbol-13-acetate-induced cutaneous oxidative stress and tumor promotion in mice. 1615 54

Much of the interest on the chemopreventive properties of licorice has been focused on the plant genius Glycyrrhiza glabra. In this study the ethanol extract of Chinese licorice root, Glycyrrhiza uralensis (G. uralensis) was investigated for its estrogenic effect and the ability to inhibit cell proliferation in the MCF-7 human breast cancer cell line. The extract of the root of G. uralensis was fractionated in EtOH:H(2)O (80:20) (80% ethanol). The extract exhibited estrogenic effects similar to 17beta- estradiol (E2) and induced apoptosis at the same dose level (100 microg/ml) in MCF-7 breast cancer cells, results were associated with up-regulation of tumor suppressor gene p53 and pro-apoptotic protein Bax. G. uralensis extract caused the up-regulation of p21(waf1/cip1) and down-regulation of cdk 2 and cyclin E and most significantly, induced G1 cell cycle arrest. This is the first study to show that the ethanolic extract of the root of G. uralensis has an estrogen-like activity and anti-cancer effects against MCF-7 human breast cancer cells. Whilst the use of phytoestrogens to protect against hormone-dependent cancers or as a 'natural' alternative to hormone replacement therapy remains controversial, the data in this paper support the suggestion that extracts of root of the Chinese licorice G. uralensis might be of importance in this debate.
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PMID:Chemopreventive properties of the ethanol extract of chinese licorice (Glycyrrhiza uralensis) root: induction of apoptosis and G1 cell cycle arrest in MCF-7 human breast cancer cells. 1629 10

Glycyrrhizin, the major bioactive component of Glycyrrhiza uralensis, is widely used as a natural sweetener. Recently glycyrrhizin has been shown to have anti-tumor activity, highly active in inhibiting replication of HIV-1 and SARS-associated virus and exhibits a number of pharmacological effects. The principle objective of the current study was to evaluate the effects of different spectral quality including red, blue, white and UV-B radiation on the production of glycyrrhizin, in a controlled environment. Plants were grown under artificial lights with elevated CO(2) concentration and both the pot and hydroponic plants were assigned to red and blue light treatments and those grown under white fluorescent lamps were used as control. In a separate experiment, pot plants were exposed to ultraviolet (UV)-B radiation (wavelength: 280-315 nm). The net photosynthetic rates (NPR) of the leaves reduced significantly immediately after exposure to the high intensity UV-B radiation (3 days at 1.13 W m(-2)). In case of the low intensity UV-B radiation (15 days at 0.43 W m(-2)), NPR was also reduced, but the rate of reduction was significantly slower than that of the high intensity treatment. The concentrations of glycyrrhizin quantified in the root tissues were highest in the plants grown under red light in both hydroponic and pot systems and the concentration increased linearly from 1- to 3-month-old pot plants. Both the low and high intensity of UV-B exposure increased the concentration of glycyrrhizin in the root tissues of 3-month-old pot plants, the values being nearly X1.5 those of the control. The results also indicate that the glycyrrhizin concentrations of 3-6 months old pot plants were similar or even higher than the previously reported values for 3-4 years old field-grown plants and confirm that high concentration of glycyrrhizin production is possible within a very short production period under controlled environments.
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PMID:Spectral quality and UV-B stress stimulate glycyrrhizin concentration of Glycyrrhiza uralensis in hydroponic and pot system. 1638 31

Blood vessel plays a crucial role in solid tumor development. It has been suggested that blocking of angiogenesis and the action of the cytokine VEGF could be possible in cancer therapy. In a screen for naturally occurring angiogenic inhibitors, we have identified an extract from the roots of Glycyrrhiza glabra, which has potent antiangiogenic and antitumor activity. The aqueous extract inhibits the in vivo and in vitro proliferation of Ehrlich ascites tumor cells. The angioinhibitory activity of G. glabra was confirmed by its inhibition of angiogenesis in in vivo assays, peritoneal and chorioallantoic membrane assay. Reduction in the levels of the cytokine VEGF and microvessel density count in the peritoneum of mice treated with G. glabra indicated that the plant extract decreased VEGF production and the cytokine induced neovascularization. Our results suggest that the extract from the roots of G. glabra may be a potential supplemental source for cancer therapy.
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PMID:Angiogenic and proliferative effects of the cytokine VEGF in Ehrlich ascites tumor cells is inhibited by Glycyrrhiza glabra. 1642 85

Epidemiological studies indicate that the intake of flavonoids is inversely associated with risk of stroke, cardiovascular diseases and cancer. Isoliquiritigenin (ISL), a flavonoid constituent in the root of Glycyrrhiza glabra, is known to have vasorelaxant effect, antioxidant, anti-platelet, anti-tumor, anti-allergic, antiviral activities and estrogenic properties. However, there is no report on the effects of ISL in cerebral ischemia. Evidence demonstrate that the impaired energy metabolism and the excessive generation of reactive oxygen radicals (ROS) contribute to the brain injury associated with cerebral ischemia. In the present study, the protective effects of ISL were investigated in transient middle cerebral artery occlusion (MCAO)-induced focal cerebral ischemia-reperfusion injury in rats. Male Sprague-Dawley rats were divided into five groups: sham-operated group, vehicle-pretreated group, and three ISL-pretreated groups (5, 10 and 20 mg kg(-1), i.g.). ISL were administered once a day, for 7 days prior to ischemia. The rats were subjected to 2 h right MCAO via the intraluminal filament technique and 22 h reperfusion. Pretreatment with ISL significantly reduced the cerebral infarct volume and edema and produced significant reduction in neurological deficits. In this study, in order to clarify the mechanism of ISL's protection against cerebral ischemia damage, cerebral energy metabolism, brain Na+K+ATPase activity, malondialdehyde (MDA) content and antioxidant enzyme activities were measured. ISL pretreatment increased the brain ATP content, energy charge (EC) and total adenine nucleotides (TAN) in a dose-dependent manner. The brain Na+K+ATPase activity was protected significantly by pretreatment of ISL for 7 days. Pretreatment with ISL significantly inhibited the increases of brain MDA content and prevented the activities of brain superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) from declines caused by cerebral ischemia-reperfusion. All these findings indicate that ISL has the protective potential against cerebral ischemia injury and its protective effects may be due to the amelioration of cerebral energy metabolism and its antioxidant property.
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PMID:Protective effects of isoliquiritigenin in transient middle cerebral artery occlusion-induced focal cerebral ischemia in rats. 1645 97

Agrobacterium strains have been frequently isolated from the root nodules of different legumes. Various possible mechanisms have been proposed to explain the existence of these bacteria in nodules, but there is no sufficient experimental evidence to support the estimations. In this work, we proved that the Agrobacterium strain CCBAU 81181, which was originally isolated from the root nodules of Onobrychis viciaefolia, and a symbiotic strain of Sinorhizobium meliloti CCBAU 10062 could coinhabit the root nodules of Melilotus dentatus. Analyses were performed by using a fluorescence marker, reisolation of bacteria from nodules, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of whole cellular proteins, and polymerase chain reaction amplification of symbiotic genes. The inoculation of A. tumefaciens CCBAU 81181 did not affect the growth and nodulation of plants. CCBAU 81181 and 24 other Agrobacterium strains isolated from nodules were incapable of nodulating on their original or alternative host and 22 strains of these strains were endophytes in the roots and stems of their hosts. Also, the tumor-inducing A. tumefaciens strains IAM 13129(T) and C58 were found capable of entering the roots of Glycyrrhiza pallidiflora, but did not cause pathogenic symptoms. With these results, we conclude that A. tumefaciens strains could be endophytic bacteria in the roots, stems, and root nodules. This finding partially explains why Agrobacterium strains were frequently isolated from the surface-sterilized nodules.
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PMID:Endophytic occupation of root nodules and roots of Melilotus dentatus by Agrobacterium tumefaciens. 1689 96

Chemoprofile of Taverniera cuneifolia (Roth) Arn. a wild relative of commercial licorice (Glycyrrhiza glabra L) is presented. Both T. cuneifolia and G. glabra L were found to be very similar phytochemically. At least eighteen chromatophores were found similar in both the plants including the sweetening principle, glycyrrhizin. The extracts of T. cuneifolia root, exhibited promising anti-inflammatory, anti-tumor, anti germ tube formation (in Candida albicans), protection from mutagen toxicity and cytotoxic activities comparable to that of G. glabra. In general, the results suggest that T. cuneifolia could be used as substitute of G. glabra.
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PMID:Chemoprofile and bioactivities of Taverniera cuneifolia (Roth) Arn.: a wild relative and possible substitute of Glycyrrhiza glabra L. 1735 Feb 39

Licochalcones A (1) and E (2), retrochalcones or reversely constructed chalcones, isolated from the roots of Glycyrrhiza inflata, were evaluated for their cytotoxicities against four different human tumor cell lines; A549 (lung), SK-OV-3 (ovarian), SK-MEL-2 (melanoma) and HCT-15 (colon), using the sulforhodamine B (SRB) assay. The effects of these compounds toward the DNA topoisomerase I (topo I) inhibitory activity were also measured using the supercoiled DNA unwinding assay. All compounds showed moderate cytotoxicities against the four different human tumor cell lines and inhibited the topo I activity in dose-dependent manners. The inhibition of topo I by licochalcones A (1) and E (2) may explain the cytotoxicities of these compounds against the human tumor cell lines.
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PMID:Topoisomerase I inhibition and cytotoxicity of licochalcones A and E from Glycyrrhiza inflata. 1742 36

Licochalcones have a variety of biological properties including anti-tumor, anti-parasitic and anti-bacterial activities. Recently, a new retrochalcone (licochalcone E, Lico-E) was isolated from the roots of Glycyrrhiza inflata (Chem. Pharm. Bull., 53, 2005, Yoon et al.) by cytotoxicity-guided fractionation. This study examined whether or not Lico-E-induced endothelial cell death occurs through apoptosis, and investigated molecular mechanisms involved in this process. Lico-E was found to suppress ECV304 cell growth and induce apoptosis. The induction of apoptosis by Lico-E was confirmed by the ladder-patterned DNA fragmentation, the presence of cleaved and condensed nuclear chromatin and the increased number of annexin V-positive cells. Lico-E could effectively inhibit the constitutive NF-kappaB activation, as revealed by the electrophoretic mobility shift assay and NF-kappaB-dependent luciferase reporter study. In addition, the Lico-E treatment caused a change in the Bax/Bcl-2 ratio that favored apoptosis. These results suggest that Lico-E induces endothelial cell apoptosis by modulating NF-kappaB and the Bcl-2 family.
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PMID:Induction of apoptosis by the licochalcone E in endothelial cells via modulation of NF-kappaB and Bcl-2 Family. 1805 14

Glycyrrhiza uralensis (Leguminosae) has long been known as an antiinflammatory agent for gastric ulcers, arthritis, and rheumatism. The flavonoid glycyrol (GC) (10 microg/ml) isolated from G. uralensis dramatically inhibits phorbol ester (phorbol 12-myristate 13-acetate)-induced nuclear factor (NF)-kappaB-dependent transcriptional activity, as determined by luciferase reporter activity in human kidney epithelial 293T cells. To investigate global gene expression profiling in cells by GC, we performed high-density oligonucleotide microarrays. Our microarray analyses showed that GC inhibited phorbol ester-induced NF-kappaB-dependent transcriptional activity in inflammatory-related gene expression. RT-PCR analysis, based on microarray data, showed that NF-kappaB-dependent genes (such as CCL2, CCL7, CD44, and HSPB8 in addition to NF-kappaB itself) were significantly downregulated by GC. Treatment with GC (10 microg/ml) inhibited I-kappaB degradation induced by phorbol 12-myristate 13-acetate. The microarray data also suggested that GC induces gene expression to p53-dependent apoptosis through endonuclease G, instead of CAD/DFF and AIF/PDCD8, as a downstream-apoptosis factor in human kidney epithelial 293T tumor cells, and induces oncogenes with a suppressor role as an added function.
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PMID:Gene induction by glycyrol to apoptosis through endonuclease G in tumor cells and prediction of oncogene function by microarray analysis. 1841 17


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