• Proceedings of the PSK Conference
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• 2002.04a
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• pp.204.1-204.1
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• 2002

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.80.1-80.1
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• 2003

Intestinal epithelial cells can produce cytokines and chemokines that play an important role in the mucosal immune response. Regulation of this production is important to prevent inflammatory tissue damage. Glycyrrhiza glabra has been shown to inhibit inflammation. The aim of this study was to examine the inhibitory effect of 18- beta-glycyrrhetinic acid, a triterpenoid saponin of Glycyrrhiza glabra, on IL-S production via mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-kB) in TNF-alpha-stimulated human colon epithelial cells. (omitted)

• Journal of Applied Biological Chemistry
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• v.53 no.3
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• pp.147-153
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• 2010

$\beta$-glycyrrhetinic acid (GA), the active principle of licorice (Glycyrrhiza glabra L.) has been reported to exhibit anti-inflammatory properties in different animal models. In this study, the effects of GA on the production of inflammatory mediators including tumor necrosis factor (TNF)-$\alpha$, interleukin (IL)-6, nitric oxide (NO), and prostaglandin E (pGE)-2 were examined in RAW 264.7 cells in vitro. Furthermore, to elucidate a possible mechanism for the inhibitory effect of GA on the production of TNF-$\alpha$, it was investigated whether the treatment of GA affects the I-${\kappa}B{\alpha}$ degradation and subsequent nuclear translocation of NF-${\kappa}B$. Various inflammatory responses were induced in the culture system by treating with a lipopolysaccharide (LPS). GA showed anti-inflammatory activities in dose-dependant manner with $IC_{50}$ of $5.4{\mu}M$ by inhibiting the production of TNF-$\alpha$ in RAW 264.7 cells. In addition, the treatment of GA blocked both I-${\kappa}B{\alpha}$ degradation and the nuclear translocation of NF-${\kappa}B$ from cytosol to nucleus. However, it did not affect the production of IL-6, NO, and PGE-2, implying the direct blocking of the production of TNF-$\alpha$ resulting from both the I-${\kappa}B{\alpha}$ degradation and the nuclear translocation of NF-${\kappa}B$. This finding might provide the underlying mechanism to explain the reported anti-inflammatory activities of GA in animal models.

• YAKHAK HOEJI
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• v.55 no.1
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• pp.39-44
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• 2011

Many reports indicate that $18{\beta}$-glycyrrhetinic acid ($18{\beta}$-GA) from Glycyrrhizae Radix has anti-inflammatory and immunoregulatory activities, whereas reports regarding anticancer activity of the compound are few. In present study, we investigated antitumor effect of $18{\beta}$-GA on tumor caused by A549 cancer cell in mice. Data resulting from the cytotoxicity assay showed that $18{\beta}$-GA caused killing of A549 cells. $LD_{50}$ values of $18{\beta}$-GA were app. 180 ${\mu}M$ and 80 ${\mu}M$, corresponding to 48 hr- and 72 hr-treatments, displaying that the killing activity was more effective as the $18{\beta}$-GA treatment was prolonged. Based on these data, antitumor effect of $18{\beta}$-GA was tested in nude mice. For induction of the tumor, A549 ($3{\times}10^6$ cells/mouse) was injected subcutaneously into the lateral abdomen of nude mice (Balb/c nu/nu). To determine the antitumor effect, nude mice with tumor were given $18{\beta}$-GA (1 mg/200 ${\mu}l$/mouse) intraperitoneally every three days for four times. Tumor-sizes were measured with a caliper for a period of 24 days. Results showed that the $18{\beta}$-GA treatment reduced the tumor-sizes (P<0.05) as compared with negative control nude mice that received diluent (DPBS). The reduction degree was greater than reduction degree by doxorubicin (60 ${\mu}g$/mouse), and the pattern of reduction was almost sustained during the entire period of the observation. In conclusion, our studies demonstrate that $18{\beta}$-GA has antitumor activity to the A549 cancer cell-caused tumor.

• YAKHAK HOEJI
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• v.35 no.3
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• pp.174-181
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• 1991

These experiments were conducted to investigate the effects of glycyrrhizin(GL) and glycyrrhetinic acid(GA) on histamine synthesis, lymphocyte blastogenesis in C57BL/6J mice splenocytes, IL-1 production, $Ca^{2+}$ uptake by macrophage-like P388D$_{1}$ cells and plaque forming cell assay against SRBC. Histamine contents, lymphocyte blastogenesis, IL-1 activity, $Ca^{2+}$ uptake and plaque forming cell were determined by enzyme isotope method, [sup 3/H]-thymidine incorporation, C3H/HeJ mouse thymocytes proliferation, the addition of 5 $\mu$Ci/ml $^{45}$Ca$^{2+}$ to P388D$_{1}$, cell suspension and assay to sheep red blood cell, respectively. Cytotoxicity, which was expressed as 50% mortality, was occurred by the addition of GL(10$^{-3}$M) and GA(10$^{-4}$M). Histamine production in mouse spleen cell culture was significantly increased by the addition of 0.25 $\mu\textrm{g}$/ml of Con A, after 48 hour incubation. Con A dependent T-lymphocyte proliferation was also enhanced by the addition of 0.25 .mu.g/ml of Con A. The effects of GL on histamine contents and T-lymphocyte proliferation were significantly decreased at high dose (10$^{-5}$M), while IL-1 activity was remarkably suppressed by 10$^{-8}$~10$^{-4}$M of GL. $Ca^{2+}$ uptake was not changed, but antibody production was increased by GL(10 mg/kg). GA inhibited histamine contents at 10$^{-9}$~10$^{-7}$ and depressed Con A (0.25 $\mu\textrm{g}$/ml) dependent T-lymphocyte proliferation at 10$^{-7}$~10$^{-5}$M of GA, but increased suboptimal dose (Con A 0.1 $\mu\textrm{g}$/ml) at 10$^{-9}$~10$^{-7}$M of GA. IL-1 activity was suppressed by 10$^{-8}$~10$^{-4}$M of GA and $Ca^{2+}$ uptake was enhanced by 10$^{-9}$~10$^{-6}$ of GA, but antibody production was not changed by GA. From the above results, it is suggested that GL and GA have immuno-regulatory action. GL decreased cell-mediated immune response, and increased humoral immune response at high dose. On the other hand, low dose of GA enhanced cell-mediated immune response, while high doses of GA decreased humoral immune reaction.

• The Korea Journal of Herbology
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• v.31 no.6
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• pp.73-81
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• 2016

Objectives : $18{\beta}$-Glycyrrhetinic acid (18betaGA) is an metabolite of glycyrrhizin in Glycyrrhiza (licorice). The present study investigated anti-inflammatory and anti-apoptosis effect of 18betaGA on the brain tissue of lipopolysaccharide (LPS)-treated C57BL/6 mice. Methods : 18betaGA was administered orally with low (30 mg/kg) and high (100 mg/kg) doses for 3 days prior to LPS (3 mg/kg) injection. Pro-inflammatory cytokines mRNA including tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin (IL)-$1{\beta}$, IL-6, and inflammatory enzyme cyclooxygenase-2 (COX-2) mRNA were measured in the cerebral cortex, hippocampus, and hypothalamus tissue using real-time polymerase chain reaction at 24 h after the LPS injection. Histological changes of Cornu ammonis area 1 (CA1) neurons, Bax, Bcl-2, and caspase-3 expression in the hippocampus was also evaluated by immunohistochemistry and Western blotting method. Results : 18betaGA significantly attenuated the up-regulation of TNF-${\alpha}$, IL-$1{\beta}$, IL-6 mRNA, and COX-2 mRNA expression in the brain tissues induced by the LPS injection. 18betaGA also significantly attenuated the reductions of the thickness of CA1 and the number of CA1 neurons. The up-regulation of Bax protein expression in the hippocampal tissue by the LPS injection was significantly attenuated, while the ratio of Bcl-2/Bax expression was increased by 18betaGA treatment. 18betaGA also significantly attenuated the up-regulation of Bax and caspase-3 expression in the CA1 of the hippocampus. Conclusion : This results indicate that 18betaGA has anti-inflammatory and anti-apoptosis effect under neuroinflammation induced by the LPS injection and suggest that 18betaGA may be a beneficial drug for various brain diseases accompanied with the brain tissue inflammation.

• YAKHAK HOEJI
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• v.6 no.1
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• pp.25-27
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• 1962

The derivative of glycyrrhetinic acid which have similar effects of desoxycorticosterone acetate was prepared glycyrrhetinyl chloride by the chlorination with thionyl chloride at low temperature. 2-Acetyl-11-keto-.DELTA. : 13 oleanolic ketol acetate (30) was synthesized by diazotating glycyrrhetinyl chloride with diazomethan and the acetylation with anhydro acetic acid. 2-Acetyl-.DELTA.12 : 13 oleanolic ketol acetate (28) was synthesized by chlorinating oleanolic acid with thionyl chloride, and by diazotatating oleanolyl chloride with diazomethan and the acetylation with anhydroacetic acid.

• Korean Journal of Pharmacognosy
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• v.24 no.2
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• pp.159-165
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• 1993

The studies were conducted to investigate the effect of Sinhyo-Taklee-San(STS), which is composed of Astragali Radix(AR), Lonicerae Flos(LF), Angelicae gigantis Radix(AGR) and Glycyrrhizae Radix(GR), on the proliferation of fibroblast cell(Balb/c 3T3). STS, GR and glycyrrhizin increased the proliferation of 3T3 cells. The 10% serum obtained from STS, AR, LF, AGR and GR treated mice also increased the proliferation of 3T3 cells markedly. GR, glycyrrhizin and glycyrrhetinic acid inhibited protein synthesis, but did not affect on DNA synthesis.

• 대한상한금궤의학회지
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• v.8 no.1
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• pp.1-23
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• 2016

Objectives : The purpose of this paper is to find out the safe dose and clinical use for administration of Glycyrrhizae Radix in Shanghanlun(傷寒論). Methods : Web-databases(OASIS, NDSL, Pubmed, Google) were searched with keywords including 'Licorice', 'Pseudoaldosteronism', 'Glycyrrhizin', 'Testosterone' on 14/10/2016. The searched about 40 papers and books were reveiwed. Results : Glycyrrhizin(GL) and 3-monoglucuronyl glycyrrhetinic acid(3MGA) in Glycyrrhizae Radix are found to be the main compounds vulnerable for inducing pseudoaldosteronism. The dose range of Glycyrrhizae Radix in Shanghanlun prescriptions is from 0.25 g to 12 g as a daily administration, and this dose satisfies the guidelines of WHO, European Union, ABC etc. And risk factors contributing for personal sensitivities are old age(>60), female sex, liver dysfunction, hypokalemia, prolonged gastrointestinal transit time, anorexia nervosa, decreased 11-${\ss}$-hydroxysteroid dehydrogenase-2 activity and hypertension. Conclusions : As a result, dose of Glycyrrhizae Radix in Shanghanlun(傷寒論) is safe. However, the personal sensitivity and unexpected drug interactions are independent from doses of GL, so doctors should monitor those risk factors and symptoms of pseudoaldosteronism when administering Glycyrrhizae Radix.

• Korean Journal of Pharmacognosy
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• v.30 no.3
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• pp.269-274
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• 1999

To analyze scientifically the prescription principle of polyprescriptions (Gamchotang, Daewhanggamchotang, Jakyakgamchotang, Gamchogungangtang and Gilkyungtang) containing Glycyrrhizae Radix, the transforming rate of glycyrrhizin in these polyprescriptions to 18 ${\beta}-glycyrrhetinic$ acid and their inhibitory effect on ${\beta}-glucuronidase$, hyaluronidase, phosphodiesterase and trypsin were investigated. When Glycyrrhizae Radix containing polyprescriptions were extracted with water, the contents of glycyrrhizin in water extract of Glycyrrhizae Radix with Rhei Rhizoma or with Zingiberis Rhizoma were higher than that of Glycyrrhizae Radix only, but that in water extract of Glycyrrhizae Radix with Platicodi Radix was lower than that of Glycyrrhizae Radix only. By human intestinal bacteria, glycyrrhizin was metabolized to 18 ${\beta}-glycyrrhetinic$ acid. These metabolism of glycyrrhizin in polyprescriptions containing Glycyrrhizae Radix was inhibited by Rhei Rhizoma, Paeoniae Radix and Platicodi Radix, but was not affected by Zingiberis Rhizoma. The inhibitory activity of Glycyrrhizae Radix on hyaluronidase and ${\beta}-glucuronidase$, was synergistic with Rhei Rhizoma or Zingiberis Rhizoma, but was antagonistic by Platicodi Radix.