• 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.

• 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.

• Archives of Pharmacal Research
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• v.23 no.2
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• pp.172-173
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• 2000

The relationship between the metabolites of glycyrrhizin (18$\beta$-glycyrrhetinic acid-3-O--D-glu-curonopyranosyl-($1{\rightarrow}2$)-$\beta$-D-glucuronide, CL) and their biological activities was investigated. By human intestinal microflora, CL was metabolized to 18$\beta$-glycyrrhetinic acid (GA) as a main product and to 18$\beta$-glycyrrhetinic acid-3-O-$\beta$-D-glucuronide (GAMG) as a minor product. The former reaction was catalyzed by Eubacterium L-8 and the latter was by Streptococcus LJ-22. Among GL and its metabolites, GA and GAMG had more potent in vitro anti-platelet aggregation activity than GL. GA also showed the most potent cytotoxicity against tumor cell lines and the potent inhibitory activity on rotavirus infection as well as growth of Helicobacter pylori. GAMG, the minor metabolite of GL, was the sweetest.

• Journal of Microbiology and Biotechnology
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• v.15 no.4
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• pp.792-799
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• 2005

Two novel $\beta$-glucuronidases, which metabolize glycyrrhizin (GL) to 18$\beta$-glycyrrhetinic acid-3-O-$\beta$-D-glucuronide (GAMG), were purified from Streptococcus LJ-22 isolated from human intestinal microflora. $\beta$-Glucuronidases I and II were purified to apparent homogeneity, using a combination of ammonium sulfate fractionation, butyl toyopearl, Q-Sepharose, hydroxyapatite Ultrogel, and GL-attached Sepharose column chromatographies, with the final specific activities of 137 and 190 nmole/min/mg, respectively. The molecular sizes of both $\beta$-glucuronidases were found to be 140 kDa by gel filtration, and they consisted of two identical subunits (M.W. 67 kDa by SDS-PAGE). $\beta$-Glucuronidases I and II showed optimal activity at pH 7.0 and pH 6.5, respectively. Both purified enzymes were potently inhibited by $Cu^{2+}$ and PCMS, and had maximum activity on glycyrrhizin, but did not hydrolyze p-nitrophenyl-$\beta$-glucuronides, baicalin, or GAMG These findings suggest that the biochemical properties and substrate specificities of these enzymes are different from those of the previously purified $\beta$-glucuronidases. This is the first reported purification of sugar (not aglycone)-recognizing $\beta$-glucuronidases from intestinal bacteria.

• Korean Journal of Pharmacognosy
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• v.27 no.3
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• pp.196-206
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• 1996

In order to characterize the chemical change, of the constituents and pharmacological transformation of Glycyrrhizae Radix(GR) which may occur during its processing, processed GR has been investigated in comparison with unprocessed GR. It was found that glycyrrhizin(GL) and other several constituents contained in GR were remarkably changed by processing, and the decrease of contents of GL was identified by making use of thin layer chromatography-chromatoscanner. And also, it was found that glycyrrhetic acid (GA) was identified from processed GR. We recognized that commonly processed GR showed less hemolytic effect than unprocessed GR and processed GR at $190{\circ}c$. It was also found that commonly processed GR showed more effective analgesic effect and prolonged the duration of hypnosis induced by pentobarbital-Na in mice as compared with corresponding unprocessed GR and processed GR at $190{\circ}c$. And then, commonly processed GR significantly suppressed the increases of s-GOT, s-GPT and s-LDH activities in injured mice induced by $CCl_4$.

• Korean Journal of Pharmacognosy
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• v.36 no.3 s.142
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• pp.209-219
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• 2005

In this study, we carried out the preparing standardization and regulation of processed Glycyrrhizae Radix (PGR) which have been widely used in oriental medicines. Glycyrrhizae Radix(GR) have been generally prepared by the stir-frying, or mix-frying with honey for the purpose of decreasing sweetness and augmenting vitality. Firstly, we tried to standardize PGR prepared by the stir-frying. We purchased 14 kinds of PGR and non-processed GR(NPGR) at oriental physician's offices and oriental pharmacies on a nation scale, respectively. The amounts of dry on loss, water extract, diluted ethanol extract, ether extract, total ash, acid insoluble ash, glycyrrhizin(GL), glycyrrhetic acid(GA) and liquiritin(LQ) of them were examined. The amounts of dry on loss, GL and LQ in commercial PGRs showed remarkable decrease, while GA showed increased as compared with NPGR. In order to standardize preparing method of PGR, the effect of heating time on physico-chemical parameters and biological activities were examined. Physico-chemical parameters such as dry on loss, extract amount, GL and LQ contents in PGRs showed decrease, however, GA was increased with heating time as compared with NPGR. Also, GA, obtained from heat-treated GR, was found as an artifact in PGRs. PGR was more effective than NPGA in vitro test of DPPH scavenging effect and TBA-Rs reducing effect. PGR and NPGR showed potent hepatoprotective effect on $CCl_4-intoxicated$ rats. Especially, PGR prepared by 80 min of heating was the most effective. Considering these results, the optimal condition for PGR preparation was $150^{\circ}C$ for 80 min.