• 약학회지
• /
• 제52권6호
• /
• pp.494-499
• /
• 2008

The role of antibody in the fungal infections is controversial. However, our previous reports showed a certain epitope in Candida albicans cell wall (CACW) induces protective antibody. A major problem is that the epitope isolation requires tremendous time with high cost. This aspect led us to investigate a simple way inducing protective antibodies against C. albicans. In the present study, we determined if $18{\beta}$-glycyrrhetinic acid ($18{\beta}$-GA) from Glabrae Radix (a family of Leguminosae) has immunoadjuvant activity. Data displayed that the $18{\beta}$-GA suppressed proliferations of both T- and Blymphocytes at high concentrations, whereas below 20 ${\mu}M$ concentration the compound supported the proliferations. These observations indicate that $18{\beta}$-GA has immunoregulatory activity. Based on this observation, an immunoadjuvant effect was examined at the low concentration. Results from animal experiments showed that CACW combined with or without $18{\beta}$-GA produced the anti-C. albicans antiserum in mice. Nevertheless, the CACW combined with $18{\beta}$-GA formula only protected mice against disseminated candidiasis (P<0.05). These data implicate that $18{\beta}$-GA has immunoadjuvant activity, which may provoke the CACW antigen to induce protective antibody. Currently, we are investigating possible mechanism of how the $18{\beta}$-GA provokes such protective immunity against the disseminated disease.

• 약학회지
• /
• 제55권1호
• /
• pp.39-44
• /
• 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.

• 약학회지
• /
• 제59권4호
• /
• pp.164-169
• /
• 2015

In the present study, we determined the effect of $18{\beta}$-glycyrrhetinic acid ($18{\beta}$-GA) in the mice model bearing xenografts of HT-29 human colon cancer cell line. Data from the cytotoxicity assay displayed that $18{\beta}$-GA induced cell death in HT-29. The cytotoxicity was enhanced as the $18{\beta}$-GA treatment was prolonged. In case of 72 hrs treatment, $LD_{50}$ of $18{\beta}$-GA was approximately $90{\mu}M$, and the efficacy at $100{\mu}M$ of $18{\beta}$-GA appeared to be equivalent to that of doxorubicin at $1{\mu}M$. Based on the in vitro data, we tested the anti-tumor effect of $18{\beta}$-GA in thymic mice (Balb/c strain). Xenograft tumors were generated by subcutaneous injection of HT-29 ($3{\times}10^6cells/mouse$) to mice and the mice were treated intraperitoneally with $18{\beta}$-GA ($50{\mu}g/time/mouse$) every other day for 4 times. The tumor volumes were measured for a period of 14 days. Data displayed that the $18{\beta}$-GA treatment reduced the tumor volumes (P < 0.05) as compared to control mice. However, this activity was demolished when athymic mice (Balb/c nu/nu) were used instead of thymic mice. This observation appeared that T lymphocyte played an important role in the anti-tumor activity. In conclusion, our results indicate that $18{\beta}$-GA has anti-tumor activity in HT-29 tumor-bearing mice, which may be associated with T cells.

• 약학회지
• /
• 제51권6호
• /
• pp.476-481
• /
• 2007

A polymorphic fungus, Candida albicans, causes various forms of infections such as disseminated candidiasis and vaginitis. Recent reports indicate that the fungus is a main etiological agent for the arthritis. In search of new sources for treatment of the fungal arthritis, we examined $18{\beta}$-glycyrrhetinic acid ($18{\beta}$-GA) against C. albicans-caused septic arthritis. The compound is isolated from Glycyrrhizae Radix that is known to have various immunomodulating activities and is one of the most popular herbal medicines. For induction of animal model of a septic arthritis, mice were given an emulsion form of C. albicans cell wall mixed with Complete Freund's Adjuvant (CFA) via footpad-injection. To determine prophylactic and therapeutic effects, the component was given to the animals before or after the induction of the arthritis, respectively. Data showed that intraperitoneal administration of $18{\beta}$-GA resulted in reduction of the inflammation, indicating the component had both prophylactic and therapeutic activities. For investigation of mechanism of the $18{\beta}$-GA, inhibitory effects on NO (nitiric oxide) and on T-lymphocyte proliferation were determined. Results demonstrated that $18{\beta}$-GA suppressed NO production from LPS (lipopolysaccharide)-treated macrophages and also inhibited proliferation of Con A (concanavalin A)activated T-cells. Taken together, $18{\beta}$-GA, a pentacyclic triterpene, has anti-arthritic activity against C. albicans-caused septic arthritis, possibly by blocking NO production and T-cell suppression.

• 대한본초학회지
• /
• 제31권6호
• /
• pp.73-81
• /
• 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.

• 한국응용약물학회:학술대회논문집
• /
• 한국응용약물학회 1998년도 Proceedings of UNESCO-internetwork Cooperative Regional Seminar and Workshop on Bioassay Guided Isolation of Bioactive Substances from Natural Products and Microbial Products
• /
• pp.125-125
• /
• 1998

Glycyrrhizin (18$\beta$-glycyrrhetic acid $\beta$-D-glucuronyl a-D-glucuronic acid, GL), a main component of liquore extract (Glycyrrhiza glabra), is ingested orally as a component in the oriental medicine. By human intestinal bacteria, glycyrrhizin (18$\beta$-glycyrrhetinic acid $\beta$-D-glucuronyl a-D-glucuronic acid, GL) was metabolized to glycyrrhetinic acid (GA): main pathway metabolizing GL to GA by glucuronidases of Bacteroides J-37 (Kim et al., 1997) and Eubacterium sp strain GLH (Akao et al., 1987) and minor pathway metabolizing GL to GA via 18$\beta$-glycyrrhetic acid D-glucuronic acid (GAMG) by $\beta$-glucuronidase of Streptococcus LJ-22 and glucuronidases of Bacteroides J-37 / E. coli. $\beta$-Glucuronidase from Streptococcus LJ-22 hydrolyzed GL to GAMG, not GA. $\beta$-Glucuronidase of Streptococcus LJ-22 hydrolyzed $\beta$-glucuronic acid conjugates of polysaccharides rather than aglycone-$\beta$-glucuronides Optimal pH of Streptococcus LJ-22 $\beta$-glucuronidase was 5-6 and its molecular weight was 250 kDaltons. Km for GL was 0.37mM.

• Archives of Pharmacal Research
• /
• 제23권2호
• /
• pp.172-173
• /
• 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.

• 한국독성학회:학술대회논문집
• /
• 한국독성학회 2002년도 Current Trends in Toxicological Sciences
• /
• pp.86-86
• /
• 2002

Glycyrrhizin, a triterpenoid saponin fraction of licorice, is reported to have anti-viral and anti-tumor activities and is metabolized to 18$\beta$-glycyrrhetinic acid (GA) in the intestine by intestinal bacteria. However, the mechanism underlying its effects is poorly understood.(omitted)

• Natural Product Sciences
• /
• 제8권2호
• /
• pp.35-43
• /
• 2002

Glycosides of herbal medicines, such as glycyrrhizin, ginsenosides, kalopanaxsaponins, rutin and ponicirin, were studied regarding their metabolic fates and pharmacological actions in relation to intestinal bacteria using germ-free, gnotobiotic and conventional animals. When glycyrrhizin (GL) was orally administered, $18{\beta}-glycyrrhetinic\;acid\;(GA)$, not GL, was detected in plasma and intestinal contents of gnotobiotic and conventional rats. However, GA could not be detected in germ-free rats. When GL was incubated with human intestinal bacteria, it was directly metabolized to GA (>95%) or via $18{\beta}-glycyrrhetinic\;acid-3-{\beta}-D-glucuronide$(>5%). Orally administered GL was effective in gnotobiotic and conventional rats for liver injury induced by carbon tetrachloride, but was not effective in germ-free rats. When ginseng saponins were orally administered to human beings, compound K in the plasma was detected, but the other protopanxadiol saponins were not detected. The compound K was active for tumor metastasis and allergy. When kalopanaxsaponins were incubated with human intestinal microflora, they were metabolized to kalopanaxsaponin A, kalopanaxsaponin I and hederagenin. These metabolites were active for rheumatoid arthritis and diabetic mellitus while the other kalopanxsaponins were not. When flavonoid glycosides were orally administered to animals, aglycones and/or phenolic acids were detected in the urine. The metabolic pathways proceeded by intestinal bacteria rather than by liver or blood enzymes. These metabolites, aglycones and phenolic acids, showed antitumor, antiinflammatory and antiplatelet aggregation activities. These findings suggest that glycosides of herbal medicines are prodrugs.

• 한국진공학회지
• /
• 제18권2호
• /
• pp.127-132
• /
• 2009

Sb에 기초한 응력 초격자 적외선검출소자의 구성 물질인 도핑하지 않은 기판 GaSb 결정과 GaSb/SI-GaAs 박막에 잔존하고 있는 진성결함 (intrinsic defect)을 비교 조사하였다. 상온 근처 (250 K)까지 광여기 발광 (PL)을 보이는 GaSb 결정에서의 발광 에너지의 온도의존성으로부터, 밴드갭 에너지에 관한 경험식인 Varshni 함수의 파라미터 ($E_o$, $\alpha$, $\beta$)를 결정하였다. GaAs 기판 위에 성장된 이종 GaSb 박막에서는 GaSb 주요 진성결함으로 알려져 있는 29 meV의 이온화 에너지를 가지는 위치반전 (antisite) Ga ([$Ga_{Sb}$]) 결함과 함께 위치반전 Sb ([$Sb_{Ga}$])와의 복합결함 ([$Ga_{Sb}-Sb_{Ga}$])과 관련된 것으로 분석된 732/711 meV의 한 쌍의 깊은준위 (deep level)가 관측되었다. PL의 온도 및 여기출력 의존성을 분석하여, Sb-rich상태에서 성장된 GaSb 박막에서는 잉여 Sb의 자발확산 (self-diffusion)에 의하여 치환된 위치전도 [$Ga_{Sb}$] 및 [$Sb_{Ga}$]가 결합하여 [$Ga_{Sb}-Sb_{Ga}$]의 깊은준위를 형성하는 것으로 해석되었다.