顽固性人巨细胞病毒

120:235475

Effect of glycyrrhizin, cyclosporin A, and tumor necrosis factor a on infection of U-937 and MRC-5 cells by human cytomegalovirus. 

Namazaki, Kei; Nagata, Nobuo; Sato, Toshiya; Chiba, Shunzo

(Sch.  Med., Sapporo Med. Univ., Sapporo 060, Japan). 

J. Leukocyte Biol., 55(1), 24-8 (English) 1994. 

Reactivation of latent or persistent human cytomegalovirus (HCMV) infection of monocytes or macrophages occurs under immunosuppressive conditions.  The authors investigated the effect of glycyrrhizin (GL), cyclosporin A (CsA), and tumor necrosis factor-a (TNF-a) on the viral DNA synthesis and antigen expression of HCMV in U-937 and MRC-5 cells.  Although GL inhibited the viral antigen expression of HCMV in human monocytic cell line U-937 and human embryonic lung cell line MRC-5 in the study, as detd. by flow cytometry and immunofluorescence assay, immediate early HCMV DNA was detected by the polymerase chain reaction.  CsA or TNF had no inhibitory effect on HCMV in U-937 or MRC-5 cells.  The HCMV infection model with U-937 or MRC-5 cells is of use for clarifying not only the mechanism of persistent infection but also the anti-HCMV effect of chem. agents.

 

非洲猪热病毒

117:316

Anionic compounds as inhibitors of African swine fever virus replication in Vero cells.

Garcia-Villalon, D.; Gil-Fernandez, C.

(Cent. Invest. Biol., Cons. Super.  Invest. Cient., Madrid 28006, Spain). 

Antiviral Chem. Chemother., 3(1), 9-14 (English) 1992. 

The anionic compds., aurintricarboxylic acid, Evans blue, glycyrrhizic acid, taurolithocholic acid, and fuchsin acid, have been tested for their capacity to inhibit the replication of African swine fever virus (ASFV) in Vero cells.  Aurintricarboxylic acid suppressed ASFV cytopathic effects at 5 mg/mL and emerged as the most efficacious inhibitor with a selectivity index (S.I.) of 400, followed by Evans blue with 40, Fuchsin acid with 20, taurolithocholic acid with 10, and glycyrrhizic acid with 5.  All the compds. inhibited the virus adsorption or penetration to the cells in some degree, but inhibition was also found when they were added after virus adsorption, indicating that other mechanism (or mechanisms) are involved in viral inhibition.

 

流行性出血热病毒

119:173663

Experimental study of inhibitory effect of the four traditional Chinese herb medicines on epidemic hemorrhagic fever virus. 

Zheng, Xuanhe; Tang, Xiaopeng; Su, Xianshi

(2^nd Affil. Hosp., Hunan Med. Univ., Changsha, Peop. Rep. China). 

Hunan Yike Daxue Xuebao, 18(2), 165-7 (Chinese) 1993. 

A lab. observation of inhibitory effect of artemether, glycyrrhizin, houttuynia and bupleura on epidemic hemorrhagic fever virus (EHFV) infection is reported.  The infection rates of the suckling mice treated with artemether and glycyrrhizin were much lower than that in the control group.  The distribution of EHFV in the suckling mice on houttuynia and bupleura was different from that in the control group.  It is indicated that artemether and glycyrrhizin can markedly prevent the EHFV infection in suckling mice.  Moreover, houttuynia and bupleura might inhibit EHFV infection to some extent.

 

白蛉热西西里病毒

128:212751

Inhibition of sandfly fever Sicilian virus (Phlebovirus) replication in vitro by antiviral compounds.

Crance, J. M.; Gratier, D.; Guimet, J.; Jouan, A.

(Unite de Virologie, Centre de Recherches du Service de Sante des Armees, La Tronche, Fr.). 

Res. Virol., 148(5), 353-365 (English) 1997

Sandfly fever Sicilian virus (SFSV) was used in our lab. to screen antiviral substances active toward viruses of the Bunyaviridae family.  Antiviral activity was estd. by the redn. of the cytopathic effect of SFSV on infected Vero cells.  Cytotoxicity was evaluated by detg. the inhibition of Trypan blue exclusion.  The specificity of action of each tested compd. was estd. by the selectivity index (CD50/ED50).  Selectivity indexes of human recombinant interferon-a (IFNa) (Roferon and Introna), iota-, kappa- and lambda- carrageenans, fucoidan and 6-azauridine were much higher than that of ribavirin, the only antiviral substance which has been previously investigated for its inhibitory effects on Phlebovirus infections.  Other compds. showed significant antiviral activity: glycyrrhizin, suramin sodium, dextran sulfate and pentosan polysulfate.  All these compds. caused a concn.-dependent redn. in the virus yield.  Ribavirin, 6-azauridine and IFNa have been shown to inhibit a late step of the virus replicative cycle, whereas glycyrrhizin and suramin sodium were active at an early step and the sulfated polysaccharides inhibited adsorption of SFSV on the cells.  The antiviral compds. selected in this study as specific inhibitors of in vitro replication of SFSV are promising candidates for the chemotherapy of hemorrhagic fevers caused by viruses of the Bunyaviridae family.  The combination of IFNa and ribavirin, which showed a synergistic antiviral effect, should be evaluated for the treatment of these infections.

 

鼠白血病病毒

134:41007

Glycyrrhizin improves the resistance of MAIDS mice to opportunistic infection of Candida albicans through the modulation of MAIDS-associated type 2 T cell responses.

Utsunomiya, Tokuichiro; Kobayashi, Makiko; Ito, Masahiko; Pollard, Richard B.; Suzuki, Fujio

(Division of Infectious Diseases, Department of Internal Medicine, The University of Texas Medical Branch, Galveston, TX 77555-0835, USA). 

Clin. Immunol. (Orlando, Fla.), 95(2), 145-155 (English) 2000

Compared with normal mice, MAIDS mice (mice infected with LP-BM5 murine leukemia virus) exhibited an increase up to 100 times greater in susceptibility to infection with Candida albicans.  The impaired resistance of MAIDS mice to the infection was recovered to levels obsd. in normal mice by the administration of glycyrrhizin (GR), an active component of licorice roots.  MAIDS mice inoculated with CD4+ T cells from GR-treated mice were also resistant to C. albicans infection.  Normal mice inoculated with CD4+ T helper type 2 cells (Th2 cells) from MAIDS mice were susceptible to C. albicans infection at the same levels shown in MAIDS mice.  The susceptibility of normal mice inoculated with type 2 T cells was reversible by (i) administration of GR and (ii) inoculation of CD4+ T cells from GR-treated mice and injection of a mixt. of mAbs targeted against type 2 cytokines (IL-4 and IL-10).  Type 2 cytokines were not detected in sera of MAIDS mice inoculated with CD4+ T cells from GR-treated mice, while they were present in sera of MAIDS mice treated with saline.  These results suggest that, by inducing CD4+ T cells which suppress type 2 cytokine prodn. by MAIDS-assocd. Th2 cells, GR improves the resistance of MAIDS mice to C. albicans infection.

 

马堡病毒 - 抑制病毒复制

126:271869

Inhibition of Marburg virus reproduction by glycyrrhizic acid and its derivatives.

Pokrovskii, A. G.; Belanov, E. F.; Volkov, G. N.; Plyasunova, O. A.; Tolstikov, G. A.

(Gos. Nauchn. Tsentr Virusol. Biotekhnol. “Vektor”, Novosibirsk, Russia). 

Dokl. Akad. Nauk, 344(5), 709-711 (Russian) 1995

The study demonstrated the inhibitory effect of glycyrrhizic acid and its derivs. glycyrrham and niglyzin (glycyrrhizic acid penta-O-nicotinate) on Marburg virus reprodn. in vitro.

 

抑制病毒生长 – 牛痘、单纯疱疹、鸡病毒性肺炎和脑脊椎病、水疱性口炎病毒

92:122494

Glycyrrhizic acid inhibits virus growth and inactivates virus particles.  Pompei, Raffaello; Flore, Ornella; Marccialis, Maria Antonietta; Pani, Alessandra; Loddo, Bernardo

(Inst. Microbiol. II, Univ. Cagliari, Cagliari, Italy). 

Nature (London), 281(5733), 689-90 (English) 1979. 

Glycyrrhizic acid (I)  [1405-86-3] (8 mM), a component of Glycyrrhiza glabra roots, completely inhibited growth and cytopathic effects of vaccinia, herpes simplex type 1, Newcastle disease, and vesicular stomatitis viruses in cultures of human aneuploid HEP2 cells.  I was also active on virus growth at 4 and 2, but not at 1 mM.  I had no effect on poliovirus type 1.  Uninfected cells incubated at 37?for 36 h with 8 mM I remained unaltered morphol. and in their ability to incorporate amino acids in acid and insol. form.  In 4-h-old cultures incubated in Eagle’s MEM 7% calf serum, 8 mM I decreased cell growth by 28% after 36 h.  I irreversibly inactivated herpes simplex virus type 1.  I possibly interacts with sensitive virus proteins at the virionic stage and later on when these proteins are synthesized in host cells.

 

抗病毒- 水泡性口炎病毒

111:17186

Inhibitory effect of glycyrrhizin in polypeptide phosphorylation by protein kinase of vesicular stomatitis virus.

Ohtsuki, Kenzo; Kanno, Shinichiro; Ishida, Nakao

(Sch. Hyg. Sci., Kitasato Univ., Sagamihara 228, Japan). 

Igaku no Ayumi, 148(2), 113-14 (Japanese) 1989. 

Inhibitory action of glycyrrhizin (I) in polypeptide phosphorylation was investigated in connection with its antiviral activity.  Solubilized protein kinase of vesicular stomatitis virus with 0.1% NP-40 was incubated with g-32P ATP in the presence of histone and 5 mM Mg2+ (or 2 mM Mn2+) for 10 min at 37?  Phosphorylated protein was sepd. by SDS-PAGE and developed by autoradiog.  The amt. of phosphorylated protein decreased in a dose-dependent manner and 50% by 20 mM I.  Similar inhibition was obsd. in casein phosphorylation by kinase P from HeLa S3 cell membrane.

 

人疱疹病毒

126:126539

Activity of glycyrrhizin and its diastereoisomers against two new human herpesviruses: HHV-6 and HHV-7.

Cermelli, C.; Portolani, M.; Colombari, B.; Castelli, M.; Baggio, G.; Bossa, R.; Galatulas, I.; Rossi, T.

(Department of Biomedical Sciences, University of Modena, Modena 41100, Italy). 

Phytother. Res., 10(Suppl.  1), S27-S28 (English) 1996

It has been demonstrated that glycyrrhizin inhibits the growth of different viruses in vitro, among which are some herpesviruses, of which HHV-6 and HHV-7 are the most recently discovered.  HHV-6 is the etiol. agent of exanthem subitum, but it may be responsible for more severe pathologies.  HHV-7 has been isolated from healthy subjects, patients with chronic fatigue syndrome and children with febrile illness but it has not been casually assocd. with any pathol.  The aim of our study was therefore to test the activity of glycyrrhizin and of 18a-and 18b-glycyrrhetinic acids against HHV-6 and HHV-7.  The antiviral activity of non-toxic concns. of each drug was assayed on lymphocytes infected with HHV-6 or HHV-7, the growth of the virus being monitored by immunofluorescence assay.  Results show that glycyrrhizin at 1.2 mM caused a 2.5-fold redn. of HHV-6 immunofluorescence pos. cells.  A 10-fold redn. was obtained using glycyrrhizin at 3.6 mM, but at this concn. it also had a few cytotoxic effects.  18a- And 18b-glycyrrhetinic acids seem to have a stimulating effect on HHV-6 growth, with a two-fold increase in pos. cells.  The three drugs did not show any activity on HHV-7 growth.

 

单纯疱疹脑炎病毒

136:144686

Glycyrrhizin increases survival of mice with herpes simplex encephalitis.

Sekizawa, T.; Yanagi, K.; Itoyama, Y.

(Department of Neurology, Tohoku University School of Medicine, Sendai, Japan). 

The authors examd. the effect of glycyrrhizin (GR), a component of licorice root ext., on herpetic encephalitis that was inflicted on mice by inoculation of herpes simplex virus 1 (HSV-1) onto their cornea.  I.p.  administration of GR to mice suffering from herpetic encephalitis increased their survival rate in av. about 2.5 times (from 37.5-29.0% to 81.8-83.3%; mean values from 2 expts.) while it reduced HSV-1 replication in the brain to 45.6% of the control.  These results demonstrate a stimulative effect of GR on the mouse defense system(s) against HSV-1 infection.

 

单纯疱疹病毒

122:177787

Glycyrrhizin (20b-carboxy-11-oxo-30-norolean-12-en-3b-yl-2-O-b-D-glucopyranuronosyl-a-D-glucopyranosiduronic acid) improves the resistance of thermally injured mice to opportunistic infection of herpes simplex virus type 1.

Utsunomiya, Tokuichiro; Kobayashi, Makiko; Herndon, David N.;

Pollard, Richard B.; Suzuki, Fujio

(Department of Internal Medicine, University of Texas Medical Branch and, Galveston, TX 77555, USA).

Immunol. Lett., 44(1), 59-66 (English) 1995.

The effect of glycyrrhizin (GR) on the resistance of thermally injured mice to opportunistic herpes simplex virus type 1 (HSV) infection was investigated.  The authors have previously reported that the susceptibility of thermally injured mice or normal mice inoculated with T6S cells (a clone of burn-assocd. CD8+ CD11b+ TCRg/d+ type-2 suppressor T cells), to HSV infection was about 100 times greater than it was in normal mice.  When thermally injured mice were treated i.p.  with a 10 mg/kg dose of GR 2 and 4 days after infection with HSV, the resistance of these mice to HSV was improved to levels obsd. in normal mice.  The adoptive transfer of splenic mononuclear cells (MNC) from normal mice treated with GR (GR-MNC) to thermally injured mice (recipients) resulted in the improved resistance of recipients to HSV infection.  Normal mice inoculated with T6S cells and exposed to HSV had an 80% mortality rate, when given GR-MNC they had a 95% survival rate.  The suppressor cell activity of T6S cells was clearly counteracted by GR-MNC in vitro in a mixed lymphocyte-tumor cell reaction.  The type of cells responsible for anti-suppressor cells in GR-MNC was shown to be a CD4+ CD28+ TCRa/b+ Vicia villosa lectin-adherent T cell.  These results suggest that GR may reverse the increased susceptibility of thermally injured mice to HSV infection through the induction of CD4+ contrasuppressor T cells.

 

抗病毒 – 带状疱疹病毒

106:131309

Antiviral activity of glycyrrhizin against varicella-zoster virus in vitro.

Baba, Masanori; Shigeta, Shiro

(Dep. Bacteriol., Fukushima Med.

Coll., Fukushima 960, Japan). 

Antiviral Res., 7(2), 99-107 (English) 1987. 

One of the plant exts., glycyrrhizin  (GL)  [1405-86-3] was investigated for its antiviral action on varicella-zoster virus (VZV) in vitro.  When human embryonic fibroblast (HEF) cells were treated with GL after inoculation of virus (post-treatment), the av. 50%-ID (ID50) for five VZY strains was 0.71 mM, and the selectivity index (ratio of ID50 for host-cell DNA synthesis to ID50 for VZV replication) was 30.  GL was also effective against VZV replication when HEF cells were treated 24 h before the inoculation (pretreatment).  Furthermore, at a concn. of 2.4 mM GL inactivated more than 99% of virus particles within 30 min at 37?  In combination with other anti-herpes drugs (acyclovir [59277-89-3], adenine arabinoside  [5536-17-4], bromovinyldeoxyuridine  [69304-47-8], and phosphonoformate [4428-95-9]) or human native beta-interferon, GL had an additive or slightly synergistic effect on VZV replication.  The mechanism of anti-VZV action is still unclear.  It is postulated that GL inhibits the penetration, uncoating or release of virus particles.

 

疱疹病毒

136:48007

Enhancement of anti-herpetic activity of glycyrrhizic acid by physiological proteins.

Lampis, G.; Deidda, D.; Pinza, M.; Pompei, R.

(Cattedra di Microbiologia Applicata, Universita di Cagliari, Cagliari, Italy). 

Antiviral Chemistry & Chemotherapy, 12(2), 125-131 (English) 2001

Some enzymes present in biol. fluids, such as lysozyme (LYS) and lactoferrin (LAC), are known to possess antibacterial and antiviral activity, against herpesviruses in particular.  It will be shown in this paper that their combination with a natural triterpene, namely glycyrrhizic acid (GLA), gives significant results in enhancing the antagonistic activity on HSV1 in in vitro assays.  Data elaboration was carried out by calcn. of the FIC index (fractional inhibitory concn.) for each combination of the three compds. and by a three-dimensional evaluation of the inhibiting combinatory effects, which indicated the percentage of the synergistic action.  A FIC index equal to or below 0.5 demonstrated a significant synergistic effect between two substances.  Considering each single compd., the 50% inhibiting doses on viral replication (ID50) were 252 ?53 mg/mL for LAC, 497 ?165 mg/mL for LYS and 740 ?125 mg/mL for GLA.  The combination of LAC and GLA showed a clear synergistic effect, with a FIC index of 0.08 and a potentiating activity which, for some doses, was up to 1.5 log10 of difference (from about 5.5 X 106 to 105 pfu/mL).  The combinations of GLA and LYS, and LYS and LAC showed a less significant synergistic activity.  These findings led to the conclusion that some physiol.  proteins, even at concns. usually present in some body fluids, may enhance the anti-herpetic activity of a natural compd. such as GLA.

 

 

流感病毒

100:61442

Glycyrrhizic acid inhibits influenza virus growth in embryonated eggs.

Pompei, R.; Paghi, L.; Ingianni, A.; Uccheddu, P.

(Ist. Microbiol., Univ.  Cagliari, Cagliari, Italy).  Microbiologica (Bologna), 6(3), 247-50 (English) 1983. 

Glycyrrhizic acid  [1405-86-3], at concns. well tolerated by the cells in monolayer cultures, decreased the recovery of hemagglutinins from influenza virus-infected embryonated hen eggs.  Since the drug had no effect on viral viability and did not impair the hemagglutinating activity of the virions, the growth of the viruses in the embryo tissues might have been mainly affected.  Late viral replication steps, rather than the early ones, appeared to be involved in the inhibitory effect of glycyrrhizic acid.

 

流感病毒

123:218387

Influenza therapeutics containing glycyrrhizin.

Suzuki, Fujio; Horaado, Birudo Richaado; Kobayashi, Makiko;

Utsunomya, Tokuichiro; Utsunomya, Kyozo

(Minophagen Pharma Co, Japan). 

Jpn. Kokai Tokkyo Koho JP 07188032 A2 25 Jul 1995 Heisei, 9 pp. (Japan). 

The therapeutics contain glycyrrhizin (I) and /or its pharmacol.  acceptable salts as active ingredients.  Mice i.p. treated with I at 10 mg/kg 1 day before and 1 and 4 days after transnasal inoculation with influenza A2(H2N2) virus at the amt. of 10 LD50 showed survival rate 100%, vs. 0% for untreated controls.  A tabelt contg. I was formulated.

 

流感病毒

126:246520

Glycyrrhizin, an active component of licorice roots, reduces morbidity and mortality of mice infected with lethal doses of influenza virus. 

Utsunomiya, Tokuichiro; Kobayashi, Makiko; Pollard, Richard B.;

Suzuki, Fujio

(Dep.Internal Med., Univ. Texas Medical Branch, Galveston, TX 77555, USA). 

Antimicrob. Agents Chemother., 41(3), 551-556 (English) 1997

The antiviral effect of glycyrrhizin (GR), an active component of licorice roots, was investigated in mice infected with influenza virus A2 (H2N2).  When mice that had been exposed to 10 50% LDs of the virus were treated i.p. with 10 mg of GR per kg of body wt. 1 day before infection and 1 and 4 days postinfection, all of the mice survived over the 21-day exptl. period.  At the end of this period, the mean survival time (in days) for control mice treated with saline was 10.5 days, and there were no survivors.  The grade of pulmonary consolidations and the virus titers in the lung tissues of infected mice treated with GR were significantly lower than those in the lung tissues of infected mice treated with saline.  GR did not show any effects on the viability or replication of influenza virus A2 in vitro.  When splenic T cells from GR-treated mice were adoptively transferred to mice exposed to influenza virus, 100% of the recipients survived, compared to 0% survival for recipient mice inoculated with naive T cells or splenic B cells and macrophages from GR-treated mice.  In addn., the antiviral activities of GR on influenza virus infection in mice were not demonstrated when it was administered to infected mice in combination with anti-gamma interferon (anti-IFN-g) monoclonal antibody.  These results suggest that GR may protect mice exposed to a lethal amt. of influenza virus through the stimulation of IFN-g prodn. by T cells, because T cells have been shown to be producer cells of IFN-g stimulated with the compd.

 

肝炎病毒

134:95268

Glycyrrhizin inhibits the lytic pathway of complement - possible mechanism of its anti-inflammatory effect on liver cells in viral hepatitis. 

Fujisawa, Yumiko; Sakamoto, Motoko; Matsushita, Misao; Fujita, Teizo; Nishioka, Kusuya

(Department of Health and Nutrition, School of Home Economics, Wayo Women’s University, Chiba 272-8533, Japan). 

Microbiol. Immunol., 44(9), 799-804 (English) 2000

Glycyrrhizin, an aq. ext. of licorice root, has anti-inflammatory activity and has been used for the treatment of chronic viral hepatitis.  In the present study we describe the mechanism by which glycyrrhizin inhibits complement.  Glycyrrhizin inhibited the cytolytic activity of complement via the activation of both the classical and alternative pathways, while it had no effect on immune adherence, suggesting that it blocks C5 or a later stage of the complement cascade.  Further anal. revealed that glycyrrhizin inhibits the lytic pathway in which the membrane attack complex (MAC) is formed.  This mechanism suggests that glycyrrhizin may prevent tissue injury caused by MAC not only in chronic hepatitis but in many autoimmune and inflammatory diseases.

 

肝炎 – 亚急性肝炎

136:288596

Treatment of subacute hepatitis with lamivudine and intravenous glycyrrhizin: A pilot study.

Tandon, Anurag; Tandon, B. N.; Bhujwala, R. A.

(Pushpawati Singhania Research Institute, New Delhi 110017, India). 

Hepatology Research, 20(1), 1-8 (English) 2001

Subacute hepatitis is a common and distinct clinicopathol. entity due to Hepatitis B and E viruses in India.  Lamivudine has been established as a safe and effective antiviral agent for the treatment of chronic HBV hepatitis.  This drug was administered orally along with i.v. (I/V) Glycyrrhizin, an immunomodulator drug, in an open pilot trial to assess its efficacy in the treatment of subacute hepatitis.  The results establish the safety and efficacy of Lamivudine in combination with I.V.  Glycyrrhizin in subacute Hepatitis.

 

抑制甲型肝炎病毒复制

113:144908

Inhibition of hepatitis A virus replication in vitro by antiviral compounds.

Crance, J. M.; Biziagos, E.; Passagot, J.; Van Cuyck-Gandre, H.; Deloince, R.

(Unite Biol. Mol., Cent. Rech. Serv. Sante Armees, La Tronche 38702, Fr.). 

J. Med. Virol., 31(2), 155-60 (English) 1990. 

Forty antiviral compds. were screened for inhibitory effect on hepatitis A virus (HAV) antigen expression in the human hepatoma cell line PLC/PRF/5.  Ribavirin, amantadine, glycyrrhizin, and pyrazofurin were selected in this screening test and were studied further.  The selectivity indexes of these four compds., calcd. as the ratio of 50% cytotoxic dose (detd. by the trypan blue exclusion and by inhibition of [3H]leucine incorporation) to the 50% ED (detd. by the viral antigen expression), were 4.6 and 3.0 with ribavirin, 5.3 and 5.9 with amantadine, 15.2 and 16.9 with glycyrrhizin, and 45.4 and 74.6 with pyrazofurin.  All four compds. resulted in concn.-dependent redns. of HAV antigen expression and HAV infectivity.  Ribavirin, amantadine, pyrazofurin, and glycyrrhizin emerged, from the present study, as promising candidates for chemotherapy of acute hepatitis A.

 

抗乙肝

125:104320

Therapeutic basis of glycyrrhizin on chronic hepatitis B. 

Sato, Hitoshi; Goto, Wakana; Yamamura, Jun-ichi; Kurokawa, Masahiko; Kageyama, Seiji; Takahara, Terumi; Watanabe, Akiharu;

Shiraki, Kimiyasu

(Department of Virology, Toyama Medical and Pharmaceutical University, Toyama, Japan). 

Antiviral Res., 30(2,3), 171-177 (English) 1996. 

Glycyrrhizin, a major component of a herb (licorice), has been i.v. used for the treatment of chronic hepatitis B in Japan and improves liver function with occasional complete recovery from hepatitis.  This substance modifies the intracellular transport and suppresses sialylation of hepatitis B virus (HBV) surface antigen (HBsAg) in vitro.  This study was designed to clarify the pharmacol. basis for its effectiveness.  The structure-bioactivity relation of glycyrrhizin, glycyrrhetic acid 3-O-monoglucuronide and glycyrrhetic acid was detd., and glycyrrhetic acid was found to be the most active of them.  The amts. of three substances bound to the liver were evaluated in guinea pigs after i.v. administration of glycyrrhizin.  Glycyrrhizin and glycyrrhetic acid 3-O-monoglucuronide were detected at concns. of 31.8-1.3 mg/g of liver, but glycyrrhetic acid was not detected.  When glycyrrhizin attained these concns. in the cellular fraction of the PLC/PRF/5 cell culture, it suppressed the secretion of HBsAg as reported previously.  These results indicated that glycyrrhizin administered i.v. might bind to hepatocytes at the concn. at which glycyrrhizin could modify the expression of HBV-related antigens on the hepatocytes and suppress sialylation of HBsAg.

 

乙肝病毒

117:82950

Antiviral effect of glycyrrhizin on duck hepatitis B virus.  Effect in duck hepatocyte primary culture.

Tamura, Tohru

(Sch. Med., Hiroshima Univ., Hiroshima 734, Japan). 

Hiroshima Daigaku Igaku Zasshi, 39(6), 605-15 (Japanese) 1991. 

The cultured duck hepatocytes were inoculated with duck hepatitis B virus (DHBV) over 24 h.  Addn. of glycyrrhizin (GL) to the culture medium for 9 days from the beginning of the inoculation showed antiviral effect on DHBV (IC50 0.45 mg/mL) without cytotoxicity against the hepatocytes, but no antiviral effect when GL was added at the end of inoculation.  GL suppressed the release of DHBV-DNA into the medium from the DHBV-inoculated hepatocyte, whereas GL had no inhibitory effect on DHBV-DNA polymerase activity.  These results suggest that GL has inhibitory effects on the absorption, penetration, and release of virus particles, but has no inhibitory effect on virus replication in the hepatocytes nor directly inactivating effect on the virus particles.

 

乙肝病毒

116:120453

Antiviral effect of glycyrrhizin against duck hepatitis B virus in duck hepatocyte primary culture.

Tamura, Tohru; Amano, Hajime; Kohno, Hiroshi; Kawaguchi, Minoru; Kamiyasu, Masaya; Miura, Toshio; Kitamoto, Mikiya; Itoh, Hiroyuki; Komatsu, Kouichi; et al.

(Sch. Med., Hiroshima Univ., Hiroshima, Japan). 

Kanzo, 32(11), 990-6 (Japanese) 1991. 

The antiviral effect of glycyrrhizin (GL) against duck hepatitis B virus (DHBV), belonging to the same Hapadna virus family as human hepatitis B virus (HBV), was studied using duck hepatocyte primary culture.  GL showed an antiviral effect against DHBV at a concn. of 1.0 mg/mL without cytotoxicity against the hepatocytes.  The 50% ID (ID50) was 0.46 mg/mL.  With regard to the mechanism of the antiviral effect, it is considered that GL has inhibitory effects on the absorption, penetration and release of virus particles but does not inhibit the virus replication in the hepatocytes nor directly inactivates the virus particles.  The antiviral effect of GL against DHBV proved to be weak at a concn.  of 0.25 mg/mL.  Considering that this concn. is higher than the clin.  dose, it is suggested that the anti-HBV effect of GL is very weak at the clin. dose.

 

丙肝病毒

125:316275

Effectiveness of glycyrrhizin for oral lichen planus in patients with chronic HCV infection.

Nagao, Yumiko; Sata, Michio; Suzuki, Hiroshi; Tanikawa, Kyuichi; Itoh, Kyogo; Kameyama, Tadamitsu

(School Medicine, Kurume University, Kurume 830, Japan). 

J. Gastroenterol., 31(5), 691-695 (English) 1996. 

Oral lichen planus (OLP), an intractable inflammatory disease characterized by a band-like lymphocytic invasion under the oral mucosa, is frequently assocd. with hepatitis C virus (HCV) infection.  We investigated the effects of glycyrrhizin, which is used to treat chronic liver dysfunction, in nine patients with OLP who were pos. for HCV antibody and HCV RNA.  A control group, eight patients with OLP who were also pos. for HCV antibody and HCV RNA, was given only dental cleaning.  Glycyrrhizin (GL) was given i.v., at a dose of 40 mL (0.2% soln.) daily, for 4 consecutive weeks.  Six (66.7%) of the nine patients given GL improved clin. (vs. non-GL group), suggesting that GL is useful in treating OLP.

 

抗丙肝

135:352399

Glycyrrhizin-induced reduction of ALT in European patients with chronic hepatitis C.

Van Rossum, Tekla G. J.; Vulto, Arnold G.; Hop, Wim C. J.; Schalm, Solko W.

(Departments of Hepatogastroenterology and Hospital Pharmacy, University Hospital Rotterdam, Rotterdam, Neth.).

Am. J.  Gastroenterol., 96(8), 2432-2437 (English) 2001

In Japan, ALT normalization induced by longterm i.v. glycyrrhizin treatment reportedly reduces the progression of liver disease to hepatocellular carcinoma in chronic hepatitis C patients.  The aim of this study was to evaluate the short-term (4-wk) feasibility and efficacy on serum ALT of three or six times per wk i.v. glycyrrhizin therapy in European patients.  Patients with chronic hepatitis C, nonresponders, or unlikely to respond (genotype 1/cirrhosis) to interferon therapy were included in this study.  Medication was administered i.v. three or six times per wk for 4 wk; follow-up also lasted 4 wk.  Sixty-nine out of 72 treatment courses were completed according to protocol.  There were no significant changes in ALT levels within the placebo group (n = 13).  The mean percentage ALT decrease from baseline at the end of treatment was 26% and 47% for the three times per wk and six times per wk treatment group, resp. (both p < 0.001 vs placebo).  At the end of active treatment, 10% (four of 41) and 20% (three of 15) of the patients reached normal ALT levels for the three times per wk and six times per wk treatment group, resp.  The ALT lowering effect disappeared after cessation of treatment.  No major side effects were obsd.  It appeared feasible to treat European outpatients with chronic hepatitis C three or six times per wk with i.v. glycyrrhizin.  Glycyrrhizin treatment induces a significant ALT decrease in patients with chronic hepatitis C.  Six times per wk treatment appears more effective than three times per wk.

 

抗丙肝

135:352388

“Pseudo-aldosteronism” induced by intravenous glycyrrhizin treatment of chronic hepatitis C patients.

Van Rossum, Tekla Gj; De Jong, Frank H.; Hop, Wim Cj; Boomsma, Frans; Schalm, Solko W.

(Department of Hepatogastroenterology, Erasmus University Hospital Rotterdam, Rotterdam 3000 CA, Neth.). 

J. Gastroenterol. Hepatol., 16(7), 789-795 (English) 2001

Treatment with i.v. glycyrrhizin reduces the progression of liver disease caused by chronic hepatitis C (HCV) infection.  Glycyrrhetinic acid, a metabolite of glycyrrhizin, inhibits the renal conversion of cortisol to cortisone by inhibiting the enzyme 11b-hydroxysteroid-dehydrogenase in the kidney.  The resulting excess of cortisol subsequently stimulates the mineralocorticoid receptor, leading to pseudo-aldosteronism with hypertension, hypokalemia and eventually renin and aldosterone suppression.  The aim of this study was to evaluate the occurrence of pseudo-aldosteronism after treatment of chronic hepatitis C (HCV) patients with increasing doses of i.v. glycyrrhizin.  Forty-four HCV patients with chronic hepatitis or compensated cirrhosis were treated with i.v. glycyrrhizin 6 ?200 mg/wk, 3 ?240 mg/wk or 3 ?0 mg/wk (placebo) for 4 wk.  In all patients, body wt., blood pressure and plasma concns. of sodium, potassium, cortisol, DHEA-S (dehydroepiandrosterone sulfate), renin and aldosterone were measured before, and at 0 and 4 wk after treatment.  Within the placebo group, no significant changes were obsd.  Within the 1200 mg group systolic blood pressure was significantly higher at the end of treatment, while aldosterone was significantly lower; at the end of the follow-up period these values had returned to baseline.  The changes from baseline in systolic and diastolic blood pressure at the end of treatment were significantly higher in the 1200 mg group compared to the placebo group.  The changes in aldosterone and potassium concns. at the end of treatment increased with increasing dosage, although not significantly.  Hepatitis C virus patients with chronic hepatitis or compensated cirrhosis show minor reversible symptoms of pseudo-aldosteronism after treatment with 1200 mg glycyrrhizin weekly for 4 wk.

 

抗丙肝病毒

132:117154

Pharmacokinetics of intravenous glycyrrhizin after single and multiple doses in patients with chronic hepatitis C infection. 

Van Rossum, Tekla G. J.; Vulto, Arnold G.; Hop, Wim C. J.; Schalm, Solko W.

(Department of Hepatogastroenterology, Erasmus University Hospital Rotterdam, Rotterdam, Neth.). 

Clin. Ther., 21(12), 2080-2090 (English) 1999

I.v. glycyrrhizin has been used in Japan for the treatment of chronic hepatitis for >20 yr, although only a few reports of its pharmacokinetic profile after multiple i.v. doses in small nos. of Japanese patients have been published.  The present study compared these Japanese data against the pharmacokinetic characteristics of glycyrrhizin after single and multiple i.v. doses in 35 European patients with chronic hepatitis C infection.  We administered 80, 160, or 240 mg glycyrrhizin 3 times/wk or 200 mg glycyrrhizin 6 times/wk for 4 wk.  Twenty-four-hour pharmacokinetic assessments were performed on day 1 and on or around day 14.  Glycyrrhizin levels were detd. by high-performance liq.  chromatog.  The mean (±SD) vol. of distribution at steady state on day 1 in the 80-, 160-, 200-, and 240-mg groups were 67 ?11, 62 ?13, 54 ?7, and 66 ?8 mL/kg, resp.  The resp. terminal elimination half-lives on day 1 were 7.7 ?2.8, 10.1 ?1.4, 9.0 ?2.3, and 8.6 ?2.1 h.  The area under the curve (AUC) increased linearly with doses ?00 mg (r = 0.67;

P < 0.001).  No significant differences between day 1 and day 14 were found in any dose group, with the exception of AUC in the 200-mg group, which was significantly higher on day 14 compared with day 1 (P = 0.03).  Comparing the European and Japanese data, the mean (?  SD) AUC was 289 ?244 mg/h per mL for the former and 402 ?372 mg/h per mL for the latter; the half-life was 8.2 ?2.6 vs. 8.8 ?9.0 h; and the total clearance was 7.6 ?3.6 vs. 8.5 ?5.7 mL/h per kg.  Thus our pharmacokinetic data are comparable to those from Japan.  Glycyrrhizin’s pharmacokinetics are linear up to 200 mg.  Drug accumulation is seen after 2 wk of treatment with 200 mg administered 6 times/wk.

 

抗丙肝

132:102462

Intravenous glycyrrhizin for the treatment of chronic hepatitis C: A double-blind, randomized, placebo-controlled phase I/II trial. 

Van Rossum, Tekla G. J.; Vulto, Arnold G.; Hop, Wim C. J.; Brouwer, Johannes T.; Niesters, Hubert G. M.; Schalm, Solko W.

(Department of Hepatogastroenterology, Erasmus Medical Center, Rotterdam, Neth.). 

J. Gastroenterol. Hepatol., 14(11), 1093-1099 (English) 1999

In Japan, glycyrrhizin therapy is widely used for chronic hepatitis C and reportedly reduces the progression of liver disease to hepatocellular carcinoma.  The aims of this study were to evaluate the effect of glycyrrhizin on serum alanine aminotransferase (ALT), hepatitis C virus (HCV)-RNA and its safety in European patients.  Methods: Fifty-seven patients with chronic hepatitis C, non-responders or unlikely to respond (genotype 1/cirrhosis) to interferon therapy, were randomized to one of the four dose groups: 240, 160 or 80 mg glycyrrhizin or placebo (0 mg glycyrrhizin).  Medication was administered i.v. thrice weekly for 4 wk; follow up also lasted for 4 wk.  Results: Within 2 days of start of therapy, serum ALT had dropped 15% below baseline in the three dosage groups (P<0.02).  The mean ALT decrease at the end of active treatment was 26%, significantly higher than the placebo group (6%).  A clear dose-response effect was not obsd. (29, 26, 23% ALT decrease for 240, 160 and 80 mg, resp.).  Normalization of ALT at the end of treatment occurred in 10% (four of 41).  The effect on ALT disappeared after cessation of therapy.  During treatment, viral clearance was not obsd.: the mean decrease in plasma HCV-RNA after active treatment was 4.1?06 genome equiv./mL (95% confidence interval, 0-8.2?06; P>0.1).  No major side-effects were noted.  None of the patients withdrew from the study because of intolerance.  Conclusions: Glycyrrhizin up to 240 mg, thrice weekly, lowers serum ALT during treatment, but has no effect on HCV-RNA levels.  The drug appears to be safe and is well tolerated.  In view of the reported long-term effect of glycyrrhizin, further controlled investigation of the Japanese mode of administration (six times weekly) for induction appears of interest.

 

抗丙肝病毒

133:246833

Combined ursodeoxycholic acid and glycyrrhizin therapy for chronic hepatitis C virus infection: A randomized controlled trial in 170 patients. 

Tsubota, Akihito; Kumada, Hiromitsu; Arase, Yasuji; Chayama, Kazuaki; Saitoh, Satoshi; Ikeda, Kenji; Kobayashi, Masahiro; Suzuki, Yoshiyuki; Murashima, Naoya

(Department of Gastroenterology, Toranomon Hospital, Tokyo 105-0001, Japan). 

Eur. J. Gastroenterol.  Hepatol., 11(10), 1077-1083 (English) 1999

To assess the efficacy and safety of combination therapy using ursodeoxycholic acid with glycyrrhizin for chronic hepatitis C virus infection, we conducted a prospective randomized controlled trial of glycyrrhizin (group G) compared with glycyrrhizin plus ursodeoxycholic acid (group G+U) in 170 patients.  All patients had elevated serum aminotransferase levels over 6 mo before entry into the trial.  Glycyrrhizin was administered to both groups for 24 wk, and in group G+U, ursodeoxycholic acid (600 mg/day) was administered orally as well.  Serum aspartate transaminase and alanine transaminase concns. significantly decreased during treatment in both groups, but serum gamma-glutamyl transpeptidase concns. fell significantly only in group G+U.  Concns. of all three enzymes fell significantly more in group G+U than in group G, and had normalized in more cases when the trial ended at 24 wk.  However, levels of HCV viremia did not change during the trial in either group.  Multiple regression anal. linked only the treatment regimen, not HCV-related factors or liver histol., to the degree of serum enzyme redn.  No adverse effects were noted in either group.  The combined therapy with ursodeoxycholic acid and glycyrrhizin is safe and effective in improving liver-specific enzyme abnormalities, and may be an alternative to interferon in chronic hepatitis C virus infection, esp. for interferon-resistant or unstable patients.

 

丙肝病毒

126:325131

The long term efficacy of glycyrrhizin in chronic hepatitis C patients.

Arase, Yasuji; Ikeda, Kenji; Murashima, Naoya; Chayama, Kazuaki; Tsubota, Akihito; Koida, Isao; Suzuki, Yoshiyuki; Saitoh, Satoshi; Kobayashi, Masahiro; Kumada, Hiromitsu

(Department of Gastroenterology, Tonanomon Hospital, Tokyo, Japan). 

Cancer (N. Y.), 79(8), 1494-1500 (English) 1997

Hepatocellular carcinoma (HCC) occurs in patients with hepatitis C virus-RNA pos. chronic liver disease.  It is important to prevent HCC with drug administration.  A retrospective study was undertaken to evaluate the long term preventive effect of Stronger Neo-Minophagen C (SNMC) on HCC development.  SNMC is a Japanese medicine that is commonly administered to patients with chronic hepatitis C to improve the serum alanine aminotransferase (ALT) level.  Of 453 patients diagnosed with chronic hepatitis C retrospectively in the study hospital between Jan. 1979 and Apr. 1984, 84 patients (Group A) had been treated with SNMC; SNMC was given at a dose of 100 mL daily for 8 wk, then 2-7 times a week for 2-16 yr (median, 10.1 yr).  Another group of 109 patients (Group B) could not be treated with SNMC or interferon for a long period of time (median, 9.2 yr) and were given other herbal medicine (such as vitamin K).  The patients were retrospectively monitored, and the cumulative incidence of HCC and risk factors for HCC were examd.  The 10^th-year rates of cumulative HCC incidence for Groups A and B were 7% and 12%, resp., and the 15^th-year rates were 12% and 25%.  By Cox regression anal., the relative risk of HCC incidence in patients not treated with SNMC (Group B) was 2.49 compared with that of patients treated with SNMC (Group A).  In this study, long term administration of SNMC in the treatment of chronic hepatitis C was effective in preventing liver carcinogenesis.

 

 

抗爱滋病毒

117:157629

AIDS virus inhibitors containing heteroannular glycyrrhizin. 

Hirabayashi, Kazuhiro; Mori, Takeo; Matsumoto, Hiroatsu; Iwata, Susumu; Shibata, Shoji; Shigeta, Shiro; Ito, Masahiko

(Goshi Kaisha Minophagen Seiyaku Honpo, Japan). 

Jpn. Kokai Tokkyo Koho JP 04077428 A2 11 Mar 1992 Heisei, 6 pp. (Japan). 

AIDS virus inhibitors contain heteroannular glycyrrhizin (I) and its medically acceptable salts as active ingredients.  I does not cause pseudoaldosteronism unlike glycyrrhizin (no data).  I (prepd. via 11b-hydroglycyrrhizin from glycyrrhizin) at 0.16-1.24 mM inhibited growth of human immunodeficiency virus in MT-4 cell system, resulting in ?~80% survival of the infected cell.  LD50 of I was 333-358 mg/kg i.v.  in mice.  Tablets were formulated contg. I 400, CaCO3 200, cryst.  cellulose 300, talc 10, and lactose 590 g.

 

抗爱滋病毒

119:130976

Anti-HIV activity of b-glycyrrhizic acid.

Plyasunova, O. A.; Egoricheva, I. N.; Fedyuk, N. V.;Pokrovsky,A. G.; Baltina, L. A.; Murinov, Yu. I.; Tolstikov, G. A.

(NII Mol. Biol., Koltsovo, Russia). 

Vopr. Virusol., 37(5-6), 235-8 (Russian) 1992. 

The anti-HIV activity of b-glycyrrhizic acid (GA) and various derivs. was studied using various strains of HIV-1 and HIV-2 in primary infected lymphoblastoid cells MT-4 and monocyte cell line U-973 chronically infected with HIV-1 and contg. provirus (GKV 4005).  Beta-glycyrrhizic acid and its derivs. were shown to effectively inhibit HIV-1 reprodn. in MT-4 cells.  The antiviral effect of b-GA sodium salt exceeded that of AZT in cells GKV 4005.  The selective indexes for some GA salts were evaluated, namely: 53 for 1NH4 salt of GA, 6.7 for 1K-2Li salt of GA;

4.45 for Ga.  The mechanism of Ga action is discussed.

 

 

抗爱滋病毒

107:211581

A new anti-human immuno-deficiency virus substance, glycyrrhizin sulfate: endowment of glycyrrhizin with reverse transcriptase-inhibitory activity by chemical modification.

Nakashima, Hideki; Matsui, Toshio; Yoshida, Osamu; Isowa, Yoshikazu; Kido, Yasuji; Motoki, Yoshinobu; Ito, Masahiko; Shigeta, Shiro; Mori, Takeo; Yamamoto, Naoki

(Sch. Med., Yamaguchi Univ., Ube 755, Japan). 

Jpn. J. Cancer Res. (GANN), 78(8), 767-71 (English) 1987. 

Glycyrrhizin sulfate (GLS) was synthesized and investigated for antiviral effect on the human immunodeficiency virus (HIV) in vitro in comparison with the parental anti-HIV compd. glycyrrhizin (GL).  In MT-4 cells after HIV infection, the virus-induced cytopathic effect and the expression of viral antigens were inhibited by 0.25 mg/mL (0.184 mM) of GLS.  Moreover, GLS completely inhibited HIV-induced plaque formation in MT-4 cells at a concn. of 1 mg/mL (736 mM), the 50% ID being 0.055 mg/mL (40 mM).  GLS was an efficient inhibitor of reverse transcriptase.  The effect of GLS was 4-fold stronger than that of GL in molar terms.

 

抗爱滋病毒

107:89374

Inhibitory effect of glycyrrhizin on the cytopathic activity of human immune deficiency  virus.

Ito, Masahiko; Nakashima, Hideki; Baba, Masanori; Shigeta, Shiro; Yamamoto, Naoki

(Dep. Bacteriol., Fukushima Med. Coll., Fukushima 960, Japan).  Igaku no Ayumi, 141(7), 427-8 (Japanese) 1987. 

Glycyrrhizin (GL) completely inhibited human immunodeficiency virus (HIV)-induced plaque formation in MT-4 cells at the conc. of 0.5 mg/mL.  The dose of GL inhibiting 50% plaque formation was 0.125 mg/mL.  This compd. also completely inhibited the HIV-induced cytoplasmic effect and virus-specific antigen expression in MT-4 cells, and giant-cell formation in HIV-infected Molt-4 cells.  However, GL had no effect on the reverse transcriptase of HIV.

 

抗爱滋病毒

107:51432

Inhibitory effect of glycyrrhizin on the in vitro infectivity and cytopathic activity of the human immunodeficiency virus [HIV (HTLV-III/LAV)]. 

Ito, Masahiko; Nakashima, Hideki; Baba, Masanori; Pauwels, Rudi; De Clercq, Erik; Shigeta, Shiro; Yamamoto, Naoki

(Dep. Bacteriol., Fukushima Med. Coll., Fukushima 960, Japan). 

Antiviral Res., 7(3), 127-37 (English) 1987. 

Glycyrrhizin (GL), one of the plant exts., was investigated for its antiviral action on the human immunodeficiency virus [HIV (HTLV-III/LAV)] in vitro, using cytopathic effect and plaque forming assay system in MT-4 cells (a HTLV-I-carrying cell line).  Cloned Molt-4 cells (clone No. 8), which are sensitive to HIV and fuse to giant cells after infection, were also used as a parameter for cytopathic effect of HIV.  GL completely inhibited HIV-induced plaque formation in MT-4 cells at a concn. of 0.6 mM, the 50% ID being 0.15 mM.  GL completely inhibited the cytopathic effect of HIV and the HIV-specific antigen expression in MT-4 cells at a concn. of 0.3 and 0.6 mM, resp.  Furthermore, GL inhibited giant cell formation of HIV-infected Molt-4 clone No. 8 cells.  GL had no direct effect on the reverse transcriptase of HIV.  Its mechanism of anti-HIV action remains to be elucidated.

 

抗爱滋病毒

111:49739

Clinical effects of glycyrrhizin on human immunodeficiency virus disease.

Ito, Masahiko

(Fukushima Med. Coll., Fukushima, Japan). 

Jikken Igaku, 7(7), 858-60 (Japanese) 1989.

A review of the clin. effect and mechanism of action of glycyrrhizin on human immunodeficiency virus (HIV) diseases with 15 refs.

 

 

抗爱滋病毒

109:116062

Glycyrrhizin and its salts for inhibiting growth of virus of acquired immune deficiency syndrome (AIDS).

Ito, Masahiko; Nakashima, Hideki; Yamamoto, Naoki; Baba, Masanori; Shigeta, Shiro

(Minophagen Pharmaceutical Co., Japan). 

Eur. Pat. Appl. EP 255420 A2 3 Feb 1988, 12 pp.

Glycyrrhizin (I) and its pharmaceutically acceptable alkali addn. salts are useful for the treatment of AIDS.  A tablet contained I 25, potato starch 220, and Mg stearate 5 mg.  Pharmacol. expts. were carried out with human T-lymphotropic retrovirus-carrying cell line MT-4 and cloned human leukemic T-cell line Molt-4.  I at 0.5-1 mg/mL completely inhibited human immunodeficiency virus (HIV)-induced plaque formation; I showed a protective effective against the HIV-induced cytopathic effect at concns. at which I did not inhibit the growth of MT-4 cells; I did not inhibit reverse transcriptase activity of HIV, even at 10 mg/mL; the ID50 of I on the PHA and Con A responses was 2.1 and 2.0 mg/mL, resp.; I at 1 mg/mL inhibited fusion and cytopathy of HIV-infected clone No. 8 cells of Molt-4.

 

抗爱滋病毒

116:227719

Antiviral activities of glycyrrhizin and its modified compounds against human immunodeficiency virus type 1 (HIV-1) and herpes simplex virus type 1 (HSV-1) in vitro.  [Erratum to document cited in CA115(9):84866r].

Hirabayashi, Kazuhiro; Iwata, Susumu; Matsumoto, Hiroatsu; Mori, Takeo; Shibata, Shoji; Baba, Masanori; Ito, Masahiko; Shigeta, Shiro; Nakashima, Hideki; Yamamoto, Naoki

(Res. Lab., Minophagen Pharm.  Co., Kanagawa 228, Japan).  Chem. Pharm. Bull., 39(12), 3382 (English) 1991. 

Error in the text and summary have been cor.  The last expression in the abstr. should be mM instead of mM.  The errors were reflected in the abstr.

 

抗爱滋病毒

110:147191

Comparative studies of the inhibitory properties of antibiotics on human immunodeficiency virus and avian myeloblastosis virus reverse transcriptases and cellular DNA polymerases.

Take, Yukinori; Inouye, Yoshio; Nakamura, Shoshiro; Allaudeen, H. S.; Kubo, Akinori

(Sch. Med., Hiroshima Univ., Hiroshima 734, Japan). 

J. Antibiot., 42(1), 107-115 (English) 1989. 

The inhibition of human immunodeficiency virus (HIV) reverse transcriptase by certain antibiotics and related compds. was studied in comparison with that of avian myeloblastosis virus (AMV) reverse transcriptase and cellular DNA polymerases a and b.  In general, compds. that inhibited HIV reverse transcriptase also inhibited AMV reverse transcriptase.  For example, 10 mg/mL of the isoquinoline quinones used in this study inhibited approx. 80% of the activity of reverse transcriptases of HIV and AMV, but did not inhibit the activity of DNA polymerases a and b even at 50 mg/mL.  AMV enzyme was more sensitive than HIV enzyme to colistin, enduracidins A and B, janiemycin, glysperin A, and thielavins A and B.  The streptonigrin alkyl esters, however, inhibited HIV reverse transcriptase only.  Sakyomicin A, luzopeptins, ellagic acid and suramine inhibited the activities of reverse transcriptases and cellular DNA polymerases.  Structure-activity relations are discussed.

 

 

抗爱滋病毒

130:193450

Biochemical characterization of recombinant HIV-1 reverse transcriptase (rRT) as a glycyrrhizin-binding protein and the CK-II-mediated stimulation of rRT activity potently inhibited by glycyrrhetinic acid derivative.

Harada, Shigeyoshi; Maekawa, Toshiro; Haneda, Eiji; Morikawa, Yuko; Nagata, Nobuyuki; Ohtsuki, Kenzo

(Laboratory of Genetical Biochemistry, Kitasato University School of Allied Health Sciences, Sagamihara 228-8555, Japan). 

Biol. Pharm. Bull., 21(12), 1282-1285 (English) 1998

By successive Mono Q and glycyrrhizin (GL)-affinity column chromatog.  (HPLC), recombinant HIV-1 RT (rRT) was purified to apparent homogeneity from the Superdex 200 pg fraction of the crude protein ext. of E. coli BL21 transfected with pET 21a(+)/HIV-1 PR-RT.  It was found that (i) rRT functioned as an effective phosphate acceptor for recombinant human casein kinase II (rhCK-II) in vitro; (ii) this phosphorylation was inhibited by anti-HIV-1 substances [a glycyrrhetinic acid deriv. (oGA) and quercetin] and a high dose (100 mM) of GL; (iii) RNA-dependent DNA polymerase (RDDP) activity was stimulated about 2.5-fold after full phosphorylation of rRT by rhCK-II; and (i.v.) oGA as well as NCS-chromophore effectively prevented the CK-II-mediated stimulation of RDDP activity.  These results suggest that the anti-HIV-1 effect of oGA may be involved in the selective inhibition of the CK-II-mediated stimulation of HIV-1 RT at the cellular level.

 

抗爱滋病毒

130:193450

Biochemical characterization of recombinant HIV-1 reverse transcriptase (rRT) as a glycyrrhizin-binding protein and the CK-II-mediated stimulation of rRT activity potently inhibited by glycyrrhetinic acid derivative.

Harada, Shigeyoshi; Maekawa, Toshiro; Haneda, Eiji; Morikawa, Yuko; Nagata, Nobuyuki; Ohtsuki, Kenzo

(Laboratory of Genetical Biochemistry, Kitasato University School of Allied Health Sciences, Sagamihara 228-8555, Japan). 

Biol. Pharm. Bull., 21(12), 1282-1285 (English) 1998

By successive Mono Q and glycyrrhizin (GL)-affinity column chromatog.  (HPLC), recombinant HIV-1 RT (rRT) was purified to apparent homogeneity from the Superdex 200 pg fraction of the crude protein ext. of E. coli BL21 transfected with pET 21a(+)/HIV-1 PR-RT.  It was found that (i) rRT functioned as an effective phosphate acceptor for recombinant human casein kinase II (rhCK-II) in vitro; (ii) this phosphorylation was inhibited by anti-HIV-1 substances [a glycyrrhetinic acid deriv. (oGA) and quercetin] and a high dose (100 mM) of GL; (iii) RNA-dependent DNA polymerase (RDDP) activity was stimulated about 2.5-fold after full phosphorylation of rRT by rhCK-II; and (i.v.) oGA as well as NCS-chromophore effectively prevented the CK-II-mediated stimulation of RDDP activity.  These results suggest that the anti-HIV-1 effect of oGA may be involved in the selective inhibition of the CK-II-mediated stimulation of HIV-1 RT at the cellular level.

 

抗爱滋病毒

115:84866

Antiviral activities of glycyrrhizin and its modified compounds against human immunodeficiency virus type 1 (HIV-1) and herpes simplex virus type 1 (HSV-1) in vitro.

Hirabayashi, Kazuhiro; Iwata, Susumu; Matsumoto, Hiroatsu; Mori, Takeo; Shibata, Shoji; Baba,Masanori; Ito, Masahiko; Shigeta, Shiro; Nakashima, Hideki; Yamamoto, Naoki

(Res. Lab., Minophagen Pharm.  Co., Kanagawa 228, Japan). 

Chem. Pharm. Bull., 39(1), 112-15 (English) 1991.

Chem. modified compds. of glycyrrhizin (I) were synthesized and evaluated for their inhibitory effect on the replication of human immunodeficiency virus type 1 (HIV-1) and herpes simplex virus type 1 (HSV-1).  Among them, the 11-deoxy compd. having a heteroannular diene structure at the C and D rings proved as active against HIV-1 as glycyrrhizin in MT-4 and MOLT-4 cells.  It completely inhibited HIV-1-induced cytopathogenicity in both cell lines at a concn. of 0.16 mM.  The compd. was also effective against HSV-1 with a 50% inhibitory concn. of 0.5 mM.

 

抗爱滋病毒

115:41976

Synergistic virucide containing glycycoumarin, licochalcone A, and/or isolicoflavonol and glycyrrhizin for HIV virus.

Miyamoto, Kanji; Okuda, Takuo; Hirabayashi, Kazuhiro (Minophagen Pharmaceutical Co., Ltd., Japan). 

Jpn. Kokai Tokkyo Koho JP 02304024 A2 17 Dec 1990 Heisei, 6 pp. (Japan) 

The title compns. showed synergistic activities against HIV virus in cell cultures.  Each of the components also is active against HIV virus.  The components can be isolated from liquorice roots.

 

 

 

抑制爱滋病毒复制

110:185421

Mechanism of inhibitory effect of glycyrrhizin on replication of human immunodeficiency virus (HIV).

Ito, Masahiko; Sato, Akihiko; Hirabayashi, Kazuhiro; Tanabe, Fuminori; Shigeta, Shiro; Baba, Masanori; De Clercq, Erik; Nakashima, Hideki; Yamamoto, Naoki

(Dep. Bacteriol., Fukushima Med. Coll., Fukushima, Japan). 

Antiviral Res., 10(6), 289-98 (English) 1988. 

Glycyrrhizin (GL) caused a concn.-dependent inhibition of the replication of human immunodeficiency virus type 1 (HIV-1) in MOLT-4 (clone No. 8) cells at 0.075-0.6 mM.  Within this concn. range, GL also induced a concn.-dependent redn. in the protein kinase C (PKC) activity of MOLT-4 (clone No. 8) cells.  A well-known PKC inhibitor, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7), also proved inhibitory to HIV-1 replication in MOLT-4 (clone No. 8) cells.  PKC inhibition may thus be one of the mechanisms by which GL inhibits HIV-1 replication.  In addn., GL may also owe its anti-HIV-1 activity, at least in part, to an interference with virus-cell binding, since the compd. at 1.2 mM partially inhibited the adsorption of radiolabeled HIV-1 particles to MT-4 cells.  At this concn., GL also suppressed giant cell formation induced by co-culturing MOLT-4 (clone No. 8) cells with MOLT-4/HTLV-IIIB cells, whereas the PKC inhibitor H-7 failed to do so.

 

抗爱滋病毒 - 抑制HIV病毒复制

126:166125

Therapeutic effects of glycyrrhizin in mice infected with LP-BM5 murine retrovirus and mechanisms involved in the prevention of disease progression.

Watanbe, Hisami; Miyaji, Chikako; Makino, Masahiko; Abo, Toru

(Department of Immunology, Niigata University School of Medicine, Niigata 951, Japan). 

Biotherapy (Dordrecht, Neth.), 9(4), 209-220 (English) 1996

Glycyrrhizin (GL), a plant ext., has been evaluated for its inhibitory effect on HIV replication in vitro and for its improvement of clin. symptoms in HIV-infected patients.  In this study, we used GL in a murine AIDS model (MAIDS) to evaluate these effects.  C57BL/6 mice were inoculated with LP-BM5 murine leukemia virus to cause MAIDS.  Treatment with GL supplemented with glycine and cysteine (Stronger Neo-Minophagen C, SNMC) was then begun on day 0 or 4 wk after virus inoculation.  SNMC was administered three times a week for up to 19 wk.  Immunol. abnormalities were monitored with respect to the surface phenotype identified by two-color staining for CD3 and IL-2 receptor b-chain.  All mice infected with the virus alone developed MAIDS and died by 14 wk after infection.  The immunopathogenesis was estd. to be an abnormal expansion of intermediate CD3 cells (i.e., extrathymic T cells) as well as other types of lymphocytes.  SNMC did not change the total mortality rate.  However, some mice that began the treatment on day 0 or 4 wk after infection survived 3 wk longer.  Splenomegaly and lymphadenopathy in such mice were suppressed.  These mice showed normal phenotypic features and normal responses to Con A.  These results suggest that SNMC is effective in some MAIDS mice in preventing the progression of disease.  When lymphocytes isolated from the liver, spleen and lymph nodes of diseased mice were cultured in vitro, they showed a spontaneous proliferation.  Interestingly, such proliferation was inhibited by addn. of liver lymphocytes, but not splenic lymphocytes, obtained from normal or SNMC-treated mice.  Since liver lymphocytes contains intermediate CD3 cells with autoreactivity, they may possibly suppress the progression of disease.

 

抗病毒 – 杀病毒剂专利

111:58268

Glycyrrhizin derivatives as virucides.

Isowa, Yoshikazu; Sato, Yoshiaki; Nakajima, Yoshiharu; Yamamoto, Naoki

(Fujirebio, Inc., Japan). 

Jpn. Kokai Tokkyo Koho JP 63243093 A2 7 Oct 1988 Showa, 5 pp. (Japan)  CODEN: JKXXAF.  CLASS:

The title derivs. I (M = H, NH4, alkali metal) are prepd. as virucides for treatment and prophylaxis of AIDS.  A soln. of 8.2 g glycyrrhizin in pyridine was treated with ClSO3H at 0?then the mixt. was stirred overnight and treated with aq. NH3 to give 5.0 g I (M = NH4) (II).  II showed effective dosage of 0.25-2.5 mg/mL in tests against HIV in MT-4 cells, vs., 1.25 mg/mL for glycyrrhizin.