Abstract
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% lethal doses of the virus were treated intraperitoneally with 10 mg of GR per kg of body weight 1 day before infection and 1 and 4 days postinfection, all of the mice survived over the 21-day experimental 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 addition, 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-gamma) monoclonal antibody. These results suggest that GR may protect mice exposed to a lethal amount of influenza virus through the stimulation of IFN-gamma production by T cells, because T cells have been shown to be producer cells of IFN-gamma stimulated with the compound.
Full Text
The Full Text of this article is available as a PDF (91.0 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Abe N., Ebina T., Ishida N. Interferon induction by glycyrrhizin and glycyrrhetinic acid in mice. Microbiol Immunol. 1982;26(6):535–539. doi: 10.1111/j.1348-0421.1982.tb00207.x. [DOI] [PubMed] [Google Scholar]
- Baumgarth N., Brown L., Jackson D., Kelso A. Novel features of the respiratory tract T-cell response to influenza virus infection: lung T cells increase expression of gamma interferon mRNA in vivo and maintain high levels of mRNA expression for interleukin-5 (IL-5) and IL-10. J Virol. 1994 Nov;68(11):7575–7581. doi: 10.1128/jvi.68.11.7575-7581.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- DAVIES W. L., GRUNERT R. R., HAFF R. F., MCGAHEN J. W., NEUMAYER E. M., PAULSHOCK M., WATTS J. C., WOOD T. R., HERMANN E. C., HOFFMANN C. E. ANTIVIRAL ACTIVITY OF 1-ADAMANTANAMINE (AMANTADINE). Science. 1964 May 15;144(3620):862–863. doi: 10.1126/science.144.3620.862. [DOI] [PubMed] [Google Scholar]
- Dolin R. Antiviral chemotherapy and chemoprophylaxis. Science. 1985 Mar 15;227(4692):1296–1303. doi: 10.1126/science.2983421. [DOI] [PubMed] [Google Scholar]
- FINNEY R. S., SOMERS G. F. The antiinflammatory activity of glycyrrhetinic acid and derivatives. J Pharm Pharmacol. 1958 Oct;10(10):613–620. doi: 10.1111/j.2042-7158.1958.tb10349.x. [DOI] [PubMed] [Google Scholar]
- Hattori T., Ikematsu S., Koito A., Matsushita S., Maeda Y., Hada M., Fujimaki M., Takatsuki K. Preliminary evidence for inhibitory effect of glycyrrhizin on HIV replication in patients with AIDS. Antiviral Res. 1989 Jun-Jul;11(5-6):255–261. doi: 10.1016/0166-3542(89)90035-1. [DOI] [PubMed] [Google Scholar]
- Hoshino A., Takenaka H., Mizukoshi O., Imanishi J., Kishida T., Tovey M. G. Effect of anti-interferon serum of influenza virus infection in mice. Antiviral Res. 1983 Mar;3(1):59–65. doi: 10.1016/0166-3542(83)90015-3. [DOI] [PubMed] [Google Scholar]
- ISHIDA N., KOSAKA Y., SASAKI Y. Studies on experimental influenza in mice. II. Absolute amount of virus introduced into the respiratory tract of mice by standard inhalation procedure. Tohoku J Exp Med. 1959 Dec 25;71:151–161. [PubMed] [Google Scholar]
- Kent J. H., Chapman L. E., Schmeltz L. M., Regnery H. L., Cox N. J., Schonberger L. B. Influenza surveillance--United States, 1991-92. MMWR CDC Surveill Summ. 1992 Sep 4;41(5):35–43. [PubMed] [Google Scholar]
- Knight V., Gilbert B. E. Ribavirin aerosol treatment of influenza. Infect Dis Clin North Am. 1987 Jun;1(2):441–457. [PubMed] [Google Scholar]
- Numazaki K., Nagata N., Sato T., Chiba S. Effect of glycyrrhizin, cyclosporin A, and tumor necrosis factor alpha on infection of U-937 and MRC-5 cells by human cytomegalovirus. J Leukoc Biol. 1994 Jan;55(1):24–28. doi: 10.1002/jlb.55.1.24. [DOI] [PubMed] [Google Scholar]
- Perrotta D. M., Decker M., Glezen W. P. Acute respiratory disease hospitalizations as a measure of impact of epidemic influenza. Am J Epidemiol. 1985 Sep;122(3):468–476. doi: 10.1093/oxfordjournals.aje.a114128. [DOI] [PubMed] [Google Scholar]
- Pompei R., Flore O., Marccialis M. A., Pani A., Loddo B. Glycyrrhizic acid inhibits virus growth and inactivates virus particles. Nature. 1979 Oct 25;281(5733):689–690. doi: 10.1038/281689a0. [DOI] [PubMed] [Google Scholar]
- Saito N., Suzuki F., Ishida N. Antiviral effect of interferon on influenza virus infection in mice. Tohoku J Exp Med. 1983 Apr;139(4):355–363. doi: 10.1620/tjem.139.355. [DOI] [PubMed] [Google Scholar]
- Saito N., Suzuki F., Sasaki K., Ishida N. Antiviral and interferon-inducing activity of a new glutarimide antibiotic, 9-methylstreptimidone. Antimicrob Agents Chemother. 1976 Jul;10(1):14–19. doi: 10.1128/aac.10.1.14. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sakamoto M., Suzuki F., Arai S., Takishima T., Ishida N. Experimental myocarditis induced in mice by infection with influenza A2 virus. Microbiol Immunol. 1981;25(2):173–181. doi: 10.1111/j.1348-0421.1981.tb00020.x. [DOI] [PubMed] [Google Scholar]
- Sarawar S. R., Doherty P. C. Concurrent production of interleukin-2, interleukin-10, and gamma interferon in the regional lymph nodes of mice with influenza pneumonia. J Virol. 1994 May;68(5):3112–3119. doi: 10.1128/jvi.68.5.3112-3119.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shimomura E., Suzuki F., Ishida N. Characterization of cells infiltrating the lungs of x-irradiated and nude mice after influenza virus infection. Microbiol Immunol. 1982;26(2):129–138. doi: 10.1111/j.1348-0421.1982.tb00162.x. [DOI] [PubMed] [Google Scholar]
- Shinada M., Azuma M., Kawai H., Sazaki K., Yoshida I., Yoshida T., Suzutani T., Sakuma T. Enhancement of interferon-gamma production in glycyrrhizin-treated human peripheral lymphocytes in response to concanavalin A and to surface antigen of hepatitis B virus. Proc Soc Exp Biol Med. 1986 Feb;181(2):205–210. doi: 10.3181/00379727-181-42241. [DOI] [PubMed] [Google Scholar]
- Suzuki F., Ishida N., Suzuki M., Sato T., Suzuki S. Effect of the interferon inducer, dextran phosphate, on influenza virus infection in mice. Proc Soc Exp Biol Med. 1975 Sep;149(4):1069–1075. doi: 10.3181/00379727-149-38960. [DOI] [PubMed] [Google Scholar]
- Suzuki F., Oya J., Ishida N. Effect of antilymphocyte serum on influenza virus infection in mice. Proc Soc Exp Biol Med. 1974 May;146(1):78–84. doi: 10.3181/00379727-146-38047. [DOI] [PubMed] [Google Scholar]
- Suzuki F., Pollard R. B. Mechanism for the suppression of gamma-interferon responsiveness in mice after thermal injury. J Immunol. 1982 Nov;129(5):1811–1815. [PubMed] [Google Scholar]
- Suzuki F., Saito N., Ishida N. [Antiviral effects of interferons and their inducers in experimental animals (author's transl)]. Tanpakushitsu Kakusan Koso. 1976 Apr;21(4):260–270. [PubMed] [Google Scholar]
- Suzuki F., Suzuki C., Shimomura E., Maeda H., Fujii T., Ishida N. Antiviral and interferon-inducing activities of a new peptidomannan, KS-2, extracted from culture mycelia of Lentinus edodes. J Antibiot (Tokyo) 1979 Dec;32(12):1336–1345. doi: 10.7164/antibiotics.32.1336. [DOI] [PubMed] [Google Scholar]
- Tobita K., Sugiura A., Enomote C., Furuyama M. Plaque assay and primary isolation of influenza A viruses in an established line of canine kidney cells (MDCK) in the presence of trypsin. Med Microbiol Immunol. 1975 Dec 30;162(1):9–14. doi: 10.1007/BF02123572. [DOI] [PubMed] [Google Scholar]
- Utsunomiya T., Kobayashi M., Herndon D. N., Pollard R. B., Suzuki F. Glycyrrhizin (20 beta-carboxy-11-oxo-30-norolean-12-en-3 beta-yl-2-O-beta-D-glucopyranuronosyl-alpha-D-glucopyranosiduronic acid) improves the resistance of thermally injured mice to opportunistic infection of herpes simplex virus type 1. Immunol Lett. 1995 Jan;44(1):59–66. doi: 10.1016/0165-2478(94)00183-r. [DOI] [PubMed] [Google Scholar]