Abstract
Historical sources for the use of Glycyrrhiza species include ancient manuscripts from China, India and Greece. They all mention its use for symptoms of viral respiratory tract infections and hepatitis. Randomized controlled trials confirmed that the Glycyrrhiza glabra derived compound glycyrrhizin and its derivatives reduced hepatocellular damage in chronic hepatitis B and C. In hepatitis C virus‐induced cirrhosis the risk of hepatocellular carcinoma was reduced. Animal studies demonstrated a reduction of mortality and viral activity in herpes simplex virus encephalitis and influenza A virus pneumonia. In vitro studies revealed antiviral activity against HIV‐1, SARS related coronavirus, respiratory syncytial virus, arboviruses, vaccinia virus and vesicular stomatitis virus.
Mechanisms for antiviral activity of Glycyrrhiza spp. include reduced transport to the membrane and sialylation of hepatitis B virus surface antigen, reduction of membrane fluidity leading to inhibition of fusion of the viral membrane of HIV‐1 with the cell, induction of interferon gamma in T‐cells, inhibition of phosphorylating enzymes in vesicular stomatitis virus infection and reduction of viral latency.
Future research needs to explore the potency of compounds derived from licorice in prevention and treatment of influenza A virus pneumonia and as an adjuvant treatment in patients infected with HIV resistant to antiretroviral drugs. Copyright © 2007 John Wiley & Sons, Ltd.
Keywords: licorice, glycyrrhizin, glycyrrhetinic acid, influenza, hepatitis, SARS
REFERENCES
- Abe N, Ebina T, Ishida N. 1982. Interferon induction by glycyrrhizin and glycyrrhetinic acid in mice. Microbiol Biol 26: 535–539. [DOI] [PubMed] [Google Scholar]
- Acharya SK, Dasarathy S, Tandon A, Joshi YK, Tandon BN. 1993. A preliminary open trial on interferon stimulator (SNMC) derived from Glycyrrhiza glabra in the treatment of subacute hepatic failure. Indian J Med Res 98: 69–74. [PubMed] [Google Scholar]
- Arase Y, Ikeda K, Murashima N et al. 1997. The long term efficacy of glycyrrhizin in chronic hepatitis C patients. Cancer 79: 1494–1500. [DOI] [PubMed] [Google Scholar]
- Armanini D, Fiore C, Bielenberg J, Ragazzi E. 2005. Licorice (Glycyrrhiza glabra) In Encyclopedia of Dietary Supplements, Coates P. (ed.). Marcel Dekker Inc.: New York, 391–399. [Google Scholar]
- Armanini D, Fiore C, Matterello MJ, Bielenberg J, Palermo M. 2002. History of the endocrine effects of licorice. Exp Clin Endocrinol Diabet 110: 257–261. [DOI] [PubMed] [Google Scholar]
- Baba M, De Cleroq S, Nakashima H, Yamamoto N. 1988. Mechanism of inhibitory effect of glycyrrhizin on replication of human immunodeficiency virus (HIV). Antiviral Res 10: 289–298. [DOI] [PubMed] [Google Scholar]
- Baba M, Shigeta S. 1987. Antiviral activity of glycyrrhizin against varicella‐zoster virus in vitro . Antiviral Res 7: 99–107. [DOI] [PubMed] [Google Scholar]
- Badam L. 1997. In vitro antiviral activity of indigenous glycyrrhizin, licorice and glycyrrhizic acid (Sigma) on Japanese encephalitis virus. J Commun Dis 29: 91–99. [PubMed] [Google Scholar]
- Baltina LA. 2003. Chemical modification of glycyrrhizic acid as a route to new bioactive compounds for medicine. Curr Med Chem 10: 155–171. [DOI] [PubMed] [Google Scholar]
- Barnes J, Anderson LAA, Phillipson JD. 2002. Herbal Medicines 2nd edn. Pharmaceutical Press: London, 325–329. [Google Scholar]
- Blumenthal M, Goldberg A, Brinckmann J, Foster S. 2000. Herbal Medicine. Expanded Commission E Monographs, American Botanical Council: Austin TX, 233–239. [Google Scholar]
- Chen F, Chan KH, Jiang Y et al. 2004. In vitro susceptibility of 10 clinical isolates of SARS coronavirus to selected antiviral compounds. J Clin Virol 31: 69–75. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cinatl J, Morgenstern B, Bauer G, Chandra P, Rabenau H, Doerr HW. 2003. Glycyrrhizin, an active component of liquorice root, and replication of SARS‐associated coronavirus. Lancet 361: 2045–2046. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cohen JI. 2005. Licking latency with licorice. J Clin Invest 115: 591–593. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Crance JM, Biziagos E, Passagot J, van Cuyck‐Gandre H, Deloince R. 1990. Inhibition of hepatitis A virus replication in vitro by antiviral compounds. J Med Virol 31: 155–160. [DOI] [PubMed] [Google Scholar]
- Crance JM, Scaramozzino N, Jouan A, Garin D. 2003. Interferon, ribavirin, 6‐azauridine and glycyrrhizin: antiviral compounds active against pathogenic flaviviruses. Antiviral Res 58: 73–79. [DOI] [PubMed] [Google Scholar]
- Curreli F, Friedman‐Kein AE, Flore O. 2005. Glycyrrhizic acid alters Kaposi sarcoma‐associated herpesvirus latency, triggering p53‐mediated apoptosis in transformed B lymphocytes. J Clin Invest 115: 642–652. [DOI] [PMC free article] [PubMed] [Google Scholar]
- De Clercq E. 2000. Current lead natural products for the chemotherapy of human immunodeficiency virus (HIV) infection. Med Res Rev 20: 323–349. [DOI] [PubMed] [Google Scholar]
- Eisenburg J. 1992. Treatment of chronic hepatitis B. Part 2: Effect of glycyrrhizic acid on the course of illness. Fortschritt Med 110: 395–398. [PubMed] [Google Scholar]
- Evans WC. 2002. Trease and Evans Pharmacognosy, 15th edn. Saunders: Edinburgh‐London‐New York, 299–302. [Google Scholar]
- Fiore C, Eisenhut M, Ragazzi E, Zanchin G, Armanini D. 2005. A history of the therapeutic use of liquorice in Europe. J Ethnopharmacol 99: 317–324. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fujii T, Nakamura T, Iwamoto A. 2004. Current concepts in SARS treatment. J Infect Chemother 10: 1–7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gotoh Y, Tada K, Yamada M et al. 1987. Administration of glycyrrhizin to patients with human immunodeficiency virus infection. Igaku no Ayumi 140: 619–620. [Google Scholar]
- Harada S. 2005. The broad anti‐viral agent glycyrrhizin directly modulates the fluidity of plasma membrane and HIV‐1 envelope. Biochem J 392: 191–199. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Harada S, Maekawa T, Haneda E, Morikawa Y, Nagata N, Ohtsuki K. 1998. Biochemical characterisation of recombinant HIV‐1 reverse transcriptase (rRT) as a glycyrrhizin‐binding protein and the CK‐II‐mediated stimulation of rRT activity potently inhibited by glycyrrhetenic acid derivate. Biol Pharm Bull 21: 1282–1284. [DOI] [PubMed] [Google Scholar]
- Hoever G, Baltina L, Michaelis M et al. 2005. Antiviral activity of glycyrrhizic acid derivatives against SARS‐coronavirus. J Med Chem 48: 1256–1259. [DOI] [PubMed] [Google Scholar]
- Ikeda K, Arase Y, Kobayashi M et al. 2006. A long‐term glycyrrhizin injection therapy reduces hepatocellular carcinogenesis rate in patients with interferon‐resistant active chronic hepatitis C: A cohort study of 1249 patients. Dig Dis Sci 51: 603–609. [DOI] [PubMed] [Google Scholar]
- Isbrucker RA, Burdock GA. 2006. Risk and safety assessment on the consumption of licorice root (Gycyrrhiza sp.), its extract and powder as a food ingredient, with emphasis on the pharmacology and toxicology of glycyrrhizin. Reg Toxicol Pharmacol 46: 167–192. [DOI] [PubMed] [Google Scholar]
- Ito M, Nakashima H, Baba M et al. 1987. Inhibitory effect of glycyrrhizin on the in vitro infectivity and cytopathic activity of the human immunodeficiency virus. Antivir Res 7: 127–137. [DOI] [PubMed] [Google Scholar]
- Jeong HG, You HJ, Park SJ et al. 2002. Hepatoprotective effects of 18beta‐glycyrrhetinic acid on carbon tetrachloride‐induced liver injury: inhibition of cytochrome P450 2E1 expression. Pharmacol Res 46: 221–227. [DOI] [PubMed] [Google Scholar]
- Kiso Y, Tohkin M, Hikino H, Hattori M, Sakamoto T, Namba T. 1984. Mechanism of antihepatotoxic activity of glycyrrhizin. I: Effect on free radical generation and lipid peroxidation. Planta Med 50: 298–302. [DOI] [PubMed] [Google Scholar]
- Ko HC, Wei BL, Chiou WF. 2006. The effect of medicinal plants used in Chinese folk medicine on RANTES secretion by virus‐infected human epithelial cells. J Ethnopharmacol 107: 205–210. [DOI] [PubMed] [Google Scholar]
- Kumada H. 2002. Long‐term treatment of chronic hepatitis C with glycyrrhizin [Stronger Neo‐Minophagen C (SNMC)] for preventing liver cirrhosis and hepatocellular carcinoma. Oncology 62 (suppl 1): 94–100. [DOI] [PubMed] [Google Scholar]
- Lampi G, Deidda D, Pinza M, Pompei R. 2001. Enhancement of anti‐herpetic activity of glycyrrhizic acid by physiological proteins. Antivir Chem Chemother 12: 125–131. [DOI] [PubMed] [Google Scholar]
- Lin JC. 2003. Mechanism of action of glycyrrhizic acid in inhibition of Epstein‐Barr virus replication in vitro . Antiviral Res 59: 41–47. [DOI] [PubMed] [Google Scholar]
- Machida H, Nishitani M, Watanabe Y, Yoshimura Y, Kano F, Sakata S. 1995. Comparison of the selectivity of anti‐varicella‐zoster virus nucleoside analogues. Microbiol Biol 39: 201–206. [DOI] [PubMed] [Google Scholar]
- Miyake K, Tango T, Ota Y et al. 2002. Efficacy of Stronger Neo‐Minophagen C compared between two doses administered three times a week on patients with chronic viral hepatitis. J Gastroenterol Hepatol 17: 1198–1204. [DOI] [PubMed] [Google Scholar]
- Mori K, Sakai H, Suzuki S et al. 1989. Effects of glycyrrhizin (SNMC: stronger Neo‐Minophagen C) in hemophilia patients with HIV infection. Tohoku J Exp Med 158: 25–35. [DOI] [PubMed] [Google Scholar]
- Numazaki K, Nagata N, Sato T, Chiba S. 1994. Effect of glycyrrhizin, cyclosporin A, and tumor necrosis factor alpha on infection of U937 and MRC‐5 cells by human cytomegalovirus. J Leukoc Biol 55: 24–28. [DOI] [PubMed] [Google Scholar]
- Ohtsuki K, Iahida N. 1988. Inhibitory effect of glycyrrhizin on polypeptide phosphorylation by polypeptide‐dependent protein kinase (kinase P) in vitro . Biochem Biophys Res Commun 157: 597–604. [DOI] [PubMed] [Google Scholar]
- Orient H, Hansen BE, Willems M et al. 2006. Biochemical and histological effects of 26 weeks of glycyrrhizin treatment in chronic hepatitis C: a randomised phase II trial. J Hepatol 45: 539–546. [DOI] [PubMed] [Google Scholar]
- Pompei R, Flore O, Marccialis MA, Pani A, Loddo B. 1979. Glycyrrhizic acid inhibits virus growth and inactivates virus particles. Nature 281: 689–690. [DOI] [PubMed] [Google Scholar]
- Pompei R, Paghi L, Ingianni A, Uccheddu P. 1983. Glycyrrhizic acid inhibits influenza virus growth in embryonated eggs. Microbiologica 6: 247–250. [PubMed] [Google Scholar]
- Robbers JE, Speedie MK, Tyler VE. 1996. Pharmacognosy and Pharmacobiotechnology. Williams & Wilkins: Baltimore, 55–56. [Google Scholar]
- Sasaki H, Takei M, Kobayashi M, Pollard RB, Suzuki F. 2002. –2003. Effect of glycyrrhizin, an active component of licorice roots, on HIV replication in cultures of peripheral blood mononuclear cells from HIV‐seropositive patients. Pathobiology 70: 229–236. [DOI] [PubMed] [Google Scholar]
- Sato H, Goto W, Yamamura J et al. 1996. Therapeutic basis of glycyrrhizin on chronic hepatitis B. Antiviral Res 30: 171–177. [DOI] [PubMed] [Google Scholar]
- Sekizawa T, Yanagi K, Itoyama Y. 2001. Glycyrrhizin increases survival of mice with herpes simplex encephalitis. Acta Virol 45: 51–54. [PubMed] [Google Scholar]
- Shibata S. 2000. A drug over the millennia: pharmacognosy, chemistry, and pharmacology of licorice. Yakagaku Zasshi 120: 849–862. [DOI] [PubMed] [Google Scholar]
- Shiki Y, Shirai K, Saito Y, Yoshida S, Mori Y, Wakashin M. 1992. Effect of glycyrrhizin on lysis of hepatocyte membranes induced by anti‐liver cell membrane antibody. J Gastroenterol Hepatol 7: 12–16. [DOI] [PubMed] [Google Scholar]
- Takahara T, Watanabe A, Shiraki K. 1994. Effects of glycyrrhizin on hepatitis B surface antigen: a biochemical and morphological study. Hepatol Res 21: 601–609. [DOI] [PubMed] [Google Scholar]
- Tandon A, Tandon BN, Bhujwala RA. 2001. Treatment of subacute hepatitis with lamivudine and intravenous glycyrrhizin: a pilot study. Hepatol Res 20: 1–8. [DOI] [PubMed] [Google Scholar]
- Thyagarajan S, Jayaram S, Gopalakrishnan V, Hari R, Jeyakumar P, Sripathi M. 2002. Herbal medicines for liver diseases in India. J Gastroenterol Hepatol 17 (Suppl. 3): S370–S376. [DOI] [PubMed] [Google Scholar]
- Tochikura TS, Nakashima H, Yamamoto N. 1989. Antiviral agents with activity against human retroviruses. J Acquir Immune Defic Syndr 2: 441–447. [PubMed] [Google Scholar]
- Utsonomiya T, Kobayashi M, Pollard RB, Suzuki F. 1997. Glycyrrhizin, an active component of licorice root, reduces morbidity and mortality of mice infected with lethal doses of influenza virus. Antimicrob Agents Chemother 41: 551–556. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Van Rossum TG, Vulto AG, De Man RA, Brouwer JT, Schalm SW. 1998. Review article: glycyrrhizin as a potential treatment for chronic hepatitis C. Aliment Pharmacol Ther 12: 199–205. [DOI] [PubMed] [Google Scholar]
- Van Rossum T, Vulto A, Hop W, Schalm W. 2001. Glycyrrhizin‐induced reduction of ALT in European patients with chronic hepatitis C. Am J Gastroenterol 96: 2432–2437. [DOI] [PubMed] [Google Scholar]
- Wang JY, Guo JS, Li H, Liu SL, Zern MA. 1998. Inhibitory effect of glycyrrhizin on NF‐kappaB binding activity in CCl4‐ plus ethanol‐induced liver cirrhosis in rats. Liver 18: 180–185. [DOI] [PubMed] [Google Scholar]
- Wang XQ, Li HY, Liu XY et al. 2006. The anti‐respiratory syncytial virus effect of active compound of Glycyrrhiza GD4 in vitro . Zhang Yao Cal 29: 692–694. [PubMed] [Google Scholar]
- Zhang L, Wang B. 2002. Randomized clinical trial with two doses (100 and 40 ml) of Stronger Neo‐Minophagen C in Chinese patients with chronic hepatitis B. Hepatol Res 24: 220. [DOI] [PubMed] [Google Scholar]