Effects of glycyrrhizic acid (Viusid-Vet® powder) on the reduction of influenza virus spread and on production parameters in pigs

Main Article Content

Luis Ocampo-Camberos
Graciela Tapia
Lilia Gutiérrez
Héctor Salvador Sumano-López

Abstract

Veterinaria México OA
ISSN: 2448-6760

Cite this as:

  • Ocampo Camberos L, Tapia G, Gutiérrez L, Sumano López HS. Effects of glycyrrhizic acid (Viusid-Vet® powder) on the reduction of influenza virus spread and on production parameters in pigs. Veterinaria México OA. 2017;4(1). doi: 10.21753/vmoa.4.1.373

Influenza viruses are among the most important respiratory pathogens in pigs and humans. They cause seasonal epidemics in pigs and occasional pandemics in humans. Herbal remedies have been regarded as suitable elements to aid in controlling influenza. This study was carried out to analyse the effects of the in-feed administration of glycyrrhizic acid, the best-known component of liquorice (as Viusid-Vet® powder), in pigs suffering an outbreak of influenza. Eighty crossbred Duroc-Landrace pigs, one day post-weaning (22 days old), were included in this trial. Piglets were randomly divided into the following two groups: those treated with glycyrrhizic acid and an untreated control group. Serological measurements to assess viral load and humoral responses were carried out. Blood samples from pigs were obtained every fortnight, starting on week two and ending on week 15. With these samples, haemagglutination inhibition (HI) tests were performed, using A/swine/New Jersey/11/76 (H1N1) and A/swine/Minnesota/9088-2/98 (H3N2) as reference viruses. Quantitative RT-PCR tests against the M gene of the influenza virus were also performed to assess viral shedding from nasal swab samples on weeks 1 to 8 after the beginning of the trial. Weight variables were assessed weekly for 18 weeks. In the HI tests, treated animals showed fewer positive responses compared to the control group for H1N1 and H3N2. However, a positive response to viral protection, as assessed by HI tests, was regarded as not conclusive of humoral immune stimulation. qRT-PCR tests for viral spread exhibited a lower rate of excretion for the treated group compared to the untreated one. Hence, it appears that glycyrrhizic acid stimulates, to some extent, immune responses against pig influenza as measured by viral shedding. For mean body weight, the generalized estimating equations show a higher weight gain for pigs treated with glycyrrhizic acid than the control group (P = 0.0001). These effects may assist producers in addressing the aftermath of an influenza outbreak.

Figure 1. Results of RT-PCR viral shedding test against the M gene. (Likelihood χ21,7 = 19.2 P = 0.0001).

Keywords:
glycyrrhizic acid H1N1 H3N2 production swine-influenza virus

Article Details

References

Zhang H, Li X, Ma R, Li X, Zhou Y, Dong H, et al. Airborne spread and infection of a novel swine-origin influenza A (H1N1) virus. Virol J. 2013 Jun 22;10:204.

Morris K. Implications of narcolepsy link with swine-influenza vaccine. Lancet Infect Dis. 2013;13:396–7.

Hall JS, Teslaa JL, Nashold SW, Halpin RA, Stockwell T, Wentworth DE, et al. Evolution of a reassortant North American gull influenza virus lineage: drift, shift and stability. Virol J. 2013 Jun 6;10:179.

Olsen CW, Brown IH, Easterday BC, Van Reeth K. Swine Influenza. In: Straw BE, Zimmerman JJ, Taylor DJ, D’Allaire S, editors. Diseases of Swine. Ames, Iowa State University Press; 2006. p. 469–482.

Van Reeth K. Avian and swine influenza viruses: our current understanding of the zoonotic risk. Vet Res. 2007;38:243–260.

Francois R. Active plant extracts show promise in poultry production. Poult Int. 2006;28–31.

Frankiˇc T, Salobir J, Rezar V, Voljˇc M. Use of herbs and spices and their extracts in animal nutrition. Acta Agric Slov. 2009;94:95–102.

Baltina LA, Zarubaev VV, Orshanskaya IA, Fairushina AI, Kiselev OI, Yunusov MS. Glycyrrhicic acid derivatives as influenza A/H1N1 virus inhibitors. Bioorg Med Chem Lett. 2015;25:1742–6.

Hirabayashi K, Iwata S, Matsumoto H, Mori T, Shibata S, Baba M, et al. Antiviral activities of glycyrrhizin and its modified compounds against human immuno-deficiency virus type 1 (HIV-1) and herpes simplex virus type 1 (HSV-1) in vitro. Chem Pharm Bull (Tokyo). 1991 Jan;39(1):112–5.

Lalita B. In vitro studies on the effect of glycyrrhizin from Indian Glycyrrhiza glabra Linn on some RNA and DNA viruses. Indian J Pharmacol. 1994 Jan 7;26(3):194.

Lin JC. Mechanism of action of glycyrrhizic acid in inhibition of Epstein-Barr virus replication in vitro. Antiviral Res. 2003 Jun;59(1):41–7.

Hoever G, Baltina L, Michaelis M, Kondratenko R, Baltina L, Tolstikov GA, et al. Antiviral activity of glycyrrhizic acid derivatives against SARS-coronavirus. J Med Chem. 2005 Feb 24;48(4):1256–9.

Lee C-H, Park S-W, Kim YS, Kang SS, Kim JA, Lee SH, et al. Protective mechanism of glycyrrhizin on acute liver injury induced by carbon tetrachloride in mice. Biol Pharm Bull. 2007 Oct;30(10):1898–904.

Pompei R, Laconi S, Ingianni A. Antiviral properties of glycyrrhizic acid and its semisynthetic derivatives. Mini Rev Med Chem. 2009 Jul;9(8):996–1001.

Chavali SR, Francis T, Campbell JB. An in vitro study of immunomodulatory ef-fects of some saponins. Int J Immunopharmacol. 1987;9(6):675–83.

Ohtsuki K, Iahida N. Inhibitory effect of glycyrrhizin on polypeptide phosphor-ylation by polypeptide-dependent protein kinase (kinase P) in vitro. Biochem Biophys Res Commun. 1988 Dec 15;157(2):597–604.

Lo HH, Yen YS, Hsieh SE, Chung JG. Glycyrrhizic acid inhibits arylamine N-acet-yltransferase activity in Klebsiella pneumoniae in vitro. J Appl Toxicol JAT. 1997 Dec;17(6):385–90.

Tanaka Y, Kikuzaki H, Fukuda S, Nakatani N. Antibacterial compounds of licorice against upper airway respiratory tract pathogens. J Nutr Sci Vitaminol (Tokyo). 2001 Jun;47(3):270–3.

Krausse R, Bielenberg J, Blaschek W, Ullmann U. In vitro anti-Helicobacter py-lori activity of Extractum liquiritiae, glycyrrhizin and its metabolites. J Antimicrob Chemother. 2004 Jul;54(1):243–6.

Ocampo CL, Gómez-Verduzco G, Tapia-Perez G, Gutierrez OL, Sumano LH. Ef-fects of glycyrrhizic acid on productive and immunological variables in broilers. Braz J Poult Sci. 2016;18(In press).

Castanon JIR. History of the use of antibiotic as growth promoters in European poultry feeds. Poult Sci. 2007 Nov;86(11):2466–71.

Ocampo L, Chavez B, Tapia G, Ibarra C, Sumano H. Efficacy of a pharmaceu-tical preparation based on glycyrrhizic acid in a challenge study of white spot syndrome in white shrimp (Litopenaeus vannamei). Aquaculture. 2014 May 20;428–429:280–3.

Buchner A, Erdfelder E, Faul F. How to Use G*Power 1997 [Internet]. 2008 [cited 2016 Feb 28]. Available from: at http://www.psycho.uni.duesseldorf.do/aap/projects/gppwer/how_to_use_gpower.html

OIE 2017. Manual of Diagnostic Tests and Vaccines for Terrestrial Animals 2016 [Internet]. OIE-World Organization for Animal Health. [cited 2017 Mar 3]. Available from: http://www.oie.int/en/international-standard-setting/terrestrial-manual/access-online/

"McCulloch CE, Searle SR. One-Way Classifications. In: Generalized, Linear, and Mixed Models [Internet]. John Wiley & Sons, Inc.; 2000 [cited 2017 Mar 3]. p. 28–

Available from: http://onlinelibrary.wiley.com/doi/10.1002/0471722073. ch2/summary"

Nowakowska Z. A review of anti-infective and anti-inflammatory chalcones. Eur J Med Chem. 2007 Feb;42(2):125–37.

Racková L, Jancinová V, Petríková M, Drábiková K, Nosál R, Stefek M, et al. Mech-anism of anti-inflammatory action of liquorice extract and glycyrrhizin. Nat Prod Res. 2007 Dec;21(14):1234–41.

Utsunomiya T, Kobayashi M, Pollard RB, Suzuki F. Glycyrrhizin, an active component of licorice roots, reduces morbidity and mortality of mice infect-ed with lethal doses of influenza virus. Antimicrob Agents Chemother. 1997 Mar;41(3):551–6.

Vega DG, Morales IC, López MAV, González AM. Perfil inmunológico de los cerdos durante las primeras diez semanas de edad. Vet México. 1993;24(3):217–21.

Loving CL, Lager KM, Vincent AL, Brockmeier SL, Gauger PC, Anderson TK, et al. Efficacy in pigs of inactivated and live attenuated influenza virus vaccines against infection and transmission of an emerging H3N2 similar to the 2011-2012 H3N2v. J Virol. 2013 Sep;87(17):9895–903.

Brenes A, Roura E. Essential oils in poultry nutrition: Main effects and modes of action. Anim Feed Sci Technol. 2010 Jun 2;158(1–2):1–14.

Vaya J, Belinky PA, Aviram M. Antioxidant constituents from licorice roots: isola-tion, structure elucidation and antioxidative capacity toward LDL oxidation. Free Radic Biol Med. 1997;23(2):302–13.

Kao T-C, Shyu M-H, Yen G-C. Glycyrrhizic acid and 18beta-glycyrrhetinic acid in-hibit inflammation via PI3K/Akt/GSK3beta signaling and glucocorticoid receptor activation. J Agric Food Chem. 2010 Aug 11;58(15):8623–9.

Armanini D, Karbowiak I, Funder JW. Affinity of liquorice derivatives for min-eralocorticoid and glucocorticoid receptors. Clin Endocrinol (Oxf). 1983 Nov;19(5):609–12.

Okimasu E, Moromizato Y, Watanabe S, Sasaki J, Shiraishi N, Morimoto YM, et al. Inhibition of phospholipase A2 and platelet aggregation by glycyrrhizin, an antiinflammation drug. Acta Med Okayama. 1983 Oct;37(5):385–91.

Ohuchi K, Kamada Y, Levine L, Tsurufuji S. Glycyrrhizin inhibits prostaglandin E2 production by activated peritoneal macrophages from rats. Prostaglandins Med. 1981 Nov;7(5):457–63.

Brown IH. The epidemiology and evolution of influenza viruses in pigs. Vet Mi-crobiol. 2000 May 22;74(1–2):29–46.

Thacker E, Janke B. Swine influenza virus: zoonotic potential and vaccination strategies for the control of avian and swine influenzas. J Infect Dis. 2008 Feb 15;197 Suppl 1:S19-24.

Van Reeth K, Labarque G, De Clercq S, Pensaert M. Efficacy of vaccination of pigs with different H1N1 swine influenza viruses using a recent challenge strain and different parameters of protection. Vaccine. 2001 Aug 14;19(31):4479–86.

Vincent AL, Ma W, Lager KM, Janke BH, Richt JA. Swine influenza viruses a North American perspective. Adv Virus Res. 2008;72:127–54.

Størmer FC, Reistad R, Alexander J. Glycyrrhizic acid in liquorice–evaluation of health hazard. Food Chem Toxicol Int J Publ Br Ind Biol Res Assoc. 1993 Apr;31(4):303–12.