Virology Journal | |
Anti-rotaviral effects of Glycyrrhiza uralensis extract in piglets with rotavirus diarrhea | |
Kyoung-Oh Cho2  Woo Song Lee3  Sang-Ik Park2  Su-Jin Park3  Young Bae Ryu3  Hyung-Jun Kwon3  Ju-Hwan Lee4  Kyu-Yeol Son2  Myra Hosmillo2  Deok-Song Kim2  Young-Ju Jeong1  Ji-Yun Kim2  Eun-Hye Ryu2  Jun-Gyu Park2  Hyun-Jeong Kim2  Mia Madel Alfajaro2  | |
[1] Present address: Department of Clinical Pathology, College of Medicine, Seonam University, Namwon, 590-711, Republic of Korea;Biotherapy Human Resources Center, College of Veterinary Medicine, Chonnam National University, Gwangju, 500-757, Republic of Korea;Eco- Friendly Biomaterial Research Center and AI Control Material Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongup, 580- 185, Republic of Korea;Chonnam National University Veterinary Teaching Hospital, Gwangju, 500-757, Republic of Korea | |
关键词: Anti-rotaviral drug; Glycyrrhiza uralensis extract; Enteritis; Rotavirus; | |
Others : 1152725 DOI : 10.1186/1743-422X-9-310 |
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received in 2012-07-03, accepted in 2012-12-10, 发布年份 2012 | |
【 摘 要 】
Background
Since rotavirus is one of the leading pathogens that cause severe gastroenteritis and represents a serious threat to human and animal health, researchers have been searching for cheap, safe, and effective anti-rotaviral drugs. There is a widespread of interest in using natural products as antiviral agents, and among them, licorice derived from Glycyrrhiza spp. has exerted antiviral properties against several viruses. In this study, anti-rotaviral efficacy of Glycyrrhiza uralensis extract (GUE) as an effective and cheaper remedy without side-effects was evaluated in colostrums-deprived piglets after induction of rotavirus diarrhea.
Methods
Colostrums-deprived piglets were inoculated with porcine rotavirus K85 (G5P[7]) strain. On the onset of diarrhea, piglets were treated with different concentration of GUE. To evaluate the antiviral efficacy of GUE, fecal consistency score, fecal virus shedding and histological changes of the small intestine, mRNA expression levels of inflammation-related cytokines (IL8, IL10, IFN-β, IFN-γ and TNF-α), signaling molecules (p38 and JNK), and transcription factor (NFκB) in the small intestine and spleen were determined.
Results
Among the dosages (100-400 mg/ml) administrated to animals, 400 mg/ml of GUE cured diarrhea, and markedly improved small intestinal lesion score and fecal virus shedding. mRNA expression levels of inflammation-related cytokines (IL8, IL10, IFN-β, IFN-γ and TNF-α), signaling molecules (p38 and JNK), and transcription factor (NFκB) in the small intestine and spleen were markedly increased in animals with RVA-induced diarrhea, but dose- dependently decreased in GUE treated animals after RVA-induced diarrhea.
Conclusions
GUE cures rotaviral enteritis by coordinating antiviral and anti-inflammatory effects. Therapy of this herbal medicine can be a viable medication for curing rotaviral enteritis in animals and humans.
【 授权许可】
2012 Alfajaro et al.; licensee BioMed Central Ltd.
【 预 览 】
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Figure 1. | 44KB | Image | download |
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【 参考文献 】
- [1]Boshuizen JA, Reimerink JHJ, Male AM, van Ham VJJ, Koopmans MPG, Buller HA, Dekker J, Einerhand AW: Changes in small intestinal homeostasis, morphology, and gene expression during rotavirus infection of infant mice. J Virol 2003, 77:13005-13016.
- [2]Tate JE, Burton AH, Boschi-Pinto C, Steele AD, Duque J, Parashar UD, WHO-coordinated Global Rotavirus Surveillance Network: 2008 estimate of worldwide rotavirus-associated mortality in children younger than 5 years before the introduction of universal rotavirus vaccination programs: a systematic review and meta-analysis. Lancet Infect Dis 2012, 12:136-141.
- [3]Pesavento JB, Crawford SE, Estes MK: Rotavirus Proteins: Structure and Assembly. Curr Top Microbiol Immunol 2006, 309:189-219.
- [4]Anderson EJ: Rotavirus vaccines: viral shedding and risk of transmission. Lancet Infect Dis 2008, 8:642-649.
- [5]Baek SH, Lee JG, Park SY, Bae ON, Kim DH, Park JH: Pectic polysaccharides from Panax ginseng as the antirotavirus principals in ginseng. Biomacromolecules 2010, 11:2044-2052.
- [6]Lian ZH, Yang DH: Clinical studies on treatment of infantile rotavirus diarrhea with famotidine in 54 cases. J Clin Intern Med 1996, 13:28. in Chinese
- [7]Smee DF, Sidwell RW, Clark SM, Barnett BB, Spendlove RS: Inhibition of rotaviruses by selected antiviral substances: mechanisms of viral inhibition and in vivo activity. Antimicrob Agents Chemother 1982, 21:66-73.
- [8]Zhong Y: Clinical studies on treatment of infantile rotavirus diarrhea with cimetidine in 186 cases. J Nantong Med Coll 1996, 16:269. in Chinese
- [9]Gu Y, Gu Q, Kodama H, Mueller WE, Ushijima H: Development of antirotavirus agents in Asia. Pediatr Int 2000, 42:440-447.
- [10]Mukoyama A, Ushijima H, Unten S, Nishimura S, Yoshihara M, Sakagami H: Effect of pine seed shell extract on rotavirus and enterovirus infections. Lett Appl Microbiol 1991, 103:109-111.
- [11]Takahashi K, Matsuda M, Ohashi K, Taniguchi K, Nakagomi O, Abe Y, Mori S, Sato N, Okutani K, Shigeta S: Analysis of anti-rotavirus activity of extract from Stevia rebaudiana. Antiviral Res 2001, 49:15-24.
- [12]Yolken RH, Peterson JA, Vonderfecht SL, Foust ET, Midthun K, Newburg DS: Human milk mucin inhibits rotavirus replication and prevents experimental gastroenteritis. J Clin Invest 1992, 90:1984-1991.
- [13]Newburg DS, Peterson JA, Ruiz-Palacios GM, Matson DO, Morrow AL, Shults J, Guerrero ML, Chaturvedi P, Newburg SO, Scallan CD, Taylor MR, Ceriani RL, Pickering LK: Role of human-milk lactadherin in protection against symptomatic rotavirus infection. Lancet 1998, 351:1160-1164.
- [14]Andres A, Donovan SM, Kuhlenschmidt TB, Kuhlenschmidt MS: Isoflavones at concentrations present in soy infant formula inhibit rotavirus infection in vitro. J Nutr 2007, 137:2068-2073.
- [15]Asl MN, Hosseinzadeh H: Review of pharmacological effects of Glycyrrhiza sp. and its bioactive compounds. Phytother Res 2008, 22:709-724.
- [16]Fiore C, Eisenhunt M, Krausse R, Ragazzi E, Pellati D, Armanini D, Bielenberg J: Antiviral effects of Glycyrrhiza species. Phytother Res 2008, 22:141-148.
- [17]Dong S, Inoue A, Zhu Y, Tanji M, Kiyama R: Activation of rapid signaling pathways and subsequent transcriptional regulation for the proliferation of breast cancer MCF-7 cells by the treatment with an extract of Glycyrrhiza glabra root. Food Chem Toxicol 2007, 45:270-278.
- [18]Cinatl J, Morgenstern B, Bauer G, Chandra P, Rabenau H, Doerr HW: Glycyrrhizin, an active component of liquorice roots, and replication of SARS-associated coronavirus. Lancet 2003, 361:2045-2046.
- [19]Geiler J, Michaelis M, Naczk P, Leutz A, Langer K, Doerr HW, Cinatl J Jr: N-acetyl-L-cysteine (NAC) inhibits virus replication and expression of pro-inflammatory molecules in A549 cells infected with highly pathogenic H5N1 influenza A virus. Biochem Pharmacol 2010, 79:413-430.
- [20]Kwon HJ, Kim HH, Ryu YB, Kim JH, Jeong HJ, Lee SW, Chang JS, Cho KO, Rho MC, Park SJ, Lee WS: In vitro anti-rotavirus activity of polyphenol compounds isolated from the roots of Glycyrrhiza uralensis. Bioorg Med Chem 2010, 18:7668-7674.
- [21]Hardy ME, Hendricks JM, Paulson JM, Faunce NR: 18β-glycyrrhetinic acid inhibits rotavirus replication in culture. Virol J 2012, 9:96. BioMed Central Full Text
- [22]Vega CG, Bok M, Vlasova AN, Chattha KS, Fernandez FM, Wigdorovitz A, Parreno VG, Saif LJ: IgY antibodies protects against human rotavirus induced diarrhea in the neonatal gnotobiotic piglet disease model. PLoS One 2012, 7:e42788.
- [23]Matthijnssens J, Ciarlet M, Heiman E, Arijs I, Delbeke T, McDonald SM, Palombo EA, Iturriza-Gomara M, Maes P, Patton JT, Rahman M, Van Ranst M: Full genome based classification of rotaviruses reveals a common origin between human Wa-like and porcine rotavirus strains and human DS-1-like and bovine rotavirus strains. J Virol 2008, 82:3204-3219.
- [24]Kim HJ, Park JG, Matthijnssens J, Lee JH, Bae YC, Alfajaro MM, Park SI, Kang MI, Cho KO: Intestinal and extra-intestinal pathogenicity of a bovine reassortant rotavirus in calves and piglets. Vet Microbiol 2011, 152:291-303.
- [25]Casola A, Garofalo RP, Crawford SE, Estes MK, Mercurio F, Crowe SE, Brasier AR: Interleukin-8 gene regulation in intestinal epithelial cells infected with rotavirus: role of viral-induced IkB kinase activation. Virol 2002, 298:8-19.
- [26]La Monica R, Kocer SS, Nazarova J, Dowling W, Geimonen E, Shaw RD, Mackow ER: VP4 differentially regulates TRAF2 signaling, disengaging JNK activation while directing NFκB to effect rotavirus-specific cellular responses. J Biol Chem 2001, 276:19889-19896.
- [27]Michaelis M, Geiler J, Naczk P, Sithisarn P, Leutz A, Doerr HW, Cinatl J Jr: Glycyrrhizin exerts antioxidative effects in H5N1 influenza A virus-infected cells and inhibits virus replication and pro-inflammatory gene expression. PLoS One 2011, 6:1-9.
- [28]Zachos G, Clements B, Conner J: Herpes simplex virus type 1 infection stimulates p38/c-Jun N-terminal mitogen-activated protein kinase pathways and activates transcription factor AP-1. J Biol Chem 1999, 1999(274):5097-5103.
- [29]Graff JW, Ettayebi K, Hardy ME: Rotavirus NSP1 inhibits NFkappaB activation by inducing proteasome-dependent degradation of beta-TrCP: a novel mechanism of IFN antagonism. PLoS Pathog 2009, 5:e1000280.
- [30]Kim JK, Oh SM, Kwon HS, Oh YS, Lim SS, Shin HK: Anti-inflammatory effect of roasted licorice extracts on lipopolysaccharide responses in murine macrophage. Biochem Biophys Res Commun 2006, 345:1215-1223.
- [31]Wang CY, Kao TC, Lo WH, Yen GC: Glycyrrhizic acid and 18β-glycyrrhetinic acid modulate lipopolysaccharide-induced inflammatory response by suppression of NFκB through PK3K p110δ and p110γ inhibition. J Agric Food Chem 2011, 2011(59):7726-7733.
- [32]Chang YL, Chen CL, Kuo CL, Chen BC, You JS: Glycyrrhetinic acid inhibits ICAM-1 expression via blocking JNK and NF-kappaB pathways in TNF-alpha-activated endothelial cells. Acta Pharmacol Sin 2010, 31:546-533.
- [33]McCubrey JA, Lahair MM, Franklin RA: Reactive oxygen species-induced activation of the MAP kinase signaling pathways. Antioxid Redox Signal 2006, 8:1775-1789.
- [34]Chiang E, Dang O, Anderson K, Matsuzawa A, Ichijo H, David M: Cutting edge: apoptosis-regulating signal kinase 1 is required for reactive oxygen species-mediated activation of IFN regulatory factor 3 by lipopolysaccharide. J Immunol 2006, 176:5720-5724.
- [35]Kim HJ, Park SI, Ha TPM, Jeong YJ, Kim HH, Kwon HJ, Kang MI, Cho KO, Park SJ: Detection and genotyping of Korean porcine rotaviruses. Vet Microbiol 2010, 144:274-286.
- [36]Gonzalez AM, Azevedo MS, Jung K, Vlasova A, Zhang W, Saif LJ: Innate immune responses to human rotavirus in the neonatal gnotobiotic piglet diseases model. Immunol 2010, 131:242-256.
- [37]Ward LA, Rosen BI, Yuan L, Saif LJ: Pathogenesis of an attenuated and virulent strain of group A human rotavirus in neonatal gnotobiotic pigs. J Gen Virol 1996, 77:1431-1441.
- [38]Cho JY, Baik KU, Jung JH, Park MH: In vitro anti-inflammatory effects of cynaropicirin, a sesquiterpene lactone from Saussurea lappa. Eur J Pharmacol 2000, 398:399-407.
- [39]Collado-Romero M, Arce C, Ramirez-Boo M, Carvajal A, Garrido JJ: Quantitative analysis of the immune response upon Salmonella typhimurium infection along the porcine intestinal gut. Vet Res 2010, 41:23-34.