Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Fructus Amomi Cardamomi Extract Inhibits Coxsackievirus-B3 Induced Myocarditis in a Murine Myocarditis Model

  • Lee, Yun-Gyeong (Department of Biomedical Science, Jungwon University) ;
  • Park, Jung-Ho (Bio-Evaluation Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Jeon, Eun-Seok (Cardiac and Vascular Center, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Kim, Jin-Hee (College of Herbal Bio-Industry, Daegu Haany University) ;
  • Lim, Byung-Kwan (Department of Biomedical Science, Jungwon University)
  • Received : 2016.05.18
  • Accepted : 2016.08.17
  • Published : 2016.11.28
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Abstract

Coxsackievirus B3 (CVB3) is the main cause of acute myocarditis and dilated cardiomyopathy. Plant extracts are considered as useful materials to develop new antiviral drugs. We had previously selected candidate plant extracts, which showed anti-inflammatory effects. We examined the antiviral effects by using a HeLa cell survival assay. Among these extracts, we chose the Amomi Cardamomi (Amomi) extract, which showed strong antiviral effect and preserved cell survival in CVB3 infection. We investigated the mechanisms underlying the ability of Amomi extract to inhibit CVB3 infection and replication. HeLa cells were infected by CVB3 with or without Amomi extract. Erk and Akt activities, and their correlation with virus replication were observed. Live virus titers in cell supernatants and viral positive- and negative-strand RNA amplification were measured. Amomi extract significantly increased HeLa cell survival in different concentrations ($100-10{\mu}g/ml$). CVB3 capsid protein VP1 expression (76%) and viral protease 2A-induced eIF4G1 cleavage (70%) were significantly decreased in Amomi extract ($100{\mu}g/ml$) treated cells. The levels of positive- (20%) and negative-strand (80%) RNA were dramatically decreased compared with the control, as revealed by reverse transcription-PCR. In addition, Amomi extract improved mice survival (51% vs 26%) and dramatically reduced heart inflammation in a CVB3-induced myocarditis mouse model. These results suggested that Amomi extract significantly inhibited Enterovirus replication and myocarditis damage. Amomi may be developed as a therapeutic drug for Enterovirus.

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References

  1. Badorff C, Berkely N, Mehrotra S, Talhouk JW, Rhoads RE, Knowlton KU. 2000. Enteroviral protease 2A directly cleaves dystrophin and is inhibited by a dystrophin-based substrate analogue. J. Biol. Chem. 275: 11191-11197. https://doi.org/10.1074/jbc.275.15.11191
  2. Chen TC, Weng KF, Chang SC, Lin JY, Huang PN, Shih SR. 2008. Development of antiviral agents for enteroviruses. J. Antimicrob. Chemother. 62: 1169-1173. https://doi.org/10.1093/jac/dkn424
  3. Choi HG, Je IG, Kim GJ, Choi H, Kim SH, Kim JA, Lee KS. 2015. Anti-allergic inflammatory activities of compounds of amomi fructus. Nat. Prod. Commun. 10: 631-632.
  4. Esfandiarei M, Luo H, Yanagawa B, Suarez A, Dabiri D, Zhang J, McManus BM. 2004. Protein kinase B/Akt regulates coxsackievirus B3 replication through a mechanism which is not caspase dependent. J. Virol. 78: 4289-4298. https://doi.org/10.1128/JVI.78.8.4289-4298.2004
  5. Feldman AM, McNamara D. 2000. Myocarditis. N. Engl. J. Med. 343: 1388-1398. https://doi.org/10.1056/NEJM200011093431908
  6. Herskowitz A, Beisel KW, Wolfgram LJ, Rose NR. 1985. Coxsackievirus B3 murine myocarditis: wide pathologic spectrum in genetically defined inbred strains. Hum. Pathol. 16: 671-673. https://doi.org/10.1016/S0046-8177(85)80149-0
  7. Kearney MT, Cotton JM, Richardson PJ, Shah AM. 2001. Viral myocarditis and dilated cardiomyopathy: mechanisms, manifestations, and management. Postgrad. Med. J. 77: 4-10. https://doi.org/10.1136/pmj.77.903.4
  8. Kim JM, Lim BK, Ho SH, Yun SH, Shin JO, Park EM, et al. 2006. TNFR-Fc fusion protein expressed by in vivo electroporation improves survival rates and myocardial injury in coxsackievirus induced murine myocarditis. Biochem. Biophys. Res. Commun. 344: 765-771. https://doi.org/10.1016/j.bbrc.2006.03.170
  9. Knowlton KU, Badorff C. 1999. The immune system in viral myocarditis: maintaining the balance. Circ. Res. 85: 559-561. https://doi.org/10.1161/01.RES.85.6.559
  10. Knowlton KU, Jeon ES, Berkley N, Wessely R, Huber S. 1996. A mutation in the puff region of VP2 attenuates the myocarditic phenotype of an infectious cDNA of the Woodruff variant of coxsackievirus B3. J. Virol. 70: 7811-7818.
  11. Kumar S, Pandey AK. 2013. Chemistry and biological activities of flavonoids: an overview. Scientific World Journal 2013: 162750.
  12. Lim BK, Choe SC, Shin JO, Ho SH, Kim JM, Yu SS, et al. 2002. Local expression of interleukin-1 receptor antagonist by plasmid DNA improves mortality and decreases myocardial inflammation in experimental coxsackieviral myocarditis. Circulation 105: 1278-1281.
  13. Lim BK, Choi JH, Nam JH, Gil CO, Shin JO, Yun SH, et al. 2006. Virus receptor trap neutralizes coxsackievirus in experimental murine viral myocarditis. Cardiovasc. Res. 71: 517-526. https://doi.org/10.1016/j.cardiores.2006.05.016
  14. Lim BK, Kim JH. 2014. ORI2 inhibits coxsackievirus replication and myocardial inflammation in experimental murine myocarditis. Biol. Pharm. Bull. 37: 1650-1654. https://doi.org/10.1248/bpb.b14-00408
  15. Lim BK, Nam JH, Gil CO, Yun SH, Choi JH, Kim DK, Jeon ES. 2005. Coxsackievirus B3 replication is related to activation of the late extracellular signal-regulated kinase (ERK) signal. Virus Res. 113: 153-157. https://doi.org/10.1016/j.virusres.2005.04.018
  16. Lim BK, Xiong D, Dorner A, Youn TJ, Yung A, Liu TI, et al. 2008. Coxsackievirus and adenovirus receptor (CAR) mediates atrioventricular-node function and connexin 45 localization in the murine heart. J. Clin. Invest. 118: 2758-2770. https://doi.org/10.1172/JCI34777
  17. Lim BK, Yun SH, Gil CO, Ju ES, Choi JO, Kim DK, Jeon ES. 2012. Foreign gene transfer to cardiomyocyte using a replication-defective recombinant coxsackievirus B3 without cytotoxicity. Intervirology 55: 201-209. https://doi.org/10.1159/000324541
  18. Lim BK, Yun SH, Ju ES, Gil CO, Kim DK, Jeon ES. 2012. Role of the myristoylation site in expressing exogenous functional proteins in coxsackieviral vector. Biosci. Biotechnol. Biochem. 76: 1173-1176. https://doi.org/10.1271/bbb.120045
  19. Liu P, Martino T, Opavsky MA, Penninger J. 1996. Viral myocarditis: balance between viral infection and immune response. Can. J. Cardiol. 12: 935-943.
  20. Martino TA, Liu P, Sole MJ. 1994. Viral infection and the pathogenesis of dilated cardiomyopathy. Circ. Res. 74: 182-188. https://doi.org/10.1161/01.RES.74.2.182
  21. Schnitzler P, Neuner A, Nolkemper S, Zundel C, Nowack H, Sensch KH, Reichling J. 2010. Antiviral activity and mode of action of propolis extracts and selected compounds. Phytother. Res. 24 Suppl 1: S20-S28. https://doi.org/10.1002/ptr.2868
  22. Song JH, Kwon BE, Jang H, Kang H, Cho S, Park K, et al. 2015. Antiviral activity of chrysin derivatives against coxsackievirus B3 in vitro and in vivo. Biomol. Ther. (Seoul) 23: 465-470. https://doi.org/10.4062/biomolther.2015.095
  23. Sun F, Li Y, Jia T, Ling Y, Liang L, Liu G, et al. 2012. Differential expression of coxsackievirus and adenovirus receptor on alveolar epithelial cells between fetal and adult mice determines their different susceptibility to coxsackievirus B infection. Arch. Virol. 157: 1101-1111. https://doi.org/10.1007/s00705-012-1254-6
  24. Wang SM, Liu CC. 2014. Update of enterovirus 71 infection: epidemiology, pathogenesis and vaccine. Expert Rev. Anti Infect. Ther. 12: 447-456. https://doi.org/10.1586/14787210.2014.895666
  25. Wong J, Zhang J, Yanagawa B, Luo Z, Yang X, Chang J, et al. 2012. Cleavage of serum response factor mediated by enteroviral protease 2A contributes to impaired cardiac function. Cell Res. 22: 360-371. https://doi.org/10.1038/cr.2011.114
  26. Woodruff JF. 1980. Viral myocarditis. A review. Am. J. Pathol. 101: 425-484.
  27. Xiong D, Lee GH, Badorff C, Dorner A, Lee S, Wolf P, Knowlton KU. 2002. Dystrophin deficiency markedly increases enterovirus-induced cardiomyopathy: a genetic predisposition to viral heart disease. Nat. Med. 8: 872-877. https://doi.org/10.1038/nm737
  28. Xiong D, Yajima T, Lim BK, Stenbit A, Dublin A, Dalton ND, et al. 2007. Inducible cardiac-restricted expression of enteroviral protease 2A is sufficient to induce dilated cardiomyopathy. Circulation 115: 94-102.
  29. Yu J, Sun L, Zhou L, Luo X, Guo J, Liu C, Cong P. 1997. [Chemical constituents of fructus Amomi]. Zhongguo Zhong Yao Za Zhi 22: 231-232, 255.
  30. Yun SH, Lee WG, Kim YC, Ju ES, Lim BK, Choi JO, et al. 2012. Antiviral activity of coxsackievirus B3 3C protease inhibitor in experimental murine myocarditis. J. Infect. Dis. 205: 491-497. https://doi.org/10.1093/infdis/jir745

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