Skip to main content
SpringerLink
Log in

Antiviral effects of Phyllanthus urinaria containing corilagin against human enterovirus 71 and Coxsackievirus A16 in vitro

  • Research Article
  • Published:
Archives of Pharmacal Research Aims and scope Submit manuscript

Abstract

Human enterovirus 71 (EV71) and Coxsackievirus A16 (CA16) are major causative agents of hand, foot, and mouth disease (HFMD) especially in infants and children under 5 years of age. Despite recent outbreaks of HFMD, there are no approved therapeutics against EV71 and CA16 infection. Moreover, in a small percentage of cases, the disease progression can lead to serious complications of the central nervous system. In this study, we investigated the antiviral effect of corilagin and Phyllanthus urinaria extract, which contains corilagin as a major component, on EV71 and CA16 infection in vitro. Our results indicate that corilagin reduces the cytotoxicity induced by EV71 or CA16 on Vero cells with and IC50 value of 5.6 and 32.33 μg/mL, respectively. We confirmed the presence of corilagin in EtOAc and BuOH fractions from P. urinaria extract and this correlated with antiviral activity of the fractions against EV71 or CA16. Future studies will be required to confirm the antiviral activity of corilagin and P. urinaria extract in vivo. Challenging a model with a lethal dose of viral infection will be required to test this. Collectively, our work provides potential candidates for the development of novel drugs to treat HFMD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • Chen, Y., and C. Chen. 2011. Corilagin prevents tert-butyl hydroperoxide-induced oxidative stress injury in cultured n9 murine microglia cells. Neurochemistry International 59(2): 290–296.

    Article  CAS  PubMed  Google Scholar 

  • Cheng, A., C.P. Fung, C.C. Liu, Y.T. Lin, H.Y. Tsai, S.C. Chang, A.H. Chou, J.Y. Chang, R.H. Jiang, Y.C. Hsieh, I.J. Su, et al. 2013. A phase I, randomized, open-label study to evaluate the safety and immunogenicity of an enterovirus 71 vaccine. Vaccine 31(20): 2471–2476.

    Article  CAS  PubMed  Google Scholar 

  • Choi, H.J., J.H. Kim, C.H. Lee, Y.J. Ahn, J.H. Song, S.H. Baek, and D.H. Kwon. 2009a. Antiviral activity of quercetin 7-rhamnoside against porcine epidemic diarrhea virus. Antiviral Research 81(1): 77–81.

    Article  CAS  PubMed  Google Scholar 

  • Choi, H.J., J.H. Song, K.S. Park, and D.H. Kwon. 2009b. Inhibitory effects of quercetin 3-rhamnoside on influenza a virus replication. European Journal of Pharmaceutical Sciences 37(3–4): 329–333.

    Article  CAS  PubMed  Google Scholar 

  • Duan, W., Y. Yu, and L. Zhang. 2005. Antiatherogenic effects of Phyllanthus emblica associated with corilagin and its analogue. Yakugaku Zasshi 125(7): 587–591.

    Article  CAS  PubMed  Google Scholar 

  • Guo, Y.J., L. Zhao, X.F. Li, Y.W. Mei, S.L. Zhang, J.Y. Tao, Y. Zhou, and J.H. Dong. 2010. Effect of corilagin on anti-inflammation in HSV-1 encephalitis and HSV-1 infected microglias. European Journal of Pharmacology 635(1–3): 79–86.

    Article  CAS  PubMed  Google Scholar 

  • Hau, D.K., G.Y. Zhu, A.K. Leung, R.S. Wong, G.Y. Cheng, P.B. Lai, S.W. Tong, F.Y. Lau, K.W. Chan, W.Y. Wong, K.H. Lam, et al. 2010. In vivo anti-tumour activity of corilagin on hep3b hepatocellular carcinoma. Phytomedicine 18(1): 11–15.

    Article  CAS  PubMed  Google Scholar 

  • Jikai, L., H. Yue, T. Henkel, and K. Weber. 2002. One step purification of corilagin and ellagic acid from Phyllanthus urinaria using high-speed countercurrent chromatography. Phytochemical Analysis 13(1): 1–3.

    Article  CAS  PubMed  Google Scholar 

  • Kinoshita, S., Y. Inoue, S. Nakama, T. Ichiba, and Y. Aniya. 2007. Antioxidant and hepatoprotective actions of medicinal herb, terminalia catappa L. From okinawa island and its tannin corilagin. Phytomedicine 14(11): 755–762.

    Article  CAS  PubMed  Google Scholar 

  • Li, Y., S. Yu, D. Liu, P. Proksch, and W. Lin. 2012. Inhibitory effects of polyphenols toward HCV from the mangrove plant excoecaria agallocha L. Bioorganic Medicinal Chemistry Letters 22(2): 1099–1102.

    Article  CAS  PubMed  Google Scholar 

  • Lin, S.Y., C.C. Wang, Y.L. Lu, W.C. Wu, and W.C. Hou. 2008. Antioxidant, anti-semicarbazide-sensitive amine oxidase, and anti-hypertensive activities of geraniin isolated from Phyllanthus urinaria. Food and Chemical Toxicology 46(7): 2485–2492.

    Article  CAS  PubMed  Google Scholar 

  • Lin, L.T., T.Y. Chen, C.Y. Chung, R.S. Noyce, T.B. Grindley, C. McCormick, T.C. Lin, G.H. Wang, C.C. Lin, and C.D. Richardson. 2011. Hydrolyzable tannins (chebulagic acid and punicalagin) target viral glycoprotein-glycosaminoglycan interactions to inhibit herpes simplex virus 1 entry and cell-to-cell spread. Journal of Virology 85(9): 4386–4398.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lin, L.T., T.Y. Chen, S.C. Lin, C.Y. Chung, T.C. Lin, G.H. Wang, R. Anderson, C.C. Lin, and C.D. Richardson. 2013. Broad-spectrum antiviral activity of chebulagic acid and punicalagin against viruses that use glycosaminoglycans for entry. BMC Microbiology 13: 187.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Liu, K.C., M.T. Lin, S.S. Lee, J.F. Chiou, S. Ren, and E.J. Lien. 1999. Antiviral tannins from two phyllanthus species. Planta Medica 65(1): 43–46.

    Article  CAS  PubMed  Google Scholar 

  • Mao, Q., Wang, Y., Yao, X., Bian, L., Wu, X., Xu, M., Liang, Z. 2013. Coxsackievirus a16: epidemiology, diagnosis, and vaccine. Human Vaccines Immunotherapeutics 10(2): 360–367.

    Google Scholar 

  • Moreira, J., L.C. Klein-Junior, V. Cechinel Filho, and F. de Campos Buzzi. 2013. Anti-hyperalgesic activity of corilagin, a tannin isolated from Phyllanthus niruri L. (euphorbiaceae). Journal of Ethnopharmacology 146(1): 318–323.

    Article  CAS  PubMed  Google Scholar 

  • Notka, F., G. Meier, and R. Wagner. 2004. Concerted inhibitory activities of Phyllanthus amarus on HIV replication in vitro and ex vivo. Antiviral Research 64(2): 93–102.

    CAS  PubMed  Google Scholar 

  • Park, J.H., H.S. Joo, K.Y. Yoo, B.N. Shin, I.H. Kim, C.H. Lee, J.H. Choi, K. Byun, B. Lee, S.S. Lim, M.J. Kim, et al. 2011. Extract from terminalia chebula seeds protect against experimental ischemic neuronal damage via maintaining SODs and BDNF levels. Neurochemical Research 36(11): 2043–2050.

    Article  CAS  PubMed  Google Scholar 

  • Patel, J.R., P. Tripathi, V. Sharma, N.S. Chauhan, and V.K. Dixit. 2011. Phyllanthus amarus: ethnomedicinal uses, phytochemistry and pharmacology: a review. Journal of Ethnopharmacology 138(2): 286–313.

    Article  CAS  PubMed  Google Scholar 

  • Satomi, H., K. Umemura, A. Ueno, T. Hatano, T. Okuda, and T. Noro. 1993. Carbonic anhydrase inhibitors from the pericarps of punica granatum L. Biological Pharmaceutical Bulletin 16(8): 787–790.

    Article  CAS  PubMed  Google Scholar 

  • Shiota, S., M. Shimizu, J. Sugiyama, Y. Morita, T. Mizushima, and T. Tsuchiya. 2004. Mechanisms of action of corilagin and tellimagrandin I that remarkably potentiate the activity of beta-lactams against methicillin-resistant staphylococcus aureus. Microbiology and Immunology 48(1): 67–73.

    Article  CAS  PubMed  Google Scholar 

  • Solomon, T., P. Lewthwaite, D. Perera, M.J. Cardosa, P. McMinn, and M.H. Ooi. 2010. Virology, epidemiology, pathogenesis, and control of enterovirus 71. The Lancet Infectious Diseases 10(11): 778–790.

    Article  PubMed  Google Scholar 

  • Tan, C.W., Y.F. Chan, K.M. Sim, E.L. Tan, and C.L. Poh. 2012. Inhibition of enterovirus 71 (ev-71) infections by a novel antiviral peptide derived from EV-71 capsid protein vp1. PLoS One 7(5): e34589.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Thitilertdecha, N., A. Teerawutgulrag, J.D. Kilburn, and N. Rakariyatham. 2010. Identification of major phenolic compounds from nephelium lappaceum 1. And their antioxidant activities. Molecules (Basel, Switzerland) 15(3): 1453–1465.

    Article  CAS  Google Scholar 

  • Yang, Y., J. Xiu, L. Zhang, C. Qin, and J. Liu. 2012a. Antiviral activity of punicalagin toward human enterovirus 71 in vitro and in vivo. Phytomedicine 20(1): 67–70.

    Article  PubMed  Google Scholar 

  • Yang, Y., L. Zhang, X. Fan, C. Qin, and J. Liu. 2012b. Antiviral effect of geraniin on human enterovirus 71 in vitro and in vivo. Bioorganic Medicinal Chemistry Letters 22(6): 2209–2211.

    Article  CAS  PubMed  Google Scholar 

  • Yang, Y., J. Xiu, J. Liu, L. Zhang, X. Li, Y. Xu, and C. Qin. 2013. Chebulagic acid, a hydrolysable tannin, exhibited antiviral activity in vitro and in vivo against human enterovirus 71. International Journal of Molecular Sciences 14(5): 9618–9627.

    Article  PubMed Central  PubMed  Google Scholar 

  • Yuandani, M. Ilangkovan, I. Jantan, H.F. Mohamad, K. Husain, and A.F. Abdul Razak. 2013. Inhibitory effects of standardized extracts of Phyllanthus amarus and Phyllanthus urinaria and their marker compounds on phagocytic activity of human neutrophils. Evidence-Based Complementary and Alternative Medicine 2013: 603634. doi:10.1155/2013/603634

  • Zhao, L., S.L. Zhang, J.Y. Tao, R. Pang, F. Jin, Y.J. Guo, J.H. Dong, P. Ye, H.Y. Zhao, and G.H. Zheng. 2008. Preliminary exploration on anti-inflammatory mechanism of corilagin (beta-1-o-galloyl-3,6-(r)-hexahydroxydiphenoyl-d-glucose) in vitro. International Immunopharmacology 8(7): 1059–1064.

    Article  CAS  PubMed  Google Scholar 

  • Zheng, Z., H. Li, Z. Zhang, J. Meng, D. Mao, B. Bai, B. Lu, P. Mao, Q. Hu, and H. Wang. 2011. Enterovirus 71 2c protein inhibits tnf-alpha-mediated activation of nf-kappab by suppressing ikappab kinase beta phosphorylation. Journal of immunology (Baltimore, Md : 1950) 187(5): 2202–2212.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by a grant from R&D project (2013-NG48001-00) at Korea National Institute of Health. This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MEST) (No. 2011-0009018).

Author information

Authors and Affiliations

  1. College of Pharmacy, Kangwon National University, Hyoja 2-dong, Chuncheon-si, Gangwon-do, 200-701, South Korea

    Jae Hyoung Song, Eun-Hye Hong, Bo-Ra Lee, Yong Soo Kwon & Hyun-Jeong Ko

  2. Division of Vaccine Research, Center for Infectious Diseases, National Institute of Health, Korea Centers for Diseases Control and Prevention, Cheongwon-gun, Chungcheongbukdo, Korea

    Sang-Gu Yeo, Jae Hyoung Song & Sang won Lee

  3. Laboratory Animal Medicine, College of Veterinary Medicine, Seoul National University, Seoul, South Korea

    Sang-Gu Yeo & Jae-Hak Park

  4. College of Pharmacy, Ajou University, Suwon, Kyeonggi-do, Korea

    Sun-Young Chang

  5. College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon, 406-840, Korea

    Seung Hyun Kim

Authors
  1. Sang-Gu Yeo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jae Hyoung Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Eun-Hye Hong
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bo-Ra Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yong Soo Kwon
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sun-Young Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Seung Hyun Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Sang won Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jae-Hak Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Hyun-Jeong Ko
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hyun-Jeong Ko.

Additional information

Sang-Gu Yeo, Jae Hyoung Song, Jae-Hak Park, Hyun-Jeong Ko equally contributed to this paper.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yeo, SG., Song, J.H., Hong, EH. et al. Antiviral effects of Phyllanthus urinaria containing corilagin against human enterovirus 71 and Coxsackievirus A16 in vitro. Arch. Pharm. Res. 38, 193–202 (2015). https://doi.org/10.1007/s12272-014-0390-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12272-014-0390-9

Keywords

Search

Navigation