Food Science and Preservation (한국식품저장유통학회지)

The Korean Society of Food Preservation (한국식품저장유통학회)
권호 표지
DOI QR코드

DOI QR Code

Antiviral activity of methanol extract from Ephedra sinica Stapf

마황 추출물의 항바이러스 활성

  • Lee, Doseung (Jeju Biodiversity Research Institute (JBRI), Jeju Technopark) ;
  • Lee, Dong-Sun (College of Applied Life Science (SARI), Jeju National University)
  • 이도승 ((재)제주테크노파크 생물종다양성연구소) ;
  • 이동선 (제주대학교 생명공학부)
  • Received : 2013.11.26
  • Accepted : 2014.02.04
  • Published : 2014.10.30
Download PDF
⟨ Previous Next ⟩

Abstract

Ephedra sinica Stapf, known as a medicinal plant, inhibited not only syncytium formation, but also trafficking of viral glycoprotein, hemagglutinin-neuramidase (HN) to the cell-surface. Trafficking of viral glycoprotein to the surface of infected-cells results in syncytium formation in Newcastle disease virus (NDV)-infected baby hamster kidney (BHK) cells. Viral glycoprotein in the infected-cell is processed within the endoplasmic reticulum during routing into surface. The processing of viral glycoprotein like a N-linked oligosaccharide trimming by ${\alpha}$-glucosidase in cell is necessary for virus infection. Methanol extracts showed inhibitory activities ($IC_{50}$ $15{\mu}g/mL$) against ${\alpha}$-glucosidase. This suggested that E. sinica extracts inhibited the cell-surface expression of NDV-HN glycoprotein without significantly affecting HN glycoprotein synthesis in NDV-infected BHK cells.

Newcastle disease virus(NDV) 감염된 baby hamster kidney(BHK) 세포에서 syncytium(합포체) 형성은 세포막 표면으로의 수송된 바이러스 당단백질 hemagglutinin-neuramidase(HN)에 의해 일어난다. HAU 값은 추출물의 농도가 25과 3.2 ug/mL 사이에서는 현저하게 감소하였으나, NDV 감염된 HAD(%)는 25 ug/mL 농도에서 광범위한 흡착능의 감소를 나타내 바이러스 당단백질의 세포내 생합성은 저해되지 않았다. 그러므로, 약용식물인 마황 메탄올 추출물이 바이러스 당단백질의 세포막으로의 수송과 함께 합포체 형성을 저해하여 항바이러스 작용을 하였다. 또한 마황 추출물의 저해활성을 조사한 결과 ${\alpha}$-glucosidase에 대한 추출물의 $IC_{50}$은 $18{\mu}g/mL$이었으며, ${\beta}$-glucosidase, ${\alpha}$-mannosidase, ${\beta}$-mannosidase에 대한 마황 추출물의 $IC_{50}$은 각각 60, 40, $150{\mu}g/mL$로 나타나 ${\beta}$-type glycosidases 보다 ${\alpha}$-type glycosidase에 대한 효소활성 저해능이 우수하였다. 따라서 $IC_{50}$농도에서는 세포내에서 당단백질 생합성은 저해되지 않으며 당단백질의 수송을 저해하는 것으로 판단되었으며 향후 항바이러스 관련 작용기작의 연구가 필요하다고 판단된다.

Keywords

References

  1. Abourashed E, El-Alfy A, Khan I, Walker L (2003) Ephedra in perspective - a current review. Phytother Res, 17, 703-712 https://doi.org/10.1002/ptr.1337
  2. Huang KC (1993) The Pharmacology of Chinese Herbs; CRC Press Inc. Boca Raton, FL, USA, p 229-232
  3. Erdelmeier CA, Cinatl J Jr, Rabenau H, Doerr HW, Biber A, Koch E (1996) Antiviral and antiphlogistic activities of Hamamelis virginiana Bark. Planta Med, 62, 241–245 https://doi.org/10.1055/s-2006-957868
  4. De Bruyne T, Pieters L, Witvrouw M, de Clercq E, Vanden Berghe D, Vlietinck J (1999) Biological evaluation of proanthocyanidin dimers and related polyphenols. J Nat Prod, 62, 954–958 https://doi.org/10.1021/np980481o
  5. Takechi M, Tanaka Y, Takehara M, Nonaka GI, Nishioka I (1985) Structure and antiherpetic activity among the tannins. Phytochem, 24, 2245–2250 https://doi.org/10.1016/S0031-9422(00)83018-6
  6. Fukuchi K, Sakagami H, Okuda T, Hatano T, Tanuma S (1989) Inhibition of herpes simplex virus infection by tannins and related compounds. Antiviral Res, 11, 285–297 https://doi.org/10.1016/0166-3542(89)90038-7
  7. Abourashed EA, El-Alfy AT, Khan IA, Walker L (2003) Ephedra in perspective-a current review. Phytother Res, 17, 703-712 https://doi.org/10.1002/ptr.1337
  8. Dennis JW, Laferte S, Waghorne C, Breitman ML, Kerbel RS(1987) Beta 1-6 branching of Asn-linked oligosaccharides is directly associated with metastasis. Science, 236, 582-585 https://doi.org/10.1126/science.2953071
  9. Lee DS, Lee JM, Kim SU, Chang KT, Lee SH (2007) Ceftezole, a cephem antibiotic, is and $\alpha$-glucosidase inhibitor with in vivo anti-diabetic activity. Int J Mol Med, 20, 379-383
  10. Mehta A, Zitzmann N, Rudd PM, Block TM, Dwek RA (1998) $\alpha$-Glucosidase inhibitors as potential broad based anti-viral agents. FEBS Lett, 430, 17-22 https://doi.org/10.1016/S0014-5793(98)00525-0
  11. Goss PE, Baker MA, Carver JP, Dennis JW (1995) Inhibitors of carbohydrate processing: A new class of anticancer agents. Clin Cancer Res, 1, 935-944
  12. van de Laar FA, Lucassen PL, Akkermans RP, van de Lisdonk EH, Rutten GE, van Weel C (2005) Alpha-glucosidase inhibitors for patients with type 2 diabetes: Results from a Cochrane systematic review and meta-analysis. Diabetes Care, 28, 154-163 https://doi.org/10.2337/diacare.28.1.154
  13. Courageot MP, Frenkiel MP, Duarte Dos Santos C, Deubel V, Despres P (2000) $\alpha$-Glucosidase inhibitors reduce dengue virus production by affecting the initial steps of virion morphogenesis in the endoplasmic reticulum. J Virol, 74, 564-572 https://doi.org/10.1128/JVI.74.1.564-572.2000
  14. Dettenhofer M, Yu XF (2001) Characterization of the biosynthesis of human immunodeficiency virus Type 1 Env from infected T-cells and the effects of glucose trimming of Env on virion infectivity. J Biol Chem, 276, 5985-5991 https://doi.org/10.1074/jbc.M008933200
  15. Johnson VA, Walker BD, Barlow MA, Paradis TJ, Chou TC, Hirsch MS (1989) Synergistic inhibition of human immunodeficiency virus type 1 and type 2 replication in vitro by castanospermine and 3'-azido-3'-deoxythymidine. Antimicrob Agents Ch, 3, 53-57
  16. Tsujii E, Muroi M, Shiragami N, Takatsuki A (1996) Nectrisine is a potent inhibitor of $\alpha$-glucosidases, demonstrating activities similarly at enzyme and cellular levels. Biochem Bioph Res Co, 220, 459-466 https://doi.org/10.1006/bbrc.1996.0427
  17. Papandreou MJ, Barbouche R, Guieu R, Kieny MP, Fenouillet E (2002) The $\alpha$-glucosidase inhibitor 1-deoxynojirimycin blocks human immunodeficiency virus envelope glycoprotein-mediated membrane fusion at the CXCR4 binding step. Mol Pharmacol, 61, 186-193 https://doi.org/10.1124/mol.61.1.186
  18. Fischer PB, Collin M, Karlsson GB, James W, Butters TD, Davis SJ, Gordon S, Dwek RA, Platt FM (1995) The $\alpha$-glucosidase inhibitor Nbuthyldeoxynojirimycin inhibits human immunodeficiency virus entry at the level of post-CD4 binding. J Virol, 69, 5791-5797
  19. Gruters RA, Neefjes JJ, Tersmette M, de Goede RE, Tulp A, Huisman HG, Miedema F, Ploegh HL (1987) Interference with HIV induced syncytium formation and viral infectivity by inhibitors of trimming glucosidase. Nature, 330, 74-77 https://doi.org/10.1038/330074a0
  20. Quinn TC (2008). HIV epidemiology and the effects of antiviral therapy on long-term consequences. AIDS, 22 (Suppl 3), 7-12
  21. Einfeld D (1996) Maturation and assembly of retroviral glycoproteins. Curr Top Microbiol, 214, 133-176
  22. Lee DS, Kim SC, Kim DH, Kim JH, Park SP, Riu YC, Kim MY, Cho SK, Riu KZ, Lee DS (2011) Screening of Phellinus linteus, a medicinal mushroom, for anti-viral activity. J Korean Soc Appl Biol Chem, 54, 475-478 https://doi.org/10.3839/jksabc.2011.073
  23. Kwon DH, Kim MB, Yoon DY, Lee YH, Kim JW, Lee HG, Choi IS, Lim JS, Choe YK (2003) Screening of plant resources of anti-viral activity. Korean J Medicinal Crop Sci, 1, 24-30
  24. Kang SY, Kim TG, Park MS, Han HM, Jung KK, Kang JH, Moon AR, Kim SH, (1999) Inhibitory effect of Eugenia caryophyllate, Ephedra sinica and cinnamomum cassia on the replication of HBV in HepG2.2.15 cells. J Appl Pharmacol, 7, 133-137
  25. Lee DS, Lee SH (2001) Genistein, a soy isoflavone, is a potent $\alpha$-glucosidase inhibitor. FEBS Lett, 501, 84-86 https://doi.org/10.1016/S0014-5793(01)02631-X
  26. Muroi M, Takasu A, Yamasaki M, Takatsuki A (1993) Folimycin (concanamycin A), an inhibitor of V-type H(+)-ATPase, blocks cell surface expression of virus-envelope glycoproteins. Biochem Bioph Res Co, 193, 999-1005 https://doi.org/10.1006/bbrc.1993.1724
  27. Lee JM, Kim JG, Kim TH, Lee DS, Kim JH, Cho SK, Riu KZ, Lee DS, Lee SH (2010) Nonactin hinders intracellular glycosylation in virus infected baby hamster kidney cells. Mol Med Rep, 3, 115-119
  28. Boo KH, Lee DS, Woo JK, Ko SH, Jeong EH, Hong Q, Riu KZ, Lee DS (2011) Anti-bacterial and anti-viral activity of extracts from Paeonia lactiflora roots. J Korean Soc Appl Biol Chem, 54, 132-135 https://doi.org/10.3839/jksabc.2011.020
  29. SAS (1998) SAS User's Guide: Statistics, 3th ed, SAS Institute Statistical Analysis System, Cary, NC, USA