약학회지 (YAKHAK HOEJI)

  • 제49권4호
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  • Pages.323-329
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  • 2005
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  • 0377-9556(pISSN)
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  • 2383-9457(eISSN)
대한약학회 (The Pharmaceutical Society of Korea)
권호 표지

황련에서 분리된 단백질성분의 항진균효과

Anticandidal Activity of the Protein Substance from Coptidis Rhizoma

  • 김현경 (동덕여자대학교 약학대학 면역 미생물학교실) ;
  • 이주희 (동덕여자대학교 약학대학 면역 미생물학교실) ;
  • 심진기 (한국생산기술연구원) ;
  • 한용문 (동덕여자대학교 약학대학 면역 미생물학교실)
  • 발행 : 2005.08.01
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초록

Antimicrobial peptides are evolutionary ancient weapons for animal and plant species to depend themselves against infectious microbes. In the present study, we investigated if an antimicrobial peptide was produced from Coptidis Rhizoma. For the determination, protein substance from the medicinal plant was isolated by various preparations. Among the preparations, the protein portion dissolved in phosphate-buffered saline solution (CRP-DS) that contained the most amount of protein $(90\%)$ resulted in maximal inhibition of Candida albicans which causes local and systemic infections. Analyses by gel-electrophoresis and gel-permeation chromatography showed the CRP-DS formed a single band of approximately 11.8 KDa as molecular size. Antifungal activity of the CRP-DS was almost equivalent to antifungal activity by fluconazole, resulting in MIC (minimal inhibitory concentration) of approximately $50{\mu}g/ml$. The antifungal activity was a dose-dependent. The antifungal activity appeared to be inactivated by heat-treatment and ionic strength, respectively. In a murine model, the CRP-DS enhanced resistance of mice against disseminated candidiasis. The HPLC analysis demonstrated maximum $4\%$ of berberine as residual content in the CRP-DS preparation resulted in no influence on the antifungal activity. In addition, protein portion isolated from Phellodendri Cortex producing the alkaloid component like Coptidis Rhizoma had no such anticandidal effect. These results indicate that the protein substance from Coptidis Rhizoma was responsible for the antifungal activity.

키워드

참고문헌

  1. Han, Y., Kozel, T. R., Zhang, M. X., MacGill, R. S., Carroll, M. C. and Cutler, J. E. : Complement is essential for protection by an IgM and an IgG3 monoclonal antibody against experimental, hematogenously disseminated candidiasis. J. Immunol. 167, 1550 (2001) https://doi.org/10.4049/jimmunol.167.3.1550
  2. Wisplinghoff, H., Bischoff, T., Tallent, S. M., Seifert H., Wenzel, R. P. and Edmond, M. B. : Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide survelliance study. Clin. Infect. Dis. 39(3), 309 (2004) https://doi.org/10.1086/421946
  3. Loeffler, J. and Stevens, D. A. : Antifungal drug resistance. Clin. Infect. Dis. 15(Suppl. 1), S31 (2003)
  4. Perfect, J. R and Schell, W. A. : The new fungal opportunists are coming. Clin. Infect. Dis. 22(Suppl. 2), S112 (1996)
  5. Villar, C. C., Kashleva, H. and Dongari-Bagtzoglou, A. : Role of Candida albicans polymorphism in interactions with oral epithelial cells. Oral. Microbiol. Immunol. 19(4), 262 (2004) https://doi.org/10.1111/j.1399-302X.2004.00150.x
  6. Vazquez-Torres, A. and Balish, E. : Macrophages in resistance to candidiasis. Microbiol. Mol. Biol. Rev. 61(2), 170 (1997)
  7. Ashman, R. B. and Papadimitriou, J. M. : What's new in the mechanisms of host resistance to Candida albicans infection? Pathol. Res. Pract. 186(4), 527 (1990) https://doi.org/10.1016/S0344-0338(11)80477-2
  8. Odds, F. C., Brown, A. J. and Gow, N. A. : Antifungal agents: mechanisms of action. Trends Microbiol. 11(6), 272 (2003) https://doi.org/10.1016/S0966-842X(03)00117-3
  9. Conly, J., Rennie, R, Johnson, J., Farah, S. and Hellman, L. : Disseminated candidacies due to amphotericin B resistant Candida albicans. J. Infect. Dis. 165, 761 (1992) https://doi.org/10.1093/infdis/165.4.761
  10. Cuenca-Estrella, M., Mellado, E., Guerra, T. M., Monzon, A. and Rodriguez-Tudela, J. L. : Susceptibility of fluconazoleresistant clinical isolates of Candida spp. to echinocandin LY303366, itraconazole and amphotericin B. J. Antimicrob. Chemother. 46, 475 (2000) https://doi.org/10.1093/jac/46.3.475
  11. Defever, K. S., Whelan, W. L., Rogers, A. L., Beneke, E. S., Veselenak, J. M. and Soll, D R. : Candida albicans resistance to 5-fluorocytosine: frequency of partially resistant strains among clinical isolates. Antimicrob. Agents Chemother. 22, 810 (1982) https://doi.org/10.1128/AAC.22.5.810
  12. Hernandez, S., Lopez-Ribot, J. L., Najvar, L. K., McCarthy, D. I., Bocanegra, R. and Graybill, J. R. : Caspofungin resistance in Candida albicans: correlating clinical outcome with laboratory susceptibility testing of three isogenic isolates serially obtained from a patient with progressive Candida esophagitis. Antimicrob. Agents Chemother. 48(4), 1382 (2004) https://doi.org/10.1128/AAC.48.4.1382-1383.2004
  13. Avrahami, D. and Shai, Y. : A new group of antifungal and antibacterial lipopeptides derived from non-membrane active peptides conjugated to palmitic acid. J. Biol. Chem. 279(13), 12277 (2004) https://doi.org/10.1074/jbc.M312260200
  14. Han, Y., Morrison, R. P. and Cutler, J. E. : A vaccine and monoclonal antibodies that enhance mouse resistance to Candida albicans vaginal infection. Infect. Immun. 66(12), 5771 (1998)
  15. Han, Y., Ulrich, M. A. and Cutler, J. E. : Candida albicans mannan extract-protein conjugates induce a protective immune response against experimental candidiasis. J. Infect. Dis. 179(6), 1477 (1999) https://doi.org/10.1086/314779
  16. Han, Y. and Cutler, J. E. : Antibody response that protects against disseminated candidiasis. Infect. Immun. 63(7), 2714 (1995)
  17. Han, Y., Riesselman, M. H. and Cutler, J. E. : Protection against candidiasis by an immunoglobulin G3 (IgG3) monoclonal antibody specific for the same mannotriose as an IgM protective antibody. Infect. Immun. 68(3), 1649 (2000) https://doi.org/10.1128/IAI.68.3.1649-1654.2000
  18. Han, Y. and Cutler, J. E. : Assessment of a mouse model of neutropenia and the effect of an anti-candidiasis monoclonal antibody in these animals. J. Infect. Dis. 175(5), 1169 (1997) https://doi.org/10.1086/516455
  19. Lupetti, A., Nibbering, P. H, Campa, M., Del Tacca, M. and Danesi, R. : Molecular targeted treatments for fungal infections: the role of drug combinations. Trends. Mol. Med. 9(6), 269 (2003) https://doi.org/10.1016/S1471-4914(03)00091-1
  20. McCutcheon, A. R., Ellis, S. M., Hancock, R. E. and Towers, G. H. : Antibiotic screening of medicinal plants of the British Columbian native peoples. J. Ethnopharmacol. 37(3),213 (1992) https://doi.org/10.1016/0378-8741(92)90036-Q
  21. Gibson, B. W., Poulter, L., Williams, D. H. and Maggio, J. E. : Novel peptide fragments originating from PGLa and the caerulein and xenopsin precursors from Xenopus laevis. J. Biol. Chem. 261(12), 5341 (1986)
  22. Jasir, A., Kasprzykowski, F., Lindstrom, V., Schalen, C. and Grubb, A. : New antimicrobial peptide active against Grampositive pathogens. Indian. J. Med. Res. 119(Suppl), 74 (2004)
  23. Giacometti, A., Cirioni, O., Greganti, G., Quarta, M. amd Scalise, G. : In vitro activities of membrane-active peptides against gram-positive and gram-negative aerobic bacteria. Antimicrob. Agents Chemother. 42(12), 3320 (1998)
  24. Nibbering, P. H., Ravensbergen, E., Welling, M. M., van Berkel, L. A., van Berkel, P. H., Pauwels, E. K. and Nuijens, J. H. : Human lactoferrin and peptides derived from its N terminus are highly effective against infections with antibioticresistant bacteria. Infect. Immun. 69(3), 1469 (2001) https://doi.org/10.1128/IAI.69.1.1-8.2001
  25. Moore, A. J., Beazley, W. D., Bibby, M. C. and Devine, D. A. : Antimicrobial activity of cecropins. J. Antimicrob. Chemother. 37(6), 1077 (1996) https://doi.org/10.1093/jac/37.6.1077
  26. Zhang, L., Yu, W, He, T., Yu, J., Caffrey, R. E., Dalmasso, E. A., Fu, S., Pham, T., Mei, J., Ho, J. J., Zhang, W, Lopez, P. and Ho, D. D. : Contribution of human alpha-defensin 1, 2, and 3 to the anti-HIV-1 activity of CD8 antiviral factor. Science 298(5595), 995 (2002) https://doi.org/10.1126/science.1076185
  27. Robinson, W E. Jr., McDougall, B., Tran, D. and Selsted, M. E. : Anti-HIV-1 activity of indolicidin, an antimicrobial peptide from neutrophils. J. Leukoc. Biol. 63(1), 94 (1998) https://doi.org/10.1002/jlb.63.1.94
  28. Edgerton, M., Koshlukova, S. E., Araujo, M. W, Patel, R. C., Dong, J. and Bruenn, J. A. : Salivary histatin 5 and human neutrophil defensin 1 kill Candida aibicans via shared pathways. Antimicrob. Agents Chemother. 44(12), 3310 (2002) https://doi.org/10.1128/AAC.44.12.3310-3316.2000
  29. De Lucca, A. J. and Walsh, T. J. : Antifungal peptides: novel therapeutic compounds against emerging pathogens. Antimicrob. Agents Chemother. 43(1), 1 (1999) https://doi.org/10.1093/jac/43.1.1
  30. Fujimura, M., Ideguchi, M., Minami, Y., Watanabe, K. and Tadera, K. : Amino acid sequence and antimicrobial activity of chitin-binding peptides, Pp-AMP 1 and Pp-AMP 2, from Japanese bamboo shoots (Phyllostachys pubescens). Biosci. Biotechnol. Biochem. 69(3), 642 (2005) https://doi.org/10.1271/bbb.69.642
  31. Broekaert, W. F., Terras, F. R., Cammue, B. P. and Osborn, R. W. : Plant defensins: novel antimicrobial peptides as components of the host defense system. Plant Physiol. 108(4), 1353 (1995) https://doi.org/10.1104/pp.108.4.1353
  32. Tauszig, S., Jouanguy, E., Hoffmann, J. A. and Imler, J. L. : Toll-related receptors and the control of antimicrobial peptide expression in Drosophila. Proc. Natl. Acad Sci. USA 97(19), 10520 (2000)
  33. Vora, P., Youdim, A., Thomas, L. S., Fukata, M., Tesfay, S. Y., Lukasek, K., Michelsen, K. S., Wada, A., Hirayama, T., Arditi, M. and Abreu, M. T. : Beta-defensin-2 expression is regulated by TLR signaling in intestinal epithelial cells. J. Immunol. 173(9), 5398 (2004) https://doi.org/10.4049/jimmunol.173.9.5398
  34. Freile, M. L., Giannini, E, Pucci, G., Sturniolo, A., Rodero, L., Pucci, O., Balzareti, V. and Enriz, R. D. : Antimicrobial activity of aqueous extracts and of berberine isolated from Berberis heterophylla. Fitoterapia. 74(7-8), 702 (2003) https://doi.org/10.1016/S0367-326X(03)00156-4
  35. Stermitz, F. R., Lorenz, P., Tawara, J. N., Zenewicz, L. A. and Lewis, K. : Synergy in a medicinal plant: antimicrobial action of berberine potentiated by 5'-methoxyhydnocarpin, a multidrug pump inhibitor. Proc. Natl. Acad Sci. USA 97(4), 1433 (2002)
  36. [No authors listed] Berberine : Altern. Med. Rev. 5(2), 175 (2000).
  37. Han, Y. : Berberine synergy with amphotericin B against growth of Candida albicans. Dongduk Pharml. Res. 6(6), 49 (2002)
  38. Cutler, J. E., Granger, B. and Han, Y. : Candida and Candidosis. ASM Press, Washington, D.C. pp. 243-256 (2003)
  39. Han, Y. and Lee, J. H. : Berberine synergy with amphotericin B against disseminated candidiasis in mice. Biol. Pharm. Bull. 28(3), 541 (2005) https://doi.org/10.1248/bpb.28.541
  40. Han, Y. and Lee, J. H. : A pneumococcal conjugate vaccine formula induces protection in mice against disseminated disease due to Streptococcus pneumoniae. J. Pharm. Soc. Korea 48(6), 345 (2004)
  41. Rex, J. H., Pfaller, M. A., Lancaster, M., Odds, F. C., Bolmstrom, A. and Rinaldi, M. G. : Quality control guidelines for National Committee for Clinical Laboratory Standards-recommended broth macrodilution testing of ketoconazole and itraconazole. J. Clin. Microbiol. 34(4), 816 (1996)
  42. Brogden, K. A. : Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria? Nat. Rev. Microbiol. 3(3), 238 (2005) https://doi.org/10.1038/nrmicro1079