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어성초 ethanol 추출물의 마우스 살모넬라 감염증에 대한 항균 및 치료효과 규명

Antibacterial and Therapeutic Effects of Houttuynia cordata Ethanol extract for Murine Salmonellosis

  • Kim, Dong-Hyeok (College of Veterinary Medicine, Gyeongsang National University) ;
  • Lim, Jung-Ju (College of Veterinary Medicine, Gyeongsang National University) ;
  • Lee, Jin-Ju (College of Veterinary Medicine, Gyeongsang National University) ;
  • Jung, Won-Chul (College of Veterinary Medicine, Gyeongsang National University) ;
  • Shin, Hyeon-Jin (College of Veterinary Medicine, Chungnam National University) ;
  • Lee, Hu-Jang (College of Veterinary Medicine, Gyeongsang National University) ;
  • Kim, Gon-Sup (College of Veterinary Medicine, Gyeongsang National University) ;
  • Kim, Suk (College of Veterinary Medicine, Gyeongsang National University)
  • 발행 : 2008.06.30

초록

항생제의 오남용으로 인한 항생제 내성을 가진 세균의 출현은 공중보건학적인 측면에서 많은 피해를 입히고 있다. 또한, 세포 내 기생세균의 경우 예방과 치료가 어려운 상황에 놓여져 있고 항생제 대체 물질개발에 많은 관심이 집중되고 있다. 어성초는 오랜 기간 동안 소독제, 이뇨제, 해열제, 항균제, 항바이러스 제제, 항염증 제제로서 사용되어왔으며 중요한 민간요법의 하나로서 인식되고 있는 바, 본 실험에서는 어성초의 ethanol 추출물이 세포내 기생 난치성 세균 감염증인 S. typhimurium의 감염증에 대한 치료효과를 검증하였다. 본 실험의 결과로서 HCEE 추출물이 탐식세포의 형태적 변화를 유도하였고, S. typhimurium에 대한 직접적인 살균작용과 탐식세포를 통한 항균작용은 미약한 것으로 나타났다. 또한 HCEE 추출물이 S. typhimurium의 탐식세포 감염 시 시간경과에 따라 감염능 및 세포내 증식능이 감소하는 것이 확인되었다. 탐식균에 의한 사멸을 유도하는 탐식세포의 NO의 산생량에 있어서는 HCEE 추출물의 처리가 탐식세포로부터 NO 산생이 감소되어 NO를 이용한 탐식세포의 균 사멸과는 직접적 연관이 없을 것으로 추정되며, 마우스 감염시험에서 HCEE를 투약이 상당한 치료효과를 나타내어 HCEE가 S. typhimurium에 의한 염증을 감소시키고, 또한 apoptosis를 유도함으로 인해 균을 제거함으로 이루어지는 것으로 추측된다. 본 연구를 통해 HCEE의 살모넬라증에 대한 치료효과를 확인 할 수 있었으며, 천연소재 약용자원을 활용한 난치성 세균 감염증에 대한 신약개발이 가능하고, 이의 활용은 항생제 오남용을 줄일 수 있고 국민보건 증진에 이바지 할 것이다.

Salmonellosis is a major bacterial zoonosis that causes a variety of disease syndromes, self-limited enteritis to fatal infection in animals and food-borne infection and typhoid fever in humans. Recently, the emergence of multidrug resistant strains of Salmonella spp. causes more serious problems in environment and public health. The present study was investigated the antibacterial effect of Houttuynia cordata ethanol extract(HCEE) for murine salmonellosis. In the cytotoxic effect of HCEE on RAW 264.7 cells, there was no detectable effect with any concentrations between 25 and 100 ${\mu}g/ml$ after 8 h incubation. The bacteriocidal effect of HCEE was not showed on a Salmonella enterica serovar Typhimurium(S. typhimurium). HCEE makes morphological change of the RAW 264.7 cells, and there was significant decreased bacterial uptake and intracellular replication within Salmonella infected cells. And further nitric oxide(NO) production of Salmonella infected RAW 264.7 cells with HCEE was decreased comparing to RAW 264.7 cells without HCEE until 8 h post infection. Oral administration of HCEE showed a therapeutic effect for S. typhimurium infected BALB/c mice. The mortality of HCEE treated mouse was 80% until 12 days, while that of HCEE untreated mouse was 100 % until 8 days after lethal dose of S. typhimurium infection. These data suggested that HCEE has a potency treatment for intracellular replicative pathogen including salmonellosis, brucellosis, tuberculosis, listeriosis etc., and the application of HCEE makes new strategies for safety medicine development without antibiotic resistance bacterial appearance and residue problem in food and solves the public health problem from antibiotic mis- and over use.

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참고문헌

  1. Tang, B. X., Duan, L. D., Wang, Y., Zhao, L. Z., Yu, Y. G. and Li, X. S. J. (2005) Shaoyang University (Natural Sciences) 2 (87), 80-81
  2. Zheng, Z. H., Dong, Z. H. and She, J. (1998) "Modern Research and Application of Traditional Chinese Medicines." Vol. 3. Xueyuan Press. Beijing. pp. 2983-3003
  3. Lu, H. M., Liang, Y. Z., Yi, L. Z. and Wu, X. J. (2006) Anti-inflammatory effect of Houttuynia cordata injection. J. Ethnopharmacol. 104, 245-249 https://doi.org/10.1016/j.jep.2005.09.012
  4. Lu, H., W, X., Liang, Y. and Zhang, J. (2006) Variation in chemical composition and antibacterial activities of essential oils from two species of Houttuynia THUNB. Chem. Pharm. Bull. 54(7), 936-40 https://doi.org/10.1248/cpb.54.936
  5. Iqbal, M., Ohen, R. I, Marzouk, K. and Liu, S. F., (2002) Time course of nitric oxide, peroxynitrite, and antioxidants in the endotoxemic heart. Crit. Care. Med. 30, 1291-1296 https://doi.org/10.1097/00003246-200206000-00021
  6. Berendji, D., Kolb-Bachofen, V., Meyer, K. L. and Kroncke, K.D., (1999) Influence of nitric oxide on the intracellular reduced glutathione pool: different cellular capacities and strategies to encounter nitric oxide-mediated stress. Free Radic. Biol. Med. 27, 773-780 https://doi.org/10.1016/S0891-5849(99)00123-9
  7. Park, E., Kum, S., Wang, C., Park, S. Y., Kim, B. S. and Schuller-Levis, G. (2005) Anti-inflammatory activity of herbal medicines: inhibition of nitric oxide production and tumor necrosis factor-alpha secretion in an activated macrophage-like cell line. Am. J. Chin. Med. 33(3), 415-424 https://doi.org/10.1142/S0192415X05003028
  8. Li, G. Z., Chai, O.H., Lee, M.S., Han, E.H., Kim H.T. and Song C.H. (2005) Inhibitory effects of Houttuynia cordata water extracts on anaphylactic reaction and mast cell activation. Biol. Pharm. Bull. 28(10), 1864-1868 https://doi.org/10.1248/bpb.28.1864
  9. Cherayil, B. J. and Antos, D. (2001) Inducible nitric oxide synthase and Salmonella infection. Microbes. Infect. 3, 771-776 https://doi.org/10.1016/S1286-4579(01)01428-9
  10. Nathan, C. and Shiloh, M. U. (2000) Reactive oxygen and nitrogen intermediates in the relationship between mammalian hosts and microbial pathogens. Proc. Natl. Acad. Sci. 97, 8841-8848
  11. Valle, E. and Guiney, D.G. (2005) Characterization of Salmonella-induced cell death in human macrophagelike THP-1 cells. Infect. Immun. 73, 2835-2840 https://doi.org/10.1128/IAI.73.5.2835-2840.2005
  12. Miriagou, V., Carattoli A. and Fanning S. (2006) Antimicrobial resistance islands: resistance gene clusters in Salmonella chromosome and plasmids. Microbes. Infect. 8(7), 1923-30 https://doi.org/10.1016/j.micinf.2005.12.027
  13. MacFarlane, A. S., Schwacha, M. G. and Eisenstein T. K. (1999) In vivo blockage of nitric oxide with aminoguanidine inhibits immunosuppression induced by an attenuated strain of Salmonella typhimurium, potentiates Salmonella infection, and inhibits macrophage and polymorphonuclear leukocyte influx into the spleen. Infect. Immun. 67, 891-898
  14. Umezawa, K., Akaike, T., Fujii, S., Suga, M., Setoguchi, K., Ozawa, A. and Maeda, H. (1997) Induction of nitric oxide synthesis and xanthine oxidase and their roles in the antimicrobial mechanism against Salmonella typhimurium infection in mice. Infect. Immun.,65, 2932-2940
  15. Kim, S., Watarai, M., Kondo Y., Erdenebaatar, J., Makino S. and Shirahata T. (2003) Isolation and characterization of mini-Tn5Km2 insertion mutants of Brucella abortus deficient in internalization and intracellular growth in HeLa cells. Infect. Immun. 3020-3027 https://doi.org/10.1128/IAI.71.6.3020-3027.2003
  16. Margaret, W., Nilofer, Q., Nancy, S. and Gary, S. (2001) High levels of nitric oxide production decrease early but increase late survival of Brucella abortus in macrophages. Microbial Pathogenesis 31,221-230 https://doi.org/10.1006/mpat.2001.0463
  17. Oumzil, H., Ghoulami, S., Rhajaoui, M., Ilidrissi, A., Fkih-Tetouani, S., Faid, M. and Benjouad A. (2002) Antibacterial and antifungal activity of essential oils of Mentha suaveolens. Phytother Res. 16, 727-731 https://doi.org/10.1002/ptr.1045
  18. Martins, A. P., Salgueiro, L. R., Goncalves, M. J., Vila, R., Tomi, F., Adzet, T. and Casanova J. (2000) Antimicrobial activity and chemical composition of the bark oil of Croton stellulifer, an endemic species from S. Tome e Príncipe. Planta Med. 66, 647-650 https://doi.org/10.1055/s-2000-8623
  19. Foster, J. W. and Spector M. P. (1995) How Salmonella survive against the odds. Annu. Rev. Microbiol. 49, 145-174 https://doi.org/10.1146/annurev.mi.49.100195.001045
  20. Lu, S., Manges, A. R., Xu, Y., Fang, F. C. and Riley L. W. (1999) Analysis of virulence of clinical isolates of Salmonella enteritidis in vivo and in vitro. Infect. Immun. 67, 5651-5657
  21. Kwon, K. B., Kim, E. K., Shin, B. C., Seo, E. A., Yang, J. Y. and Ryu, D. G., (2003) Herba houttuyniae extract induces apoptotic death of human promyelocytic leukemia cells via caspase activation accompanied by dissipation of mitochondrial membrane potential and cytochrome c release. Exp. Mol. Med. 35, 91-97 https://doi.org/10.1038/emm.2003.13
  22. Guiney, D. G. (2005) The role of host cell death in Salmonella infections. Curr. Top. Microbiol. Immunol. 2005; 289, 131-50 https://doi.org/10.1007/3-540-27320-4_6
  23. Chakravortty, D. and Hensel, M. (2003) Inducible nitric oxide synthase and control of intracellular bacterial pathogens. Microbes. Infect. 5, 621-627 https://doi.org/10.1016/S1286-4579(03)00096-0
  24. Macmicking, J. D., Xie, Q. W. and Nathan, C. (1997) Nitric oxide and macrophage function. Annu. Rev. Immunol. 15, 323-350 https://doi.org/10.1146/annurev.immunol.15.1.323
  25. Xie, Q. W., Cho, H. J., Calaycay, J., Mumgord , R. A., Swiderek, K. M., Lee, T. D., Ding, A., Troso, T. and Nathan, C. (1992) Cloning and characterization of inducible nitric oxide synthase from mouse macrophages. Science 256, 225-228 https://doi.org/10.1126/science.1373522
  26. Garci-a-del Portillo, F. (1996) Interaction of Salmonella with lysosomes of eukaryotic cells. Microbiologia. 12(2), 259-66

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