DOI QR코드

DOI QR Code

Evaluation of In Vivo Safety of Inhibitory Compounds from Cheongmoknosang Mulberry Leaves against Helicobacter pylori

청목노상 뽕잎으로부터 분리한 Helicobacter pylori 저해물질에 대한 In Vivo 안전성 평가

  • Kim, Byong-Oh (Dept. of Applied Biology, Kyungpook National University) ;
  • Cho, Young-Je (School of Food Science & Biotechnology, Food & Bio-Industry Research Institute, Kyungpook National University)
  • 김병오 (경북대학교 생물응용) ;
  • 조영제 (경북대학교 식품공학부, 식품생물산업연구소)
  • Received : 2011.07.29
  • Accepted : 2011.08.19
  • Published : 2011.10.31

Abstract

Biological compounds (caffeic acid, rosemarinic acid, and chlorogenic acid) from mulberry leaf extracts were administered to mice in order to confirm their stability. All male and female mice survived upon a 4,000 mg/g dose in an acute toxicity test, and they also survived after injection of 2,000 mg/kg for 13 weeks repeatedly. Therefore, the level of toxicity was not high. In a comparison of the control and test groups, there were no significant differences upon naked eye inspection, and the weights of stomachs infected by Helicobacter pylori were not significantly different. Regarding the effects on immune cells, NO of macrophages decreased more than that of control when medicine was administered. The spleens of the female mice group proliferated slightly in LPS and Con A within 48 hr, whereas the other test group showed a similar level and the cell toxicity of natural killing cells decreased. Therefore, we concluded that caffeic acid, rosemarinic acid, and chlorogenic acid from mulberry leaf extracts are not harmful for the treatment of infected patients the development as a healthy functional food.

뽕잎에서 분리한 유효성분의 혼합물에 대한 안전성을 확인하기 위하여 경구 투여하여 시험한 결과, 투여량 4000 mg/kg에서 암수 mouse 모두가 생존하여 급성독성은 없을 것으로 판단하였으며, 13주 반복 독성 시험에서도 투여량 2000 mg/kg에서 암수 mouse 모두가 생존하여 약물의 독성에 의한 문제는 없을 것으로 판단되었다. 육안으로는 대조군과 비교 시 이상이 확인되지 않았으며 부검 후 H. pylori 의 감염에 영향을 받을 수 있는 위의 무게 역시 대조군과의 차이를 확인할 수 없었다. 면역세포에 대한 영향은 약물 투여 시 매체대조군에 비해 대식세포의 독성 물질인 NO의 생성이 감소하는 것을 확인하였다. 또한 암컷군에서 48시간에서만이 LPS와 Con A에 의해 비장세포가 약간 증식되었을 뿐 다른 실험군에서는 대조구와 비슷한 수치를 나타내었으며, 자연살해세포의 세포독성은 감소되었다. 뽕잎에서 분리한 유용 성분인 caffeic acid, rosemarinic acid와 chlorogenic acid가 H. pylori의 감염환자의 치료용 또는 예방의 목적으로 임상적으로 사용할 경우 아무런 독성이 없을 것으로 판단되어 뽕잎을 건강기능성 식품으로 개발하는데 있어서 안전성 문제는 없는 것으로 판단되었다.

Keywords

References

  1. Fridovich I. 1989. Superoxide dismutase an adaption to paramagnetic gas. J Biol Chem 264: 7761-7762.
  2. Halliwell B, Aruoma OJ. 1991. DNA damage by oxygenderived species. FEBS Lett 281: 9-19. https://doi.org/10.1016/0014-5793(91)80347-6
  3. Higasi GS. 2000. Appraisement of antioxidative activity from vegetables. Jpn J Food Ind 57: 56-64.
  4. Hubue G, Wray V, Nahrstedt A. 1999. Flavonol oligosaccharides from the seeds of Aesculus hippocastanum. Planta Med 65: 636-642. https://doi.org/10.1055/s-1999-14038
  5. Iwuoha CI, Aina JO. 1997. Effects of steeping condition and germination time on the alpha-amylase activity, phenolics content and malting loss of Nigerian local red and hybrid short kaura sorghum malt. Food Chem 58: 289-295. https://doi.org/10.1016/0308-8146(95)00215-4
  6. Jennings PE, Barnett AH. 1998. New approaches to the pathogenesis and treatment of diabetic microangiopathy. Diabetic Med 5: 111-117.
  7. Jorge M, Ricardo DS, Jacques R, Vemonique C, Anni C, Michel M. 1991. Procyanidin dimers and trimers from grape seeds. Phytochemistry 30: 1259-1264. https://doi.org/10.1016/S0031-9422(00)95213-0
  8. Cho YJ, Chun SS, Lee KH, Kim JH, Kwon HJ, An BJ, Kim MU. 2006. Screening of the antimicrobial activity against Helicobacter pylori and antioxidant by extracts from mulberry fruits. J Korean Soc Food Sci Nutr 35: 15-20. https://doi.org/10.3746/jkfn.2006.35.1.015
  9. Cho YJ, Ju IS, Kim BO, Kim JH, Lee BG, An BJ, Choo JW. 2007. The antimicrobial activity against Helicobacter pylori and antioxidant effect from the extracts of mulberry leaves. J Kor Soc Appl Biol Chem 50: 334-343.
  10. Ju IS, Cho YJ. 2009. Purification and identification of phenol compounds with inhibitory activity on Helicobacter pylori from Rhododendron mucronulatum Flos. extracts. J Life Sci 19: 1125-1131. https://doi.org/10.5352/JLS.2009.19.8.1125
  11. Park KT, Kim JS, Jo BS, An BJ, Chun SS, Kim JH, Cho YJ. 2010. Isolation and identification of inhibitory compounds on Helicobacter pylori from Rosa multiflora Thunberg fruit extracts. J Life Sci 20: 1511-1518. https://doi.org/10.5352/JLS.2010.20.10.1511
  12. Cho YJ, Lee KH, Cha WS, Ju IS, Yun DH, An BJ, Lee SH, Kim MU, Chun SS. 2009. Purification and identification of inhibitory compounds from Cheongmoknosang mulberry leaves on Helicobacter pylori. J Appl Biol Chem 52: 65-69. https://doi.org/10.3839/jabc.2009.012
  13. Yun DH, Cha WS, Lee SH, An BJ, Kim JH, Chun SS, Bae JH, Cho YJ. 2010. Purification and identification of inhibitory compounds on Helicobacter pylori from Cheongmiknosang callus for biomass. J Life Sci 20: 374-380. https://doi.org/10.5352/JLS.2010.20.3.374
  14. McCartney-Francis N, Allen JB, Mizel DE, Albina JE, Xie QW, Nathan CF, Wahl SM. 1993. Suppression of arthritis by an inhibitor of nitric oxide synthase. J Exp Med 178: 749-754. https://doi.org/10.1084/jem.178.2.749
  15. Stuehr DJ. 1999. Mammalian nitric oxide synthase. Biochem Biophys Acta 1411: 217-230. https://doi.org/10.1016/S0005-2728(99)00016-X
  16. Weisz A, Cicatiello L, Esumi H. 1996. Regulation of the mouse inducible-type nitric oxide synthase gene promoter by interferon-gamma, bacterial lipopolysaccharide and NG-monomethyl-L-arginine. J Biochem 316: 209-215. https://doi.org/10.1042/bj3160209

Cited by

  1. Inhibitory Activity against Helicobacter pylori of Isolated Compounds from Pinus koraiensis Siebold et Zucc Leaves vol.59, pp.1, 2016, https://doi.org/10.3839/jabc.2016.005
  2. Fermentation Characteristics and anti-Helicobacter pylori Activity of Aqueous Broccoli Fermented by Lactobacillus plantarum MG208 vol.58, pp.1, 2015, https://doi.org/10.3839/jabc.2015.015