Korean Journal of Food Science and Technology (한국식품과학회지)

Korean Society of Food Science and Technology (한국식품과학회)
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Immunomodulatory Effects of Propolis and Fermented-propolis in BALB/c Mice

프로폴리스 및 발효 프로폴리스의 섭취가 BALB/c mice의 면역활성에 미치는 영향

  • Kim, Yoon-Hee (Center for Efficacy Assessment and Development of Functional Foods and Drugs, Hallym University) ;
  • Kwon, Hyuck-Se (Center for Efficacy Assessment and Development of Functional Foods and Drugs, Hallym University) ;
  • Kim, Dae-Hwan (Center for Efficacy Assessment and Development of Functional Foods and Drugs, Hallym University) ;
  • Park, IL-Hwan (Korea Agricultural Propolis Inc.) ;
  • Park, Sang-Jae (Korea Agricultural Propolis Inc.) ;
  • Shin, Hyun-Kyung (Department of Food Science and Nutrition, Hallym University) ;
  • Kim, Jin-Kyung (Center for Efficacy Assessment and Development of Functional Foods and Drugs, Hallym University)
  • 김윤희 (한림대학교 식의약품의 효능평가 및 기능성 소재 개발센터) ;
  • 권혁세 (한림대학교 식의약품의 효능평가 및 기능성 소재 개발센터) ;
  • 김대환 (한림대학교 식의약품의 효능평가 및 기능성 소재 개발센터) ;
  • 박일환 (한국양봉프로폴리스) ;
  • 박상재 (한국양봉프로폴리스) ;
  • 신현경 (한림대학교 식품영양학과) ;
  • 김진경 (한림대학교 식의약품의 효능평가 및 기능성 소재 개발센터)
  • Published : 2008.10.31
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Abstract

Propolis is the generic term for the resinous substance collected by honey bees from a variety of plant sources. In this study, we have assessed the immunomodulatory properties of propolis (P) and fermented-propolis (FP) in BALB/c mice. Mice were subjected to gavage once a day (for 14 days) with 50, 100, 200 mg/kg body weight P, FP, or vehicle. Lymphocytes were isolated from the spleen and mesenteric lymph nodes (MLN) and the immune cell proportions, proliferative activities, and cytokine production were evaluated. The P- and FP-administration induced similar, but differential, alterations in the percentage of immune cell populations and their biological functions, including cytokine production and NK cell cytotoxicity. The proportion of$ CD4^+$ and $CD8^+$ T cells in the spleen was increased slightly in the P- and FP-administered mice as compared to the vehicle-treated mice. In MLN, the percentage of $CD4^+$ T cells was increased significantly in the 200 mg/kg P-treated mice. The mice which were treated with P and FP evidenced significantly increased interferon-$\gamma$ and interleukin-4 production in concanavalin A-stimulated splenocytes, whereas the production of theses cytokines was not shown to be induced by P-treatment. In addition, NK cell activity was also increased dramatically by the administration of P and FP. Collectively, these findings showed that P and FP are wide-spectrum immunomodulators, which may modulate both innate and adaptive immune responses.

본 연구는 프로폴리스 추출물 및 발효 프로폴리스 추출물의 투여에 의한 면역활성에 미치는 영향을 검토하기 위하여 수행하였다. 프로폴리스 추출물 및 발효 프로폴리스 추출물을 체중 kg 당 50, 100, 200 mg/kg의 농도로 BALB/c 마우스에게 14일 동안 연속적으로 경구투여한 후, 이러한 시험물질 투여에 기인한 비장림프구와 창자간막 림프구의 증식능, 림프구의 아집단 비율의 변화 및 사이토카인 분비능을 측정하였다. 또한 비장 림프구로부터 NK 세포를 분리하여 YAC-1 세포를 살해하는 NK 세포의 활성을 측정하였다. 그 결과 프로폴리스 및 발효 프로폴리스의 투여에 의해 비장 림프구와 창자간막 림프구의 T 림프구($CD3^+$) 비율이 증가하는 경향을 보였으며, 이는 $CD4^+$와 $CD8^+$ T 림프구 비율의 증가에 기인하였다. 비장 및 창자간막 림프절로부터 분리한 림프구의 증식능도 프로폴리스 및 발효 프로폴리스 투여에 의해 증가되는 것을 관찰할 수 있었다. Th-1/Th-2 사인토카인 분비에 미치는 영향을 관찰한 결과 비장림프구에서는 발효 프로폴리스 추출물이 프로폴리스 추출물에 비하여 IFN-$\gamma$, IL-2, IL-4의 분비를 증강시키는 것을 확인할 수 있었다. 창자간막 림프구의 Th-2 사이토카인 분비증강은 고농도(200 mg/kg)의 프로폴리스 및 발효 프로폴리스 추출물 투여군에서만 관찰되었다. 프로폴리스 및 발효 프로폴리스 투여에 의해 YAC-1 세포를 살해하는 NK 세포의 활성도 유의적으로 증가하였다. 이상의 결과로, 프로폴리스 및 발효 프로폴리스 추출물의 경구투여는 체내 면역기능을 증강 시킬 수 있는 면역조절제로서의 가능성을 가지는 것으로 사료된다.

Keywords

References

  1. Salem ML. Immunomodulatory and therapeutic properties of the Nigella sativa L. Seed. Int. Immunopharmacol. 5: 1749-1770 (2005) https://doi.org/10.1016/j.intimp.2005.06.008
  2. Ryu HS, Kim J, Kim HS. Enhancing effect of Sorghum bicolor L. Moench (Sorghum, su-su) extracts on mouse spleen and macrophage cell activation. J. Korean Food Nutr. 19: 176-182 (2006)
  3. Agarwal BB, Traquna PR, Eessalu TE. Modulation of receptor and cytotoxic response of tumor necrosis factor-L by various lectins. J. Biol. Chem. 261: 13652-13656 (1986)
  4. Belardelli F, Ferrantimi M. Cytokines as a link between innate and adaptive antitumor immunity. Trends Immunol. 23: 201-208 (2002) https://doi.org/10.1016/S1471-4906(02)02195-6
  5. Diefenbach A, Rauler DH. The innate immune response to tumors and its role in the induction of T-cell immunity. Immunol. Rev. 188: 9-21 (2002) https://doi.org/10.1034/j.1600-065X.2002.18802.x
  6. Kumazawa SH, Yoneda M, Shibata I, Kanaeda J, Hamasaka T, Nakayama TS. Direct evidence for the plant origin of Brazilian propolis by the observation of honeybee behavior and phytochemical analysis. Chem. Pharm. Bull. 51: 740-742 (2003) https://doi.org/10.1248/cpb.51.740
  7. Bankova V. Recent trends and important developments in propolis research. Evid. Based Complement. Alternat. Med. 2: 29-32 (2005) https://doi.org/10.1093/ecam/neh059
  8. Bazo AP, Rodrigues MAM, Sforcin JM, de Camargo JLV, Ribeiro LR, Salvadori DMF. Protective action of propolis on the rat colon carcinogenesis. Teratogen. Carcin. Mut. 22: 183-194 (2002) https://doi.org/10.1002/tcm.10011
  9. El-khawaga O-AY, Salem TA, Elshal MF. Protective role of Egyptian propolis against tumor in mice. Clin. Chim. Acta 338: 11-16 (2003) https://doi.org/10.1016/S0009-8981(03)00323-1
  10. Orsolic N, Kosalec I, Ivan B. Synergistic antitumor effect of polyphenolic components of water soluble derivative of propolis against ehrlich ascites tumour. Biol. Pharm. Bull. 28: 694-700 (2005) https://doi.org/10.1248/bpb.28.694
  11. Ivanovska N, Neychev H, Stefanova Z, Bankova V, Popov S. Influence of cinnamic acid on lymphocyte proliferation, cytokine release, and Klebsiella infection in mice. Apidologie 26: 73-81 (1995) https://doi.org/10.1051/apido:19950201
  12. Sforcin, JM, Fernandes JA, Lopes CAM, Bankova V, Funari SR. Seasonal effect on Brazilian propolis antibacterial activity. J. Ethnopharmacol. 73: 243-249 (2000) https://doi.org/10.1016/S0378-8741(00)00320-2
  13. Vynograd N, Vynograd I, Sosnowski Z. A comparative multi-centre study of the efficacy of propolis, acyclovir and placebo in the treatment of genital herpes (HSV). Phytomedicine 7: 1-6 (2000) https://doi.org/10.1016/S0944-7113(00)80014-8
  14. Khayyal MT, El-Ghazaly MA, El-Khatib AS. Mechanisms involved in the anti-inflammatory effect of propolis extract. Drug Exp. Clin. Res. 19: 197-203 (1993)
  15. Ledon N, Casaco A, Gonzalez R, Merino N, Gonzalez A, Tolon Z. Antipsoriatic, anti-inflammatory, and analgesic effects of an extract of red propolis. Acta Pharmacol. Sin. 18: 274-276 (1997)
  16. Jeong IY. Antioxidant activity and radioprotection of two flavonoids from propolis. J. Korean Soc. Food Sci. Nutr. 34: 162- 166 (2005) https://doi.org/10.3746/jkfn.2005.34.2.162
  17. Park JH, Lee JK, Kim HS, Chung ST, Eom JH, Kim KA, Chung SJ, Paik SY, Oh HY. Immunomodulatory effect of caffeic acid phenethyl ester in BALB/c mice. Int. Immunopharmacol. 4: 429- 436 (2004) https://doi.org/10.1016/j.intimp.2004.01.013
  18. Andreia PD, Bianca PO, Fatima HMG, Solange L, De Castro. Treatment of Trypanosoma cruzi-infected mice with propolis promotes changes in the immune response. J. Ethnopharmacol. 103: 187-193 (2006) https://doi.org/10.1016/j.jep.2005.07.018
  19. Combe CL, Curiel TJ, Moretto MM, Khan IA. NK cells help to induce $CD8^+$ T cell immunity against Toxoplasma gondii in the absence of $CD4^+$ T cells. Infect. Immun. 73: 4913-4921 (2005) https://doi.org/10.1128/IAI.73.8.4913-4921.2005
  20. Takagi Y, Choi IS, Yamashita T, Nakamura T, Suzuki I, Hasegawa T, Oshima M, Gu YH. Immune activation and radioprotection by propolis. Am. J. Chin. Med. 33: 231-240 (2005) https://doi.org/10.1142/S0192415X05002886
  21. Sa-Nunes A, Faccioli LH, Sforcin JM. Propolis: Lymphocyte proliferation and IFN-gamma production. J. Ethnopharmacol. 87: 93- 97 (2003) https://doi.org/10.1016/S0378-8741(03)00121-1
  22. Wu D, Pae M, Ren Z, Guo Z, Smith D, Meydani SN. Dietary supplementation with white button mushroom enhances natural killer cell activity in C57BL/6 mice. J. Nutr. 137: 1472-1477 (2007)
  23. Song JJ, Gu Cho J, Hwang SJ, Gun Cho C, Park SW, Chae SW. Inhibitory effect of caffeic acid phenethyl ester (CAPE) on LPSinduced inflammation of human middle ear epithelial cells. Acta Otolaryngol. 8: 1-5 (2008) https://doi.org/10.3109/00016482509118208
  24. Jung WK, Lee DY, Choi YH, Yea SS, Choi I, Park SG, Seo SK, Lee SW, Lee CM, Kim SK, Jeon YJ, Choi IW. Caffeic acid phenethyl ester attenuates allergic airway inflammation and hyperresponsiveness in murine model of ovalbumin-induced asthma. Life Sci. 82: 797-805 (2008) https://doi.org/10.1016/j.lfs.2008.01.014
  25. Ribeiro U Jr, Safatle-Ribeiro AV. Caffeic acid phenethyl ester (CAPE) may be a promising adjuvant treatment in gastric cancer. J. Clin. Gastroenterol. 41:871-873 (2007) https://doi.org/10.1097/MCG.0b013e31806b5938
  26. Hsu LY, Lin CF, Hsu WC, Hsu WL, Chang TC. Evaluation of polyphenolic acid esters as potential antioxidants. Biol. Pharm. Bull. 28: 1211-1215 (2005) https://doi.org/10.1248/bpb.28.1211