Advances in Traditional Medicine

Kyung Hee Oriental Medicine Research Center (경희대학교 융합한의과학연구소)
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Antioxidant activity and anti-tumor immunity by Propolis in mice

  • Choi, In-Sook (Graduate School of Health Science, Suzuka University of Medical Science) ;
  • Itokawa, Yuka (Graduate School of Health Science, Suzuka University of Medical Science) ;
  • Maenaka, Toshihiro (Graduate School of Health Science, Suzuka University of Medical Science) ;
  • Yamashita, Takenori (Graduate School of Health Science, Suzuka University of Medical Science) ;
  • Mitsumoto, Morihide (Graduate School of Health Science, Suzuka University of Medical Science) ;
  • Tano, Kaoru (Department of Acupuncture Moxibustion, Faculty of Acupuncture Moxibustion, Suzuka University of Medical Science) ;
  • Kondo, Hiroyo (Department of Clinical Nutrition, Faculty of Health Science, Suzuka University of Medical Science) ;
  • Ishida, Torao (Department of Acupuncture Moxibustion, Faculty of Acupuncture Moxibustion, Suzuka University of Medical Science,Hi-tech Research Center, Suzuka University of Medical Science) ;
  • Nakamura, Takashi (Graduate School of Health Science, Suzuka University of Medical Science) ;
  • Saito, Kiyoto (Graduate School of Health Science, Suzuka University of Medical Science) ;
  • Terai, Kaoru (Graduate School of Health Science, Suzuka University of Medical Science) ;
  • Monzen, Hajime (Graduate School of Health Science, Suzuka University of Medical Science) ;
  • Oshima, Masami (Graduate School of Health Science, Suzuka University of Medical Science) ;
  • Takeuchi, Tetsuo (Bio Queen Co., Ltd, Research Center) ;
  • Mituhana, Yuicti (Akeai clinic) ;
  • Bamen, Kenichi (Akeai clinic) ;
  • Ahn, Kyoo-Seok (Department of Pathology, College of Oriental medicine, Institute of Oriental Medicine, Kyunghee University) ;
  • Gu, Yeun-Hwa (Graduate School of Health Science, Suzuka University of Medical Science,Hi-tech Research Center, Suzuka University of Medical Science)
  • Published : 2005.06.30
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Abstract

In South America, natural products with unknown drug effects are used as folk remedies and for preventive medicine. Among South American natural products, we directed our attention to Propolis, which have been known as medicinal plants, and examined the mechanisms by which these substances affect antioxidant activity, anti-tumor activity and immunoresponse. When the antioxidant activities of Propolis were examined by the DPPH and Rhoudan iron methods, since Propolis contains high levels of flavonoids, it is thought that flavonoids may be responsible for the antioxidant activity in this study. In the examination of immunoenhancement activity, we measured lymphocyte versus polymorphonuclear leukocyte ratios (L/P activity). The number of lymphocytes was significantly increased in groups treated with Proplolis. Specifically, slightly high levels of $IFN-{\gamma}$ were measured in mice bearing the S-180 carcinoma, after administration of Propolis. This strongly suggests that cellular immunity is especially activated by treatment with Propolis, because production of $IFN-{\alpha}$ is limited to the T cells and NK cells stimulated by mitogen and sensitized antigen. $TNF-{\alpha}$ shows a different extent and mechanism of action depending on the target cells. When $TNF-{\alpha}$ was measured in mice bearing the S-180 carcinoma, mice treated with Propolis showed slightly higher $TNF-{\alpha}$ levels as compared to the control group. This suggests that activated macrophages produce $TNF-{\alpha}$ in mice treated with Prapolis, since activated macrophages and lymphocytes are the source of most $TNF-{\alpha}$. When anti-tumor action was examined using two kinds of sarcoma (Ehrlich solid carcinoma and Sarcoma-180 carcinoma), tumor-suppressive ratios after treatment with Propolis was 29.1%. When Sarcoma-180 solid carcinoma was used, tumor-suppressive ratios were 62%. Thus, Propolis showed strong anti-tumor activity against two kinds of solid carcinoma. Taken altogether, this strongly suggests that Propolis enhances original functions of macrophages and NK cells, and as a result, secondarily enhances the immune reaction and suppresses tumor growth.

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References

  1. Anderson CF, Mendez S, Sacks DL. (2005) Nonhealing infection despite Th1 polarization produced by a strain of leishmania major in C57BL/6 Mice. J. Immunol. 174, 2934-2941.
  2. Aso K, Kanno S, Tadano T, Satoh S, Ishikawa M. (2004) Inhibitory effect of propolis on the growth of human leukemia U937. Biol. Pharm. Bull. 27, 727-730. https://doi.org/10.1248/bpb.27.727
  3. Chang SC, Rodrigues NP, Zurgil N, Henderson JR, Bedioui F, McNeil CJ, Deutch M. (2005) Simultaneous intra- and extracellular superoxide monitoring using an integrated optical and electrochemical sensor system. Biochem. Bioph. Res. Co. 327, 979-984. https://doi.org/10.1016/j.bbrc.2004.12.108
  4. Chen YT, Zheng RL, Jia Z, Ju Y. (1990) Flavonoids as superoxide scavengers and antioxidants free radical. Biol. Med. 9, 19-21.
  5. Chen XC, Zhou YC, Chen Y, Zhu YG, Fang F, Chen LM. (2005) Ginsenoside Rg1 reduces MPTP-induced substantia nigra neuron loss by suppressing oxidative stress. Acta Pharmacol. Sin. 26, 56-62. https://doi.org/10.1111/j.1745-7254.2005.00019.x
  6. Del BP, Rotilio D. (2004) Quantitative analysis of caffeic acid phenethyl ester in crude propolis by liquid chromatography-electrospray ionization mass spectrometry. J. Sep. Sci. 27, 619-623. https://doi.org/10.1002/jssc.200301628
  7. Duhen T, Pasero C, Mallet F, Barbarat B, Olive D, Costello RT. (2004) LIGHT costimulates CD40 triggering and induces immunoglobulin secretion; a novel key partner in T cell-dependent B cell terminal differentiation. Eur. J. Immunol. 34, 3534-3541. https://doi.org/10.1002/eji.200425598
  8. Flescher E, Ledbetter JA, Schieven GL, Vela-Roch N, Fossum D, Dang H, Ogawa N, Talal N. (1994) Longitudinal exposure of human T lymphocytes to weak oxidative stress suppresses transmembrane and nuclear signal transduction. J. Immunol. 153, 4880-4889.
  9. Gach JE, Humphreys F, Berth-Jones J. (2005) Randomized, double-blind, placebo-controlled pilot study to assess the value of free radical scavengers in reducing inflammation induced by cryotherapy. Clin. Exp. Dermatol. 30, 14-16. https://doi.org/10.1111/j.1365-2230.2004.01694.x
  10. Glinsky GV, Price JE, Glinsky VV, Mossine VV, Kiriakova G, Metcalf JB. (1996) Inhibition of human breast cancer metastasis in nude mice by synthetic glycoamines. Cancer Res. 56, 5319-5324.
  11. Hirose L, Nosaka K, Newton M, Laveder A, Kano M, Peake J, Suzuki K. (2004) Changes in inflammatory mediators following eccentric exercise of the elbow flexors. Exerc. Immunol. Rev. 10, 75-90.
  12. Ikukatsu S, Yasuyuki T, Ikuo H. (2002) Antitumor and anticytopenic effects of aqueous extracts of propolis in combination with chemotherapeutic agents. Cancer Biother. Radio. 17, 553-562. https://doi.org/10.1089/108497802760804781
  13. Kalinski P, Giermasz A, Nakamura Y, Basse P, Storkus WJ, Kirkwood JM, Mailliard RB. (2005) Helper role of NK cells during the induction of anticancer responses by dendritic cells. Mol. Immunol. 42, 535-539. https://doi.org/10.1016/j.molimm.2004.07.038
  14. Kuo KL, Weng MS, Oliang CT, Tsai YJ, Lin-Shiau SY, Lin JK. (2005) Comparative studies on the hypolipidemic and growth suppressive effects of Oolong, Black, Pu-erh, and Green Tea Leaves in rats. J. Agr. Food Chem. 53, 480-489. https://doi.org/10.1021/jf049375k
  15. Leitao DP, Filho AA, Polizello AC, Bastos JK, Spadaro AC. (2004) Comparative evaluation of in-vitro effects of Brazilian green propolis and Baccharis dracunculifolia extracts on cariogenic factors of Streptococcus mutans. Biol. Pharm. Bull. 27, 1834-1839. https://doi.org/10.1248/bpb.27.1834
  16. Lin MW, Yang SR, Huang MH, Wu SN. (2004) Stimulatory actions of caffeic acid phenethyl ester, a known inhibitor of NF-kappaB activation, on $Ca^{2+}$-activated $K^+$ current in pituitary GH3 cells. J. Biol. Chem. 279, 26885-26892. https://doi.org/10.1074/jbc.M400356200
  17. Liou CJ, Li ML, Tseng J. (2004) Intraperitoneal injection of ginseng extract enhances both immunoglobulin and cytokine production in mice. Am. J. Chin. Med. 32, 75-88. https://doi.org/10.1142/S0192415X04001771
  18. Majiene D, Trumbeckaite S, Grunoviene D, Ivanauskas L, Gendrolis A. (2004) Investigation of chemical composition of propolis extract. Medicina (Kaunas) 40, 771-774.
  19. Matsui T, Ebuchi S, Fujise T, Matsugano K, Terahara N, Matsumoto K. (2004) Strong antihyperglycemic effects of water-soluble fraction of Brazilian propolis and its bioactive constituent, 3,4,5-tri-O-caffeoylquinic acid. Biol. Pharm. Bull. 27, 1797-1803. https://doi.org/10.1248/bpb.27.1797
  20. Mizutani A, Yamamoto H, Suzuki I. (1978) Antitumor activity of bovine parotid hypocalcemic substance obtained by glacial acetic acid extraction. Gann. 69, 291-297.
  21. Murata K, Yatsunami K, Fukuda E, Onodera S, Mizukami O, Hoshino G, Kamei T. (2004) Antihyperglycemic effects of propolis mixed with mulberry leaf extract on patients with type 2 diabetes. Altern. Ther. Health M. 10, 78-79.
  22. Orsolic N, Sver L, Terzic S, Tadic Z, Basic I. (2003) Inhibitory effect of water-soluble derivative of propolis and its polyphenolic compounds on tumor growth and metastasizing ability: a possible mode of antitumor action. Nutr. Cancer 47, 156-163. https://doi.org/10.1207/s15327914nc4702_8
  23. Sapi E, Alvero AB, Chen W, O'Malley D, Hao XY, Dwipoyono B, Garg M, Kamsteef M, Rutherford T, Mor G. (2004) Resistance of ovarian carcinoma cells to docetaxel is XIAP dependent and reversible by phenoxodiol. Oneal. Res. 14, 567-578.
  24. Scheller S. (1989) The ability of ethanolic extract of propolis (EEP) to protect mice against gamma irradiation. Z. Naturforsch. C 44, 1049-1052.
  25. Usami E, Kusano G, Katayose T. Wachi H, Seyama Y. (2004) Assessment of antioxidant activity of natural compound by water- and lipid-soluble antioxidant factor. Yakugaku Zasshi 124, 847-850. https://doi.org/10.1248/yakushi.124.847
  26. Volpi N. (2004) Separation of flavonoids and phenolic acids from propolis by capillary zone electrophoresis. Electrophoresis 25, 1872-1878. https://doi.org/10.1002/elps.200405949
  27. Yong KP. (1998) Preparation of water and ethanolic extracts of propolis and evaluation of the preparations. Biosci. Biotech. Bioch. 62, 2230-2232. https://doi.org/10.1271/bbb.62.2230
  28. Zuo XJ, Nicolaidou E, Okada Y, Toyoda M, Jordan SC. (2001) Antithrombin III inhibits lymphocyte proliferation, immunoglobulin production and mRNA expression of lymphocyte growth factors (IL-2, gamma-IFN and IL-4) in vitro. Transpl. Immunol. 9, 1-6. https://doi.org/10.1016/S0966-3274(01)00042-9