The Journal of Korean Medicine (대한한의학회지)

The Society of Korean Medicine (대한한의학회)
권호 표지

Mixture of Wild Panax Ginseng and Red-Mold Rice Extracts Activates Macrophages through Protection of Cell Regression and Cytokine Expression in Methotrexate-Treated RAW264.7 Cells

  • Published : 2009.11.30
Download PDF
⟨ Previous Next ⟩

Abstract

Objective: In this study, the immunomodulatory activity of a mixture of wild Panax ginseng and red-mold rice extracts (MPR) on RAW 264.7 macrophage cells in the presence and absence of methotrexate (MTX), an anti-cancer drug, was investigated. Methods and Results: In the cell viability, MPR showed a significant cell proliferation and inhibited cell regression by red-mold rice (RMR) alone or MTX alone. MPR induced moderate increase in nitric oxide (NO) production. NO production and inducible nitric oxide synthase (iNOS) mRNA expression by LPS decreased after MPR treatment. In addition, MPR slightly induced COX-2 mRNA expression, but it did not affect the expression of COX-2 mRNA by LPS treatment. In RT-PCR analyses, MPR induced IL-$1{\alpha}$, IL-$1{\beta}$, IL-6, and TNF-$\alpha$ mRNA expression, but had no effect on IL-10 and TGF-$\beta$, regardless of MTX treatment. Furthermore, MPR did not interfere with the cytotoxicity of MTX against MCF-7 human breast carcinoma cells. Conclusions: MPR is efficacious in protecting against MTX-induced cell regression as a result of macrophage activation, resulting in induction of cytokine expression, implying that MPR could be considered an adjuvant in MTX-chemotherapy.

Keywords

References

  1. Gorlick R, Goker E, Trippett T, Waltham M, Banerjee B, Bertino JR. Intrinsic and acquired resistance to methotrexate in acute leukaemia. N Engl J Med. 1996; 335:1041-48. https://doi.org/10.1056/NEJM199610033351408
  2. Kremer MJ. 2004. Toward a better understanding of methotrexate. Arthritis Rheum. 2004; 50:1370-82. https://doi.org/10.1002/art.20278
  3. Mizuno M, Yamada J, Terai H, Kozukue N, Lee YS, Tsuchida H. Differences in immunomodulating effects between wild and cultured Panax ginseng. Biochem Biophys Res Commun. 1994; 200:1672-8. https://doi.org/10.1006/bbrc.1994.1644
  4. Gum SI, Jo SJ, Ahn SH, Kim SG, Kim JT, Shin HM, et al. The potent protective effect of wild ginseng (Panax ginseng C.A. Meyer) against benzo[$\alpha$]pyrene-induced toxicity through metabolic regulation of CYP1A1 and GSTs. J Ethnopharmacol. 2007; 112:568-76. https://doi.org/10.1016/j.jep.2007.05.014
  5. Tsuji K, Ichikawa T, Tanabe N, Obata H, Abe S, Tarui S, et al. Extraction of hypotensive substance from wheat beni-koji. Nippon: Shokuhin Kogyo Gakkaish. 1992a; 39:913-8. https://doi.org/10.3136/nskkk1962.39.913
  6. Tsuji T, Ichikawa T, Tanabe N, Abe S, Tarui S, Nakagawa Y. Effects of two kinds of Koji on blood pressure in spontaneously hypertensive rats. Nippon: Nogeikagaku Kaishi.1992b; 66:1241-6. https://doi.org/10.1271/nogeikagaku1924.66.1241
  7. Wong HC, Bau YS. Pigmentation and antibacterial activity of fast neutron-and X-ray induced strains of Monascus purpureus went. Plant Physiol. 1977; 60:578-81. https://doi.org/10.1104/pp.60.4.578
  8. Yu KW, Kim YS, Shin KS, Kim JM, Suh HJ. Macrophage-stimulating activity of exo-biopolymer from cultured rice bran with Monascus pilosus. Appl Biochem Biotechnol. 2005; 126:35-48. https://doi.org/10.1007/s12010-005-0004-6
  9. Jun SY, Choi YH, Shin HM. Siegesbeckia glabrescens induces apoptosis with different pathways in human MCF-7 and MDA-MB-231 breast carcinoma cells. Oncol Rep. 2006; 15:1461-67.
  10. Sun CC, Bodurka DC, Donato ML, Rubenstein EB, Borden CL, Basen-Engquist K, et al. Patient preferences regarding side effects of chemotherapy for ovarian cancer: Do they change over time? Gynecol Oncol. 2002; 87:118-28. https://doi.org/10.1006/gyno.2002.6807
  11. Auletta JJ, O'Riordan MA, Nieder ML. Infections in children with cancer: A continued need for the comprehensive physical examination. J Pediatr Hematol Oncol. 1999; 21:501-8. https://doi.org/10.1097/00043426-199911000-00011
  12. Furusawa E, Furusawa S. Anticancer potential of Viva-Natural, a dietary seaweed extract, on Lewis lung carcinoma in comparison with chemical immunomodulators and on cyclosporine-accelerated AKR leukemia. Oncology. 1989; 46:343-48. https://doi.org/10.1159/000226746
  13. Wong CK, Bao YX, Wong EL, Leung PC, Fung KP, Lam CW. Immunomodulatory activities of Yunzhi and Danshen in post-treatment breast cancer patients. Am J Chin Med. 2005; 33:381-95. https://doi.org/10.1142/S0192415X05002990
  14. Maisuo R, Ball MA, Kobayashi M, Herndon DN, Pollard RB, Suzuki F. Effects of a traditional Chinese herbal medicine, Kanzo-bushi-to, on the resistance of thermally injured mice infected with herpes simplex virus type 1. Int J Immunopharmacol. 1994; 16:855-63. https://doi.org/10.1016/0192-0561(94)90059-0
  15. Akagawa G, Abe S, Tansho S, Uchida K, Yamaguch, H. Protection of C3H/HE J mice from development of Candida albicans infection by oral administration of Juzen-taiho-to and its component, Ginseng radix: possible roles of macrophages in the host defense mechanisms. Immunopharmacol Immunotoxicol. 1996; 18:73-89. https://doi.org/10.3109/08923979609007111
  16. Kim JY, Germolec DR, Luster MI. Panax ginseng as a potential immunomodulator: studies in mice. Immunopharmacol Immunotoxicol. 1990; 12:257-76. https://doi.org/10.3109/08923979009019672
  17. Betz JM, DerMarderosian AH, Lee T. Continuing studies on the ginsenoside content of commercial ginseng products by TLC, and HPLC II. In: Proctor. J.T.A. (Ed), Proceedings of the 6th Annual North American ginseng conference. University of Guelph. Guelph, Canada. 1984; 65-83.
  18. Wang TH, Lin TF. Monascus rice products. Adv Food Nutr Res. 2007; 53:123-59. https://doi.org/10.1016/S1043-4526(07)53004-4
  19. Akihisa T, Touda H, Yasuawa K, Ukiya M, Kiyota A, Sakamoto N, et al. Azaphilones, Furanoisophthalides, and Amino Acids from the extracts of Monascus pilosus-fermented rice (red-mold rice) and their chemopreventive effects. J Agric Food Chem. 2005; 53:562-5. https://doi.org/10.1021/jf040199p
  20. Huennekens FM. The methotrexate story: a paradigm for development of cancer chemotherapeutic agents. Adv Enzyme Regul. 1994; 34:397-419. https://doi.org/10.1016/0065-2571(94)90025-6
  21. Hu SK, Mitcho YL, Oronsky AL, Kerwar SS. Studies on the effect of methotrexate on macrophage function. J Rheumatol. 1988; 15:206-9.
  22. Conolly KM, Stecher VJ, Danis E, Pruden DJ, LaBrie T. Alteration of interleukin-1 production and the acute phase response following medication of adjuvant arthritic rats with cyclosporin-A or methtrexate. Int J Immunopharmacol. 1988; 10:717-28. https://doi.org/10.1016/0192-0561(88)90025-2
  23. Genestier L, Paillot R, Fournerl S, Ferraro C, Miossec P, Revillard JP. Immunosuppression properties of methotrexate: apoptosis and clonal deletion of activated peripheral T cells. J Clin Invest. 1988; 102:322-28.
  24. Elisenstein TK, Dalal N, Killar L, Lee JC, Schater R. Paradoxes of immunity and immunosuppression in Salmonella infection. Adv. Exp. Med. Biol. 1988; 239:353-66.
  25. Hibbs JB, Taintor RR, Vavrin Z. Macrophage cytotoxicity: Role for L-arginine dieminase and imino nitrogen oxidation to nitrite. Science. 1987; 235:473-76. https://doi.org/10.1126/science.2432665
  26. Green SJ, Meltzer MS, Hibbs JB, Nacy CA. Activated macrophages destroy intracellular Leishmania major amastigotes by an L-arginine-dependent killing mechanism. J Immunol. 1990; 144:278-83.
  27. Riese J, Hoff T, Nordhoff A, DeWitt DL, Resch K, Kaever V. Transient expression of prostaglandin endoperoxide synthase-2 during mouse macrophage activation. J Leukoc Biol. 1994; 55:476-82. https://doi.org/10.1002/jlb.55.4.476
  28. Phillips TA, Kujubu DA, MaeKay RJ, Herschman HR, Russel SW, Pace JL. The mouse macrophage activation-associated marker protein, p71/73, is an inducible prostaglandin endoperoxide synthase (cyclooxygenase-1). J Leukoc Biol. 1993; 53:411-9. https://doi.org/10.1002/jlb.53.4.411
  29. Mauel J, Ransijn A, Corradin SB, Buchmuller-Rouiller Y. Effect of $PGE_{2}$ and of agents that raise camp levels on macrophage activation induced by $IFN-\gamma$ and $TNF-\alpha$. J Leukoc Biol. 1995; 58:217-24. https://doi.org/10.1002/jlb.58.2.217
  30. Panaro MA, Brandonisio O, Sisto M, Acquafredda A, Leogrande D, Fumarola L, et al. Nitric oxide production by Leishmania-infected macrophages and modulation by prostaglandin E2. Clin Exp Med. 2001; 1:137-43. https://doi.org/10.1007/s10238-001-8025-0
  31. Choy YM, Leung KN, Cho CS, Wong CK, Pang PK. Immuno-pharmacological studies of low molecular weight polysaccharide from Angelica sinesis. Am J Chin Med. 1994; 22:137-45. https://doi.org/10.1142/S0192415X94000176
  32. Lee YS, Chung IS, Lee IR, Kim KH, Hong WS, Yun YS. Activation of multiple effector pathways of immune system by the antineoplastic immunostimulator acidic polysaccharide ginsan isolated from Panax ginseng. Anticancer Res. 1997; 17:323-31.
  33. Lee YG, Kim JY, Lee JY, Byeon SE, Hong EK, Lee J, et al. Regulatory effects of Codonopsis lancealata on macrophage-mediated immune responses. J Ethnopharmacol. 2007; 112:180-8. https://doi.org/10.1016/j.jep.2007.02.026
  34. Yesilada E, Bedir E, Calis I, Takaishi Y, Ohmoto Y. Effects of triterpene saponins from Astragalus species on in vitro cytokine release. J Ethnopharmacol. 2005; 96:71-7. https://doi.org/10.1016/j.jep.2004.08.036
  35. Lee YS, Han OK, Park CW, Suh SI, Shin SW, Yang CH, et al. Immunomodulatory effects of aqueous-extracted Astragali radix in methotrexate-treated mouse spleen cells. J Ethnopharmacol. 2003; 84:193-8. https://doi.org/10.1016/S0378-8741(02)00298-2
  36. Park JS, Lee JH, Ha TY. Effects of capsaicin pretreatment on the function of mouse peritoneal macrophages. Korean J Immunol. 2000; 22:39-49.