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

다국어 초록 (Multilingual 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-1α, IL-1β, IL-6, and TNF-α mRNA expression, but had no effect on IL-10 and TGF-β, 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.

참고문헌 (Reference)

1 Gum SI, "potent protective effect of wild ginseng (Panax ginseng C.A. Meyer) against benzo[α]pyrene-induced toxicity through metabolic regulation of CYP1A1 and GSTs" 112 : 568-576, 2007

2 Riese J, "Transient expression of prostaglandin endoperoxide synthase-2 during mouse macrophage activation" 55 : 476-482, 1994

3 Kremer MJ, "Toward a better understanding of methotrexate" 50 : 1370-1382, 2004

4 Phillips TA, "The mouse macrophage activation-associated marker protein, p71/73, is an inducible prostaglandin endoperoxide synthase (cyclooxygenase-1)" 53 : 411-419, 1993

5 20. Huennekens FM, "The methotrexate story: a paradigm for development of cancer chemotherapeutic agents" 34 : 397-419, 1994

6 Hu SK, "Studies on the effect of methotrexate on macrophage function" 15 : 206-209, 1988

7 Jun SY, "Siegesbeckia glabrescens induces apoptosis with different pathways in human MCF-7 and MDA-MB-231 breast carcinoma cells" 15 : 1461-1467, 2006

8 Lee YG, "Regulatory effects of Codonopsis lancealata on macrophage-mediated immune responses" 112 : 180-188, 2007

9 Akagawa G, "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" 18 : 73-89, 1996

10 Wong HC, "Pigmentation and antibacterial activity of fast neutron-and X-ray induced strains of Monascus purpureus went" 60 : 578-581, 1977

11 Sun CC, "Patient preferences regarding side effects of chemotherapy for ovarian cancer: Do they change over time?" 87 : 118-128, 2002

12 Elisenstein TK, "Paradoxes of immunity and immunosuppression in Salmonella infection" 239 : 353-366, 1988

13 Kim JY, "Panax ginseng as a potential immunomodulator: studies in mice" 12 : 257-276, 1990

14 Panaro MA, "Nitric oxide production by Leishmania-infected macrophages and modulation by prostaglandin E2" 1 : 137-143, 2001

15 Wang TH, "Monascus rice products" 53 : 123-159, 2007

16 Yu KW, "Macrophage-stimulating activity of exo-biopolymer from cultured rice bran with Monascus pilosus" 126 : 35-48, 2005

17 Hibbs JB, "Macrophage cytotoxicity: Role for L-arginine dieminase and imino nitrogen oxidation to nitrite" 235 : 473-476, 235

18 Gorlick R, "Intrinsic and acquired resistance to methotrexate in acute leukaemia" 335 : 1041-1048, 1996

19 Auletta JJ, "Infections in children with cancer: A continued need for the comprehensive physical examination" 21 : 501-508, 1999

20 Genestier L, "Immunosuppression properties of methotrexate: apoptosis and clonal deletion of activated peripheral T cells" 102 : 322-328, 1988

21 Lee YS, "Immunomodulatory effects of aqueous-extracted Astragali radix in methotrexatetreated mouse spleen cells" 84 : 193-198, 2003

22 Wong CK, "Immunomodulatory activities of Yunzhi and Danshen in post-treatment breast cancer patients" 33 : 381-395, 2005

23 Choy YM, "Immuno-pharmacological studies of low molecular weight polysaccharide from Angelica sinesis" 22 : 137-145, 1994

24 Tsuji K, "Extraction of hypotensive substance from wheat beni-koji" 39 : 913-918, 1992a

25 Tsuji T, "Effects of two kinds of Koji on blood pressure in spontaneously hypertensive rats" 66 : 1241-1246, 1992b

26 Yesilada E, "Effects of triterpene saponins from Astragalus species on in vitro cytokine release" 96 : 71-77, 2005

27 Park JS, "Effects of capsaicin pretreatment on the function of mouse peritoneal macrophages" 22 : 39-49, 2000

28 Maisuo R, "Effects of a traditional Chinese herbal medicine, Kanzo-bushi-to, on the resistance of thermally injured mice infected with herpes simplex virus type 1" 16 : 855-863, 1994

29 Mauel J, "Effect of PGE2 and of agents that raise camp levels on macrophage activation induced by IFN-γ and TNF-α" 58 : 217-224, 1995

30 Mizuno M, "Differences in immunomodulating effects between wild and cultured Panax ginseng" 200 : 1672-1678, 1994

31 Betz JM, "Continuing studies on the ginsenoside content of commercial ginseng products by TLC, and HPLC II" University of Guelph 65-83, 1984

32 Akihisa T, "Azaphilones, Furanoisophthalides, and Amino Acids from the extracts of Monascus pilosus-fermented rice (red-mold rice) and their chemopreventive effects" 53 : 562-565, 2005

33 Furusawa E, "Anticancer potential of Viva-Natural, a dietary seaweed extract, on Lewis lung carcinoma in comparison with chemical immunomodulators and on cyclosporine-accelerated AKR leukemia" 46 : 343-348, 1989

34 Conolly KM, "Alteration of interleukin-1 production and the acute phase response following medication of adjuvant arthritic rats with cyclosporin-A or methtrexate" 10 : 717-728, 1988

35 Lee YS, "Activation of multiple effector pathways of immune system by the antineoplastic immunostimulator acidic polysaccharide ginsan isolated from Panax ginseng" 17 : 323-331, 1997

36 Green SJ, "Activated macrophages destroy intracellular Leishmania major amastigotes by an L-argininedependent killing mechanism" 144 : 278-283, 1990