면역에 대한 관심은 점차 증가하는 추세이며, 식물유래 천연물을 이용한 면역기능 증강에 관련된 연구 역시 활발히 진행되고 있다. 왕느릅나무 껍질은 줄기 혹은 뿌리의 껍질을 뜻하며 전통적으로 동·서양 할 것 없이 항염, 진통, 항암, 상처치료에 사용되어 왔다. 본 연구는 왕느릅나무 열수 추출물(Ulmus macrocarpa water extract, UMWE)이 면역기능에 끼치는 영향을 조사하기 위해 실시되었다. 실험은 UMWE를 농도 100 mg/kg 또는 200 mgkg로 식이한 군, UMW를 농도 100 mg/kg 또는 200 mg/kg으로 식이하면서 면역억제물질인 cyclophosphamide(CY, 120 mg/kg)를 투여한 군, CY만을 투여한 군, 아무 것도 처리하지 않은 비처리군, 총 6개 군으로 나누어 2주간 매일 식이하면서 진행하였다. 각 군에서 획득한 비장지수와 비장세포 지수를 비교하였을 때 UMWE 식이가 CY에 의한 비장세포의 감소를 완화시키는 것으로 나타났으며, in vitro 실험에서 MTT방법과 7-amino-actinomycin D 방법을 통해 비장세포의 생존을 유지하며 사멸을 지연하는 것이 확인되었다. 또한, UMWE는 YAC-1에 대한 비장 NK 세포 활성을 면역억제제 CY가 존재하는 조건에서도 정상적으로 유지시켜 면역기능 유지에 영향을 주는 것으로 나타났다.
Ulmi cortex is the elm bark or root bark of Ulmus macrocarpa Hance and has been used as an ingredient of traditional medicine for anti-inflammatory, analgesic, anti-cancer and wound healing on both the East and the West. This study investigated whether the Ulmus macrocarpa Hance Water extract (UMWE) has the in vivo and in vitro immune activating effect. Animals were orally administrated for 14 days as follows: no treat group with distilled water, cyclophosphamide (CY) group with 120 mg/kg of CY, UMWE 100+CY group with 100 mg/kg of UMWE and 120 mg/kg of CY, UMWE 200+CY group with 200 mg/kg of UMWE and 120 mg/kg of CY, UMWE 100 group with 100 mg/kg of UMWE and UMWE 200 group with 200 mg/kg of UMWE. The immunosuppressive drug CY was intraperitoneally injected to induce immune suppression. Spleen indices showed small changes in CY injected groups but splenocyte indices showed greater decrease in the same groups. However, UMWE appeared to relieve CY’s immunosuppression. UMWE also delayed in vitro splenocyte death increasing its longevity. These data obtained by MTT assay and 7-amino-actinomycin D which stains preferentially dead than live cells. UMWE alone did not show cytotoxicity based on its apoptototic effect on splenocytes in vitro and in vivo. Splenic NK cell activity was maintained by UMWE under the presence of CY in vitro. The data indicated that UMWE protects splenocytes from the immunosuppressive drug CY under in vitro and in vivo conditions.
Choi, W. H., Oh, Y. S., Ahn, J. Y., Kim, S. R. and Ha, T. Y. 2005. Antioxidative and protective effect of Ulmus davidiana var. japonica extracts on glutamate-induced cytotoxicity in PC 12 cells. Kor. J. Food Scl. Technol. 37, 479-483.
Cesta, M. F. 2006. Normal structure, function, and histology of the spleen. Toxicol. Pathol. 34, 455-465.
Collins, F. M., Congdon, C. C. and Morrison, N. E. 1975. Growth of Mycobacterium bovis (BCG) in T lymphocyte-depleted mice. Infect. Immun. 11, 57-64.
Dranoff, G. 2004. Cytokines in cancer pathogenesis and cancer therapy. Nature Reviews Cancer 4, 11-22.
Emadi, A. Jones, R. J. and Brodsky, R. A. 2009. Cyclophosphamide and cancer: golden anniversary. Nat. Rev. Clin. Oncol. 6, 638-647.
Fetterhoff, T. J., Holland, S. P. and Wile, K. J. 1993. Fluorescent detection of non-viable cells in fixed cell preparations. Cytometry Suppl. 6, 27.
Goldstein, M. Roos, W. P. and Kaina, B. 2008. Apoptotic death induced by the cyclophosphamide analogue mafosfamide in human lymphoblastoid cells: contribution of DNA replication, transcription inhibition, and Chk/p53 signaling. Toxicol. Appl. Pharmacol. 229, 20-32.
Huang, G. C., Wu, L. S., Chen, L. G., Yang, L. L. and Wang, C. C. 2007. Immuno-enhancement effects of Huang Qi Liu Yi Tang in a murine model of cyclophosphamide-induced leucopenia. J. Erthnopharmacol. 109, 229-235.
Huyan, X. H., Lin, Y. P., Gao, T., Chen, R. Y. and Fan, Y. M. 2011. Immunosuppressive effect of cyclophosphamide on white bloodcells and lymphocyte subpopulations from peripheral blood of Balb/c mice. International Immunopharmacol. 11, 1293-1297.
Hamerman, J. A., Ogasawara, K. and Lanier, L. L. 2005. NK cells in innate immunity. Current Opinion in Immunol. 17, 29-35.
Jeong, J. T. 2007. An analysis of the research of pharmacological effects for the ulmus davidiana planch. dissertation, Chosun University, Gwangju, Korea.
Jeong, K. Y. and Kim, M. L. 2012. Physiological activities of Ulmus pumila L. extracts. Kor. J. Food Preserv. 19, 104-109.
Kim, K. H., Kang, I. K., Kang, E. J., Yang, E. K. and Park, S. N. 2004. A research trend of natural product on well-being industry. J. Soc. Cosmet. 30, 329-343.
Koopman, G., Reutelingsperger, C. P. M., Kuijten, G. A. M., KeeHnen, R. M. J., Pals, S. T. and van Oers, M. H. J. 1994. Annexine V for flow cytometric detection of phosphatidylserine expression on B Cells undergoing apoptosis. Blood. 84, 1415-1420.
Lee, Y. J. and Han, J. P. 2000. Antioxidative activities and nitrite scavenging abilities of extracts from Ulmus devidiana. J. Kor. Soc. Food Sci. Nutr. 29, 893-899.
Lee, S. E., Kim, Y. S., KIm, J. E., Bang, J. K. and Seong, N. S. 2004. Antioxidant activity of Ulmus davidiana var.japonica N. and Hemipteleae davidii P. Kor. J. Medicinal Crop. Sci. 12, 321-327.
Lee, E. H., Park, C. W. and Jung, Y. J. 2013. Anti-inflammatory and immune-modulating effect of Ulmus davidiana var. japonica Nakai extract on a macrophage cell line and immune cells in the mouse small intestine. J. Ethnopharmacol. 146, 608-613.
Lee, H. Y., Kim, C. K., Sung, T. K., Mun, T. K. and Lim, C. J. 1992. Antibacterial activity of Ulmus pumila L. extract. Kor. J. Appl. Microbiol. Biotechnol. 20, 1-5.
Lee, K. H., Cho, C. H. and Yoon, W. H. 2004. In vivo antitumor activity of mansonone E isolated from Ulmus davidiana var. japonica NAKAI. Kor. J. Pharmacogn. 35, 199-202.
Lafreniere, R. and Rosenberg, S. A. 1985. Successful immunotherapy of murine experimental hepatic metastases with lymphokine-activated killer cells and recombinant interleukin 2. Cancer Res. 45, 3735-3741.
Leung, H. Y., Ma, C. W., Tang, Q. T. and Ko, K. M. 2011. Long-Term treatment with a compound polysaccharide-based health product (InfinitusPolysac Plus) enhances innate and adaptive immunity in mice. Chinese Medicine 2, 178-185.
Mosmann, T. 1983. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J. Immunol. Methods 65, 55-63.
Pak, C. H. 1999. Korean Folk Medicine, pp. 53, PNU Press, Korea.
Park, J. S., Shim, C. J., Jung, J. H., Lee, G. H., Sung, C. K. and Oh, M. J. 1999. Antimicrobial activity of ulmi cortex extracts. J. Kor. Soc. Food Sci. Nutr. 28, 1022-1028.
Parham, P. 2009. The Immune System, pp 21-22, 3rd edition. Garland Science: New York, NY, USA.
Seo, B. I., Ju, Y. S., Choi, H. Y., Park, Roh, S. S., Koo, J. S., Kim, J. J. and Kim, D. Y. 2011. Illustrated Book of Herbal Plants in Oriental Medicine, pp. 353-357, DaeWondang, Korea.
Schmid, I., Uittenbogaart, C. H., Krall, W. J., Braun, J. and Giorgi, J. V. 1992. Dead cell discrimination with 7-amino-actinomycin D in combination with dual color immunofluorescence in single laser flow cytometry. Cytometry 13, 204-208.
Shimizu, S. 2004. The Laboratory mouse. Elsevier.
Wang, J., Tong, X., Li, P., Cao, H. and Su, W. 2012. Immuno-enhacement effects of ShenqiFuzheng Injection on cyclophosphamide-induced immunosuppression in Balb/c mice. J. Ethnopharmacol. 139, 769-775.
Winkelstein, A. 1973. Mechanism of Immunosuppression : Effects of Cyclophosphamide on Cellular Immunity. Blood 41, 273-284.
Yang, Y. L., Kim, Y. J., Kim, K. H. and Oh, E. G. 2001. Separation of glycoprotein and its anticancer immunostimulating activity from dried barks of slippery elm [Ulmus parvifolia]. Kor. J. Biotechnol. Bioeng. 16, 547-553.
Yang, S. X. and Li, X. Yu. 1990. Enhancement of T lymphocyte proliferation and suppression of antibody producing cell formation by methionine-enkephalin. Acta Pharmacologica Sinica 11, 355-359.