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http://dx.doi.org/10.22246/jikm.2017.38.6.863

Anti-neoplastic and Anti-inflammatory Effects of Single and Mixed Extracts of Ulmus Davidiana and Oldenlandia Diffusa on Azoxymethane/dextran Sodium Sulfate-induced Colonic Neoplasms  

Lee, Seon-a (Dept. of Internal Medicine, College of Korean Medicine, Wonkwang University)
Baek, Dong-gi (Dept. of Internal Medicine, College of Korean Medicine, Wonkwang University)
Moon, Goo (Dept. of Internal Medicine, College of Korean Medicine, Wonkwang University)
Publication Information
The Journal of Internal Korean Medicine / v.38, no.6, 2017 , pp. 863-876 More about this Journal
Abstract
Objectives: The aim of this experimental study was to evaluate the anti-neoplastic and anti-inflammatory effects of single and mixed extracts of Ulmus davidiana (UD) and Oldenlandia diffusa (OD) on azoxymethane/dextran sodium sulfate (AOM/DSS)-induced colonic neoplasms in mice. Methods: AOM/DSS induces colitis-associated colonic neoplasms in mice. Mice were divided into seven groups: normal-no inducement and no treatment; control-colonic neoplasms with no treatment; UD-colonic neoplasms and treatment with UD; OD-colonic neoplasms and treatment with OD; UD1+OD1-colonic neoplasms and treatment with UD1 and OD1. UD1+OD2-colonic neoplasms and treatment with UD1 and OD2; UD2+OD1-colonic neoplasms and treatment with UD2 and OD1. Single and mixed preparations of UD and OD were applied to mice for six weeks. The colon length and weight and histopathologic changes of colon tissue were observed. Serum pro-inflammatory cytokines, including tumor necrosis factor-alpha ($TNF-{\alpha}$) and interleukin-6 (IL-6), were determined by enzyme-linked immunosorbent assay. The mRNA expression levels of Bax, Bcl-2, and interferon-gamma ($INF-{\gamma}$) were measured by RT-PCR. Results: The colon length was significantly increased in OD, UD1+OD2, and UD2+OD1 mice, and the colon weight was significantly decreased in OD and UD1+OD2 mice. The morphological change of colon epithelial cells was more suppressed in complex-treatment groups than in single-treatment groups. The inhibitory effect on inflammatory cell invasion was especially shown in UD1+OD2 mice. The serum level of the pro-inflammatory $TNF-{\alpha}$ was decreased in all complex-treatment groups, and the IL-6 level was decreased in UD1+OD1 mice. Single-treatment groups had an increase in the mRNA expression of the pro-apoptosis regulator Bax, and UD2+OD1 decreased the mRNA expression of the anti-apoptosis regulator Bcl-2. The mRNA expression of $INF-{\gamma}$ associated with inflammation was decreased in OD and UD1+OD2 mice. Conclusions: This study suggests that single and mixed extracts of Ulmus davidiana and Oldenlandia diffusa have anti-neoplastic and anti-inflammatory effects on AOM/DSS-induced colonic neoplasms in mice. Therefore, we conclude that UD, OD, and a mixture of UD and OD are potential therapeutic agents for colitis-associated colonic neoplasms.
Keywords
colonic neoplasms; tumor necrosis factor-alpha; interleukin-6; apoptosis;
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Times Cited By KSCI : 7  (Citation Analysis)
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1 Park JG, Park CI, Kim NG. Oncology. Seoul: Iljogak; 2003, p. 128-34, 160.
2 Maduro JH, Pras E, Willemse PH, de Vries EG. Acute and long-term toxicity following radio therapy alone or in combination with chemotherapy for locally advanced cervial cancer. Cancer Treat Rev 2003;29(6):471-88.   DOI
3 Suh N, Luyengi L, Fong HHS, Kinghorn AD, Pezzuto JM. Discovery of Natural Product Chemopreventive Agents Utilizing HL-60 Cell Differentiation as a Model. Anticancer Res 1995; 15(2):233-9.
4 Kang BS, Go UC, Kim GY, Kim SH, No SH, Park YG, et al. Bonchohak. Seoul: Yeonglimsa; 1991, p. 418-9.
5 Kim HS, Cho JH, Lee JM, Lee CH, Jang JB, Lee KS. Experimental Studies on Antimetastatic and Immunomodulating Effects of Ulmus davidiana. The Journal Of Oriental Gynecology 2010;23(1):1-11.
6 Han SI, Choi SD, Park YK, Kim GS, Kang BK. A Study on Antitumor Effect and Mechanism of Cortex ulmi pumilae Water Extract on HepG2 Hepatoma cell. Korean J Oriental Int Med 2000; 21(2):259-66.
7 Shin MG. Imsang-bonchohak. Seoul: Yeonglimsa; 2002, p. 569-70.
8 Choi YH. Research techniques for the cell cycle study. Exp Mol Med 2001;33:15-36.   DOI
9 Lee SJ, Gim HJ, Shim JH, Park HS, Kim BJ. Anti-Cancer Effects of Oldenlandia diffusa extract on WiDr human colorectal adenocarcinoma cells. Herbal Formula Science 2015;23(1):101-10.   DOI
10 Park JB, Sung NI, Lee JY, Hur IK, Kim SM, Nam JH, et al. Apoptotic Effect of Hedyotis Diffusa in Gastric Cancer Cell Lines. The DongGuk Journal of Medicine 2006;13(2):64-72.
11 Choi SH. Dongui-oncology. Seoul: Haenglim publishing company; 1995, p. 13.
12 A medical college of Seoul National University. Immunology. Seoul: Seoul National University publishing department; 1993, p. 303-9.
13 Jeong JW, Choi YH, Park C. Induction of Apoptosis by Ethanol Extract of Cnidium officinale in Human Leukemia U937 Cells through Activation of AMPK. J Life Sci 2015;25(11) :1255-64.   DOI
14 Joung BB, Kim YC. Study on Anti-Cancer Effects of Rhus Verniciflua Stokes Extracted with Sterile Distilled Water on Two Cholangiocarcinoma Cell Lines, SNU-1079 and SNU-1196. Korean J Oriental Int Med 2015;36(1):1-12.
15 Yang YL, Kim YJ, Kim KH, Oh EG. Separation of Glycoprotein and its Anticancer Immunostimulating Activity from Dried Barks of Slippery Elm(Ulmus parvifolia). KSBB Journal 2001;16(6):547-53.
16 Moon G, Jung BH, Kim BJ. Cancer, shared treatment of oriental and western medicine. Iksan: Wonkwang University publishing department; 1999, p. 253-7, 461-6.
17 Kim HA, IM SW, Lee WC. A study of the tendency of anti-cancer experimental study using herbal medicines. J of Kor Traditional Oncology 1998;4(1):211-32.
18 Hong ND, Kim NJ, No YS, Kim JS. Studies on the Pharmacological Activities and Constituents of Ulmi Cortex. Korean Journal of Pharmacognosy 1990;21(3):245.
19 Kim SH, Song GY, Ryu SY. Antitumor and antimetastatic activities of ursolic acid and asperuloside. JPPKM 1999;13(1):65-75.
20 Jeong KY, Kim ML. Physiological Activities of Ulmus pumila L. Extracts. Korean J Food Preserv 2012;19(1):104-9.   DOI
21 Raicht RF, Cohen BI, Fazzini EP, Sarwal AN, Takahashi M. Protective effect of plant sterols against chemically induced colon tumors in rats. Cancer Res 1980;40:403-5.
22 Gupta MB, Nath R, Srivastava N, Shanker K, Kishor K, Bhargava KP. Anti-inflammatory and antipyretic activities of beta-sitosterol. Planta Med 1980;39(2):157-63.   DOI
23 Jin MH, Park SY, Kang YG, Shim WS, Hur HS, Hong SH, et al. Anti-cancer Effects of Oldenlandia diffusa, Cremastra appendiculata and Fritillaria thunbergii on MDA-MB-231 Human Breast Cancer Cells. Korean J Oriental Int Med 2014;35(2):133-44.
24 No HJ, Moon G, Moon SJ, Won JH, Moon YH, Park RG. Study of Hedyotis Diffusa Methanol Extract on Anti-tumoral Effect and Mechanism. J of Kor Traditional Oncology 2000; 6(1):81-97.
25 Li H, Wu WK, Li ZJ, Chan KM, Wong CC, Ye CG, et al. 2,3,4,4,5-Pentamethoxy-trans-stilbene, a resveratrol derivative, inhibits colitis-associated colorectal carcinogenesis in mice. British J pharmacology 2010;160(6):1352-61.   DOI
26 Jung KW, Won YJ, Kong HJ, Oh CM, Cho HS, Lee DH, et al. Cancer Statistics in Korea: Incidence, Mortality, Survival, and Prevalence in 2012. Cancer Res Treat 2015;47(2):127-41.   DOI
27 Singh J, Hamid R, Reddy BS. Dietary Fat and Colon Cancer: Modulating Effect of Types and Amount of Dietary Fat on ras-p21 Function during Promotion and Progression Stages of Colon Cancer. Cancer Res 1997;57(2):253-8.
28 Kang HT, Lee SH, Kim SY, Kim MS, Shin WC, Sohn HY, et al. Anti-proliferative Activities of Solvent Fractions of Lees Extracts in Human Colorectal HCT116 Cells. J Life Sci 2014;24(9):967-72.   DOI
29 Hendrickson BA, Gokhale R, Cho JH. Clinical aspects and pathophysiology of inflammatory bowel disease. Clin Microbiol Rev 2002;15:79-94.   DOI
30 Lee YJ, Kim JE, Kwak MH, Go J, Son HJ, Kim DS. Toxicity of fermented soybean product (cheonggukjang) manufactured by mixed culture of Bacillus subtilis MC31 and Lactobacillus sakei 383 on liver and kidney of ICR mice. Lab Anim Res 2014;30:54-63.   DOI
31 Kim HM, Lee SO, Lee EH. The Nitric Oxide -Producing Properties of Ulmi Radicis Cortex Extract. Immunopharmacol Immunotoxicol 1999; 21(2):295-306.   DOI
32 Jung HJ. Anti-atherosclerosis effects of Ulmi Cortex extracts by anti-oxidant, anti-platelet, anti-inflammatory effects. Doctoral thesis of Dongguk University Graduate School 2010.
33 Jo YM. Anti-inflammatory Activity of Oledenlandia Diffusa through the Inhibition of NF-kB activation in Mouse Peritoneal Macrophage. Master's thesis of Wonkwang University Graduate School 2008.
34 Gross A, McDonnell JM, Korsmeyer SJ. BCL-2 family members and the mitochondria in apoptosis. Genes Dev 1999;13(15):1899-911.   DOI
35 Korsmeyer SJ. Regulators of cell death. Trends Genet 1995;11(3):101.   DOI
36 Hengartner MO. The biochemistry of apoptosis. Nature 2000;407:770-6.   DOI
37 Debatin KM. Apoptosis pathways in cancer and cancer therapy. Cancer Immunol Immunother 2004;53(3):153-9.   DOI
38 Li Z, Xu X, Huang Y, Ding L, Wang Z, Yu G, et al. Swainsonine activates mitochondria-mediated apoptotic pathway in human lung cancer A549 cells and retards the growth of lung cancer xenografts. Int J Biol Sci 2012;8(3):394-405.   DOI
39 Lee GH, Kim SH, Song HJ. Study on Antitumor Effect and Immune Response of Kilkyungtang and Kamikilkyungtang. JPPKM 1996;10(1):105-19.
40 Fesik SW. Insights into programmed cell death through structural biology. Cell 2000;103(2): 273-82.   DOI
41 Kim IJ, Lee GU, So HS, Park RK, Won JH, Moon G, et al. Study on caspases activation change of HL-60 cell apoptosis by hedyotis diffusa's methanol extract. The Journal of Traditional Korean Medicine 2000;10(1):255-69.
42 Park YK, Jung SJ, Jang TJ, Lee JH. Effects of Ulmi cortex extract on cell apoptosis in HT-29 human colon cancer cells. Kor J Herbology 2006; 21(4):51-8.
43 Rabson A, Roitt IM, Delves PJ. Really essential medical immunology. Oxford, UK: Blackwell publishing Ltd; 2005, p. 1-14.