American ginseng significantly reduced the progression of high-fatdiet-enhanced colon carcinogenesis in ApcMin/þmice

다국어 초록 (Multilingual Abstract)

Background: Colorectal cancer (CRC) is a leading cause of death worldwide. Chronic gut inflammation is recognized as a risk factor for tumor development, including CRC. American ginseng is a very commonly used ginseng species in the West.
Methods: A genetically engineered ApcMin/þ mouse model was used in this study. We analyzed the saponin composition of American ginseng used in this project, and evaluated its effects on the progression of high-fat-diet-enhanced CRC carcinogenesis.
Results: After oral ginseng administration (10e20 mg/kg/d for up to 32 wk), experimental data showed that, compared with the untreated mice, ginseng very significantly reduced tumor initiation and progression in both the small intestine (including the proximal end, middle end, and distal end) and the colon (all p < 0.01). This tumor number reduction was more obvious in those mice treated with a low dose of ginseng. The tumor multiplicity data were supported by body weight changes and gut tissue histology examinations. In addition, quantitative real-time polymerase chain reaction analysis showed that compared with the untreated group, ginseng very significantly reduced the gene expression of inflammatory cytokines, including interleukin-1a (IL-1a), IL-1b, IL-6, tumor necrosis factor-a, granulocyte-colony stimulating factor, and granulocyte-macrophage colony-stimulating factor in both the small intestine and the colon (all p < 0.01).
Conclusion: Further studies are needed to link our observed effects to the actions of the gut microbiome in converting the parent ginsenosides to bioactive ginseng metabolites. Our data suggest that American ginseng may have potential value in CRC chemoprevention.

참고문헌 (Reference)

1 McCarthy N, "Tumorigenesis: all together now" 13 : 148-149, 2013

2 Zhou Y, "Trends in the use of aspirin and nonsteroidal anti-inflammatory drugs in the general U.S. population" 23 : 43-50, 2014

3 Wang CY, "Traditional Chinese medicine: a treasured natural resource of anticancer drug research and development" 42 : 543-559, 2014

4 Jacoby RF, "The cyclooxygenase-2 inhibitor celecoxib is a potent preventive and therapeutic agent in the min mouse model of adenomatous polyposis" 60 : 5040-5044, 2000

5 Jin HR, "The antitumor natural compound falcarindiol promotes cancer cell death by inducing endoplasmic reticulum stress" 3 : e376-, 2012

6 De Robertis M, "The AOM/DSS murine model for the study of colon carcinogenesis: from pathways to diagnosis and therapy studies" 10 : 9-, 2011

7 Zhu J, "Suppression of local inflammation contributes to the neuroprotective effect of ginsenoside Rb1 in rats with cerebral ischemia" 202 : 342-351, 2012

8 Eun-Hwa Park, "Stereospecific anticancer effects of ginsenoside Rg3 epimers isolated from heat-processed American ginseng on human gastric cancer cell" 고려인삼학회 38 (38): 22-27, 2014

9 Wen XD, "Salvia miltiorrhiza (dan shen) significantly ameliorates colon inflammation in dextran sulfate sodium induced colitis" 41 : 1097-1108, 2013

10 National Cancer Institute, "SEER stat fact sheets: colon and rectum" NCI

11 Sun S, "Red notoginseng: higher ginsenoside content and stronger anticancer potential than Asian and American ginseng" 125 : 1299-1305, 2011

12 Wang CZ, "Red American ginseng: ginsenoside constituents and antiproliferative activities of heat-processed Panax quinquefolius roots" 73 : 669-674, 2007

13 Seung-Hoon Baek, "Recent Methodology in Ginseng Analysis" 고려인삼학회 36 (36): 119-134, 2012

14 Fichera A, "Quantitation of in vivo gene delivery by restriction enzyme PCR generated polymorphism" 69 : 188-192, 1997

15 Hasegawa H, "Proof of the mysterious efficacy of ginseng: basic and clinical trials: metabolic activation of ginsenoside: deglycosylation by intestinal bacteria and esterification with fatty acid" 95 : 153-157, 2004

16 Yun TK, "Preventive effect of ginseng intake against various human cancers: a case-control study on 1987 pairs" 4 : 401-408, 1995

17 Gu C, "Preliminary evaluation of the interactions of Panax ginseng and Salvia miltiorrhiza Bunge with 5-fluorouracil on pharmacokinetics in rats and pharmacodynamics in human cells" 41 : 443-458, 2013

18 Yun TK, "Panax ginsengda non-organ-specific cancer preventive?" 2 : 49-55, 2001

19 Liu S, "PI3K/AKT/mTOR signaling is involved in (e )-epigallocatechin-3-gallate-induced apoptosis of human pancreatic carcinoma cells" 41 : 629-642, 2013

20 Chen S, "Norcantharidin inhibits pre-replicative complexes assembly of HepG2 cells" 41 : 665-682, 2013

21 Day SD, "Linking inflammation to tumorigenesis in a mouse model of high-fat-diet-enhanced colon cancer" 64 : 454-462, 2013

22 Qi LW, "Isolation and analysis of ginseng: advances and challenges" 28 : 467-495, 2011

23 Paturi G, "Influence of dietary blueberry and broccoli on cecal microbiota activity and colon morphology in mdr1ae/e mice, a model of inflammatory bowel diseases" 28 : 324-330, 2012

24 Hofseth LJ, "Inflammation, cancer, and targets of ginseng" 137 : S183-S185, 2007

25 Derry MM, "Grape seed extract efficacy against azoxymethaneinduced colon tumorigenesis in A/J mice: interlinking miRNA with cytokine signaling and inflammation" 6 : 625-633, 2013

26 Khan R, "Glycyrrhizic acid suppresses the development of precancerous lesions via regulating the hyperproliferation, inflammation, angiogenesis and apoptosis in the colon of Wistar rats" 8 : e56020-, 2013

27 Qi LW, "Ginsenosides from American ginseng: chemical and pharmacological diversity" 72 : 689-699, 2011

28 Christensen LP, "Ginsenosides chemistry, biosynthesis, analysis, and potential health effects" 55 : 1-99, 2009

29 Wang CZ, "Ginsenoside compound K, not Rb1, possesses potential chemopreventive activities in human colorectal cancer" 40 : 1970-1976, 2012

30 Park EY, "Efficacy comparison of Korean ginseng and American ginseng on body temperature and metabolic parameters" 42 : 173-187, 2014

31 Qi LW, "Diagnostic ion filtering to characterize ginseng saponins by rapid liquid chromatography with time-offlight mass spectrometry" 1230 : 93-99, 2012

32 Wang CZ, "Detection of adulteration of notoginseng root extract with other panax species by quantitative HPLC coupled with PCA" 57 : 2363-2367, 2009

33 Tawab MA, "Degradation of ginsenosides in humans after oral administration" 31 : 1065-1071, 2003

34 Lewis B, "Crohn’s disease-like reaction predicts favorable prognosis in colitis-associated colorectal cancer" 19 : 2190-2198, 2013

35 Garcia Rodriguez LA, "Coxibs: pharmacology, toxicity and efficacy in cancer clinical trials" 191 : 67-93, 2013

36 National Cancer Institute, "Colon and rectal cancer" NCI

37 Foersch S, "Colitis and colorectal cancer" 30 : 469-476, 2012

38 Benbrook DM, "Chemoprevention of colon and small intestinal tumorigenesis in APCmin/þ mice by SHetA2 (NSC721689) without toxicity" 6 : 908-916, 2013

39 Mohammed A, "Chemoprevention of colon and small intestinal tumorigenesis in APCMin/þ mice by licofelone, a novel dual 5-LOX/COX inhibitor: potential implications for human colon cancer prevention" 4 : 2015-2026, 2011

40 Shibata S, "Chemistry and cancer preventing activities of ginseng saponins and some related triterpenoid compounds" 16 : S28-S37, 2001

41 Chun-Su Yuan, "Chemical and Pharmacological Studies of Saponins with a Focus on American Ginseng" 고려인삼학회 34 (34): 160-167, 2010

42 Siegel R, "Cancer statistics, 2014" 64 : 104-117, 2014

43 Xiaoguang C, "Cancer chemopreventive and therapeutic activities of red ginseng" 60 : 71-78, 1998

44 Yuan CS, "Brief communication: American ginseng reduces warfarin’s effect in healthy patients: a randomized, controlled trial" 141 : 23-27, 2004

45 Wan JY, "Biotransformation and metabolic profile of American ginseng saponins with human intestinal microflora by liquid chromatography quadrupole time-of-flight mass spectrometry" 1286 : 83-92, 2013

46 Madka V, "Anti-inflammatory phytochemicals for chemoprevention of colon cancer" 13 : 542-557, 2013

47 Qi LW, "American ginseng: potential structure-function relationship in cancer chemoprevention" 80 : 947-954, 2010

48 Jin Y, "American ginseng suppresses colitis through p53-mediated apoptosis of inflammatory cells" 3 : 339-347, 2010

49 Dougherty U, "American ginseng suppresses Western dietpromoted tumorigenesis in model of inflammation-associated colon cancer: role of EGFR" 11 : 111-121, 2011

50 Zamir K. Punja, "American Ginseng: Research Developments, Opportunities, and Challenges" 고려인삼학회 35 (35): 368-374, 2011

51 Poudyal D, "A hexane fraction of American ginseng suppresses mouse colitis and associated colon cancer: anti-inflammatory and proapoptotic mechanisms" 5 : 685-696, 2012

52 Oh GS, "20(S)-Protopanaxatriol, one of ginsenoside metabolites, inhibits inducible nitric oxide synthase and cyclooxygenase-2 expressions through inactivation of nuclear factor-kappaB in RAW 264.7 macrophages stimulated with lipopolysaccharide" 205 : 23-29, 2004