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Reduction of Intestinal Polyp Formation in Min Mice Fed a High-Fat Diet with Aloe Vera Gel Extract

  • Chihara, Takeshi (Fujita Memorial Nanakuri Institute, Fujita Health University) ;
  • Shimpo, Kan (Fujita Memorial Nanakuri Institute, Fujita Health University) ;
  • Beppu, Hidehiko (Fujita Memorial Nanakuri Institute, Fujita Health University) ;
  • Tomatsu, Akiko (Fujita Memorial Nanakuri Institute, Fujita Health University) ;
  • Kaneko, Takaaki (Fujita Memorial Nanakuri Institute, Fujita Health University) ;
  • Tanaka, Miyuki (Functional Food Research Department, Food Science and Technology Institute, Morinaga Milk Industry Co., Ltd.) ;
  • Yamada, Muneo (Functional Food Research Department, Food Science and Technology Institute, Morinaga Milk Industry Co., Ltd.) ;
  • Abe, Fumiaki (Functional Food Research Department, Food Science and Technology Institute, Morinaga Milk Industry Co., Ltd.) ;
  • Sonoda, Shigeru (Fujita Memorial Nanakuri Institute, Fujita Health University)
  • Published : 2013.07.30

Abstract

Aloe vera gel supercritical $CO_2$ extract (AVGE) has been shown to contain five phytosterols, reduce visceral fat accumulation, and influence the metabolism of glucose and lipids in animal model experiments. Recent epidemiologic studies have shown that obesity is an established risk factor for several cancers including colorectal cancer. Therefore, we examined the effects of AVGE on intestinal polyp formation in Apc-deficient Min mice fed a high-fat diet. Male Min mice were divided into normal diet (ND), high fat diet (HFD), low dose AVGE (HFD+LAVGE) and high dose AVGE (HFD+HAVGE) groups. The ND group received AIN-93G diet and the latter 3 groups were given modified high-fat AIN-93G diet (HFD) for 7 weeks. AVGE was suspended in 0.5% carboxymethyl cellulose (CMC) and administered orally to mice in HFD+LAVGE and HFD+HAVGE groups every day (except on Sunday) for 7 weeks at a dose of 3.75 and 12.5 mg/kg body weight, respectively. ND and HFD groups received 0.5% CMC alone. Between weeks 4 and 7, body weights in the HFD and HFD+LAVGE groups were reduced more than those in the ND group. However, body weights were not reduced in the HFD+HAVGE group. Mice were sacrificed at the end of the experiment and their intestines were scored for polyps. No significant differences were observed in either the incidence and multiplicity of intestinal polyps (${\geq}0.5$ mm in a diameter) among the three groups fed HFD. However, when intestinal polyps were categorized by their size into 0.5-1.4, 1.5-2.4, or ${\geq}2.5$ mm, the incidence and multiplicity of large polyps (${\geq}2.5$ mm) in the intestine in the HFD+HAVGE group were significantly lower than those in the HFD group. We measured plasma lipid (triglycerides and total cholesterol) and adipocytokine [interleukin-6 and high molecular weight (HMW) adiponectin] levels as possible indicators of mechanisms of inhibition. The results showed that HMW adiponectin levels in the HFD group were significantly lower than those in the ND group. However, the levels in the HFD+HAVGE group were significantly higher than those in the HFD group. These results indicate that HAVGE reduced large-sized intestinal polyps and ameliorated reduction in plasma HMW adiponectin levels in Min mice fed HFD.

Keywords

Apc-deficient Min mice;Aloe vera gel extract (AVGE);intestinal polyp formation

References

  1. Arita Y, Kihara S, Ouchi N, et al (1999). Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophy Res Commun, 257, 79-83. https://doi.org/10.1006/bbrc.1999.0255
  2. Baltgalvis KA, Berger FG, Pena MMO, Davis JM, Carson JA (2009). The interaction of a high-fat diet and regular moderate intensity exercise on intestinal polyp development in ApcMin/+ mice. Cancer Prev Res (Phila), 2, 641-9. https://doi.org/10.1158/1940-6207.CAPR-09-0017
  3. Battle TE, Frank DA (2002). The role of STATs in apoptosis. Curr Mol Med, 2, 381-92. https://doi.org/10.2174/1566524023362456
  4. Berg AH, Combs TP, Scherer PE (2002). ACRP30/adiponectin: an adipokine regulating glucose and lipid metabolism. Trends Endocrinol Metab, 13, 84-9. https://doi.org/10.1016/S1043-2760(01)00524-0
  5. Bianchini F, Kaaks R, Vainio H (2002). Overweight, obesity, and cancer risk. Lancet Oncol, 3, 565-74. https://doi.org/10.1016/S1470-2045(02)00849-5
  6. Bobbert T, Rochlitz H, Wegewitz U, et al (2005). Changes of adiponectin oligomer composition by moderate weight reduction. Diabetes, 54, 2712-9. https://doi.org/10.2337/diabetes.54.9.2712
  7. Brozek W, Bises G, Girsch T, et al (2005). Differentiationdependent expression and mitogenic action of interleukin-6 in human colon carcinoma cells: relevance for tumor progression. Eur J Cancer, 41, 2347-54. https://doi.org/10.1016/j.ejca.2005.07.014
  8. Chung J, Kim MS, Han SN (2011). Diet-induced obesity leads to decreased hepatic iron storage in mice. Nutr Res, 31, 915-21. https://doi.org/10.1016/j.nutres.2011.09.014
  9. Fenton JI, Birmingham JM, Hursting SD, Hord NG (2008). Adiponectin blocks multiple signaling cascades associated with leptin-induced cell proliferation in ApcMin/+ colon epithelial cells. Int J Cancer, 122, 2437-45. https://doi.org/10.1002/ijc.23436
  10. Fenton JI, Hursting SD, Perkins SN, Hord NG (2006). Interleukin-6 production induced by leptin treatment promotes cell proliferation in an Apc(Min/+) colon epithelial cell line. Carcinogenesis, 27, 1507-15. https://doi.org/10.1093/carcin/bgl018
  11. Fenton JI, Hord NG, Lavigne JA, Perkins SN, Hursting SD (2005). Leptin, insulin-like growth factor-1, and insulin-like growth factor-2 are mitogens in ApcMin/+ but not Apc+/+ colonic epithelial cell lines. Cancer Epidemiol Biomarkers Prev, 14, 1646-52. https://doi.org/10.1158/1055-9965.EPI-04-0916
  12. Fujisawa T, Endo H, Tomimoto A, et al (2008). Adiponectin suppresses colorectal carcinogenesis under the high-fat diet condition. Gut, 57, 1531-8. https://doi.org/10.1136/gut.2008.159293
  13. Hara K, Yamauchi T, Imai Y, et al (2007). Reduced adiponectin level is associated with severity of coronary artery disease. Int Heart J, 48, 149-53 https://doi.org/10.1536/ihj.48.149
  14. Jacoby RF, Marshall DJ, Newton MA, et al (1996). Chemoprevention of spontaneous intestinal adenomas in the Apc Min mouse model by the nonsteroidal anti-inflammatory drug piroxcam. Cancer Res, 56, 710-4.
  15. Larsson SC, Wolk A (2007). Obesity and colon and rectal cancer risk: a meta-analysis of prospective studies. Am J Clin Nutr, 86, 556-65.
  16. Misawa E, Tanaka M, Nomaguchi K, et al (2012a). Oral ingestion of Aloe vera phytosterols alters hepatic gene expression profiles and ameliorates obesity-associated metabolic disorders in Zucker diabetic fatty rats. J Agric Food Chem, 60, 2799-806. https://doi.org/10.1021/jf204465j
  17. Misawa E, Tanaka M, Nabeshima K, et al (2012b). Administration of dried Aloe vera gel powder reduced body fat mass in diet-induced obesity (DIO) rats. J Nutr Sci Vitaminol, 58, 195-201. https://doi.org/10.3177/jnsv.58.195
  18. Misawa E, Tanaka M, Nomaguchi K, et al (2008). Administration of phytosterols isolated from Aloe vera gel reduce visceral fat mass and improve hyperglycemia in Zucker diabetic fatty (ZDF) rats. Obes Res Clin Pract, 2, 239-45. https://doi.org/10.1016/j.orcp.2008.06.002
  19. Moser AR, Pitot HC, Dove WF (1990). A dominant mutation that predisposes to multiple intestinal neoplasia in the mouse. Science, 247, 322-4. https://doi.org/10.1126/science.2296722
  20. Mutoh M, Teraoka N, Takasu S, et al (2011). Loss of adiponectin promotes intestinal carcinogenesis in Min and wild-type mice. Gastroenterology, 140, 2000-8. https://doi.org/10.1053/j.gastro.2011.02.019
  21. Niho N, Mutoh M, Takahashi M, et al (2005). Concurrent suppression of hyperlipidemia and intestinal polyp formation by NO-1886, increasing lipoprotein lipase activity in Min mice. Proc Natl Acad Sci USA, 102, 2970-4. https://doi.org/10.1073/pnas.0500153102
  22. Niho N, Takahashi M, Kitamura T, et al (2003). Concomitant suppression of hyperlipidemia and intestinal polyp formation in Apc-deficient mice by peroxisome proliferator-activated receptor ligands. Cancer Res, 63, 6090-5.
  23. Nomaguchi K, Tanaka M, Misawa E, et al (2011). Aloe vera phytosterols act as ligands for PPAR and improve the expression levels of PPAR target genes in the livers of mice with diet-induced obesity. Obes Res Clin Pract, 5, 190-201. https://doi.org/10.1016/j.orcp.2011.01.002
  24. Okamoto Y, Kihara S, Funahashi T, Matsuzawa Y, Libby P (2006). Adiponectin: a key adipocytokine in metabolic syndrome. Clin Sci (Lond), 110, 267-78. https://doi.org/10.1042/CS20050182
  25. Otake S, Takeda H, Suzuki Y, et al (2005). Association of visceral fat accumulation and plasma adiponectin with colorectal adenoma: evidence for participation of insulin resistance. Clin Cancer Res, 11, 3642-6. https://doi.org/10.1158/1078-0432.CCR-04-1868
  26. Otani K, Kitayama J, Yasuda K, et al (2010). Adiponectin suppresses tumorigenesis in Apc Min/+ mice. Cancer Lett, 288, 177-82. https://doi.org/10.1016/j.canlet.2009.06.037
  27. Pajvani UB, Du X, Combs TP, et al (2003). Structure-function studies of the adipocyte-secreted hormone Acrp30/ adiponectin. Implications for metabolic regulation and bioactivity. J Biol Chem, 278, 9073-85. https://doi.org/10.1074/jbc.M207198200
  28. Pajvani UB, Hawkins M, Combs TP, et al (2004). Complex distribution, not absolute amount of adiponectin, correlates with thiazolidinedione-mediated improvement in insulin sensitivity. J Biol Chem, 279, 12152-62. https://doi.org/10.1074/jbc.M311113200
  29. Perez YY, Jimenez-Ferrer E, Zamilpa A, et al (2007). Effect of a polyphenol-rich extract from Aloe vera gel on experimentally induced insulin resistance in mice. Am J Chin Med, 35, 1037-46. https://doi.org/10.1142/S0192415X07005491
  30. Rajasekaran S, Ravi K, Sivagnanam K, Subramanian S (2006). Beneficial effects of Aloe vera leaf gel extract on lipid profile status in rats with streptozotocin diabetes. Clin Exp Pharmacol Physiol, 33, 232-7. https://doi.org/10.1111/j.1440-1681.2006.04351.x
  31. Rowe TD, Parks LM (1941). A phytochemical study of Aloe vera leaf. J Am Pharm Assoc, 30, 262-6.
  32. Seino Y, Hirose H, Saito I, Itoh H (2007). High molecular weight multimer form of adiponectin as a useful marker to evaluate insulin resistance and metabolic syndrome in Japanese men. Metabolism, 56, 1493-9. https://doi.org/10.1016/j.metabol.2007.06.015
  33. Shelton RM (1991). Aloe vera. Its chemical and therapeutic properties. Int J Dermatol, 30, 679-83. https://doi.org/10.1111/j.1365-4362.1991.tb02607.x
  34. Steiner H, Godoy-Tundidor S, Rogatsch H, et al (2003). Accelerated in vivo growth of prostate tumors that up-regulate interleukin-6 is associated with reduced retinoblastoma protein expression and activation of the mitogen-activated protein kinase pathway. Am J Pathol, 162, 655-63. https://doi.org/10.1016/S0002-9440(10)63859-X
  35. Takahashi H, Takayama T, Yoneda K, et al (2009). Association of visceral fat accumulation and plasma adiponectin with rectal dysplastic aberrant crypt foci in a clinical population. Cancer Sci, 100, 29-32. https://doi.org/10.1111/j.1349-7006.2008.00994.x
  36. Tanaka M, Misawa E, Ito Y, et al (2006). Identification of five phytosterols from Aloe vera gel as anti-diabetic compounds. Biol Pharm Bull, 29, 1418-22. https://doi.org/10.1248/bpb.29.1418
  37. Tanaka M, Yamada M, Toida T, Iwatsuki, K (2012). Safety evaluation of supercritical carbon dioxide extract of Aloe vera gel. J Food Sci, 77, 2-9.
  38. Ushida Y, Sekine K, Kuhara T, et al (1998). Inhibitory effects of bovine lactoferrin on intestinal polyposis in the ApcMin mouse. Cancer Lett, 134, 141-5. https://doi.org/10.1016/S0304-3835(98)00249-3
  39. Vogler BK, Ernst E (1999). Aloe vera: a systematic review of its clinical effectiveness. Br J Gen Prct, 49, 823-8.
  40. Waki H, Yamauchi T, Kamon J, et al (2003). Impaired multimerization of human adiponectin mutants associated with diabetes. J Biol Chem, 278, 40352-63. https://doi.org/10.1074/jbc.M300365200
  41. Whitehead JP, Richards AA, Hickman IJ, Macdonald GA, Prins JB (2006). Adiponectin-a key adipokine in the metabolic syndrome. Diabetes Obes Metabol, 8, 264-80. https://doi.org/10.1111/j.1463-1326.2005.00510.x
  42. Yamada M, Nomaguchi K, Toida T, et al (2011). Safety evaluation of Aloe vera gel supercritical $CO_2$ extract in obese men with intake for 12 weeks-Exploratory data analysis: effect of Aloe vera gel supercritical $CO_2$ extract on liver function in obese men with abnormal serum alanine aminotransferase (ALT) values. Prog Med, 31, 1157-62.

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