DOI QR코드

DOI QR Code

Isolation of Intestinal Glucose Uptake Inhibitor from Punica granatum L.

  • Kim, Hye-Kyung (Department of Food and Biotechnology, Hanseo University) ;
  • Baek, Soon-Sun (R&D Headquarters Ginseng Research Institute, Korea Ginseng Corporation) ;
  • Cho, Hong-Yon (Department of Food and Biotechnology, College of Science and Technology, Korea University)
  • 투고 : 2011.03.31
  • 심사 : 2011.06.03
  • 발행 : 2011.06.30

초록

Inhibition of intestinal glucose uptake is beneficial in reducing the blood glucose level for diabetes. To search for an effective intestinal glucose uptake inhibitor from natural sources, 70 native edible plants, fruits and vegetables were screened using Caco-2 cells and fluorescent D-glucose analog 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-D-glucose (2-NBDG). A compound that was able to inhibit glucose uptake was isolated from methanol extract of Punica granatum L. and called PG-1a. PG-1a appears to be a phthalic acid-diisononyl ester- like compound (PDE) with molecular weight of 418. The inhibitory effect of PG-1a on intestinal glucose uptake was dose-dependent with 89% inhibition at $100\;{\mu}g$/mL. Furthermore, the intestinal glucose uptake inhibitory effect of PG-1a was 1.2-fold higher than phlorizin, a well known glucose uptake inhibitor. This study suggests that PG-1a could play a role in controlling the dietary glucose absorption, and that PG-1a can effectively improve the diabetic condition, and may be used as an optional therapeutic and preventive agent.

키워드

참고문헌

  1. Wysham CH. 2010. New perspectives in type 2 diabetes, cardiovascular risk, and treatment goals. Postgrad Med 122: 52-60.
  2. Jenkins DJ, Kendall CW, Augustin LS, Martini MC, Axelsen M, Faulkner D, Vidgen E, Parker T, Lau H, Connelly PW, Teitel J, Singer W, Vandenbroucke AC, Leiter LA, Josse R. 2002. Effect of wheat bran on glycemic control and risk factors for cardiovascular disease in type 2 diabetes. Diabetes Care 25: 1522-1528. https://doi.org/10.2337/diacare.25.9.1522
  3. Hara Y, Honda M. 1990. The inhibition of $\alpha$-amylase by tea polyphenols. Agric Biol Chem 54: 1939-1945. https://doi.org/10.1271/bbb1961.54.1939
  4. Kim YM, Wang MH, Rhee HI. 2004. A novel alpha-glucosidase inhibitor from pine bark. Carbohydr Res 339: 715-717. https://doi.org/10.1016/j.carres.2003.11.005
  5. Bischoff H. 1994. Pharmacology of alpha-glucosidase inhibition. Eur J Clin Invest 3: 3-10.
  6. Anesini C, Perez C. 1993. Screening of plants used in Argentine folk medicine for antimicrobial activity. J Ethnopharmacol 39: 119-128. https://doi.org/10.1016/0378-8741(93)90027-3
  7. Ponce-Macotela M, Navarro-Alegria I, Martinez-Gordillo MN, Alvarez-Chacon R. 1994. In vitro effect against Giardia of 14 plant extracts. Rev Invest Clin 46: 343-347.
  8. Zhang J, Zhan B, Yao X, Gao Y, Shong J. 1995. Antiviral activity of tannin from the pericarp of Punica granatum L. against genital Herpes virus in vitro. Zhongguo Zhong Yao Za Zhi 20: 5586-5588.
  9. Mavlyanov SM, Islambekov SY, Karimdzhanov AK, Ismailov AI. 1997. Polyphenol of pomegranate peels show marked anti-tumor and anti-viral action. Khim Prir Soedin 33: 124-126.
  10. Jafri MA, Aslam M, Javed K, Singh SL. 2000. Effect of Punica granatum Linn. (flowers) on blood glucose level in normal and alloxan-induced diabetic rats. J Ethnopharmacol 70: 309-314. https://doi.org/10.1016/S0378-8741(99)00170-1
  11. Aviram M, Dornfeld L, Rosenblat M, Volkova N, Kaplan M, Coleman R, Hayek T, Presser D, Fuhrman B. 2000. Pomegranate juice consumption reduces oxidative stress, atherogenic modifications to LDL, and platelet aggregation: studies in humans and in atherosclerotic apolipoprotein E-deficient mice. Am J Clin Nutr 71: 1062-1076.
  12. Mahraoui L, Rodolosse A, Barba A, Dussaulx E, Zweibaum A, Rousset M, Brot-Laroche E. 1994. Presence and differential expression of SGLT1, GLUT1, GLUT2, GLUT3 and GLUT5 hexose-transporter mRNAs in Caco-2 cell clones in relation to cell growth and glucose consumption. Biochem J 298: 629-633. https://doi.org/10.1042/bj2980629
  13. Leira F, Louzao MC, Vieites JM, Botana LM, Vieytes MR. 2002. Fluorescent microplate cell assay to measure uptake and metabolism of glucose in normal human lung fibroblasts. Toxicol In Vitro 16: 267-273. https://doi.org/10.1016/S0887-2333(02)00002-4
  14. Zou C, Wang Y, Shen Z. 2005. 2-NBDG as a fluorescent indicator for direct glucose uptake measurement. J Biochem Biophys Methods 64: 207-215. https://doi.org/10.1016/j.jbbm.2005.08.001
  15. Alonso-Castro AJ, Miranda-Torres AC, Gonzalez-Chavez MM, Salazar-Olivo L. 2008. Cecropia obtusifolia Bertol and its active compound, chlorogenic acid, stimulate 2-NBDglucose uptake in both insulin-sensitive and insulinresistant 3T3 adipocytes. J Ethnopharmacol 120: 458-464. https://doi.org/10.1016/j.jep.2008.09.019
  16. Alonso-Castro AJ, Salazar-Olivo LA. 2008. The anti-diabetic properties of Guazuma ulmifolia Lam are mediated by the stimulation of glucose uptake in normal and diabetic adipocytes without inducing adipogenesis. J Ethnopharmacol 118: 252-256. https://doi.org/10.1016/j.jep.2008.04.007
  17. Gaudreault N, Scriven DR, Laher I, Moore ED. 2008. Subcellular characterization of glucose uptake in coronary endothelial cells. Microvasc Res 75: 73-82. https://doi.org/10.1016/j.mvr.2007.04.006
  18. Leira F, Louzao MC, Vieites JM, Botana LM, Vieytes MR. 2002. Fluorescent microplate cell assay to measure uptake and metabolism of glucose in normal human lung fibroblasts. Toxicol In Vitro 16: 267-273. https://doi.org/10.1016/S0887-2333(02)00002-4
  19. Louzao MC, Vieytes MR, Fontal O, Botana LM. 2003. Glucose uptake in enterocytes: a test for molecular targets of okadaic acid. J Recept Signal Transduct Res 23: 211-224. https://doi.org/10.1081/RRS-120025206
  20. Ball SW, Bailey JR, Stewart JM, Vogel CM, Westcott SA. 2002. A fluorescent compound for glucose uptake measurements in isolated rat cardiomyocytes. Can J Physiol Pharmacol 80: 205-209. https://doi.org/10.1139/y02-043
  21. Hanamura T, Mayama C, Aoki H, Hirayama Y, Shimizu M. 2006. Antihyperglycemic effect of polyphenols from Acerola (Malpighia emarginata DC.) fruit. Biosci Biotechnol Biochem 70: 1813-1820. https://doi.org/10.1271/bbb.50592
  22. Cermak R, Landgraf S, Wolffram S. 2004. Quercetin glucosides inhibit glucose uptake into brush-border-membrane vesicles of porcine jejunum. Br J Nutr 91: 849-855. https://doi.org/10.1079/BJN20041128
  23. Johnston K, Sharp P, Clifford M, Morgan L. 2005. Dietary polyphenols decrease glucose uptake by human intestinal Caco-2 cells. FEBS Lett 579: 1653-1657. https://doi.org/10.1016/j.febslet.2004.12.099
  24. Wagman AS, Nuss JM. 2001. Current therapies and emerging targets for the treatment of diabetes. Curr Pharm Des 7: 417-450. https://doi.org/10.2174/1381612013397915
  25. Yee HS, Fong NT. 1996. A review of the safety and efficacy of acarbose in diabetes mellitus. Pharmacotherapy 16: 792-805.
  26. Kim HK, Baek SS, Cho HY. 2011. Inhibitory effect of pomegranate on sodium dependent glucose uptake. Am J Chin Med In press.
  27. Oku A, Ueta K, Nawano M, Arakawa K, Kano-Ishihara T, Matsumoto M, Saito A, Tsujihara K, Anai M, Asano T. 2000. Antidiabetic effect of T-1095, an inhibitor of Na(+)-glucose cotransporter, in neonatally streptozotocintreated rats. Eur J Pharmacol 391: 183-192. https://doi.org/10.1016/S0014-2999(00)00016-9