Momordica charantia Protects against Cytokine-induced Apoptosis in Pancreatic $\beta$-Cells

  • Kim, Kyong (Food Function Research Center, Korea Food Research Institute) ;
  • Kim, Hye-Young (Food Function Research Center, Korea Food Research Institute)
  • 발행 : 2008.10.31

초록

The unripe fruit of Momordica charantia (MC) has been shown to possess antidiabetic activity. However, the mechanism of its antidiabetic action has not been fully understood. In this study, the effects of the aqueous ethanolic extract of MC (AEE-MC) were evaluated on the apoptosis in pancreatic $\beta$-cells treated with a combination of the cytokines, interleukin (IL)-$1{\beta}$, tumor necrosis factor (TNF)-$\alpha$, and interferon (IFN)-$\gamma$. In MIN6N8 cells, the inhibitory effect of AEE-MC was significantly observed at 2 to 50 ${\mu}g/mL$: a 26.2 to 55.6% decrease of cytoplasmic DNA fragments quantified by an immunoassay. The molecular mechanisms, by which AEE-MC inhibited $\beta$-cell apoptosis, appeared to involve the inhibition on the expression of p21, Bax, and Bad, the up-regulation of Bcl-2 and Bcl-$X_L$, and the inhibition on the cleavage of caspase-9, -7, and -3 and poly (ADP-ribose) polymerase. This study suggests that MC may inhibit cytokine-induced apoptosis in $\beta$-cells and, thus, may contribute via this action to the antidiabetic influence in diabetes.

키워드

참고문헌

  1. Sarkar S, Pranava M, Marita R. Demonstration of the hypoglycemic action of Momordica charantia in a validated animal model of diabetes. Pharmacol. Res. 33: 1-4 (1996) https://doi.org/10.1006/phrs.1996.0001
  2. Krawinkel MB, Keding GB. Bitter gourd (Momordica charantia): A dietary approach to hyperglycemia. Nutr. Rev. 64: 331-337 (2006) https://doi.org/10.1111/j.1753-4887.2006.tb00217.x
  3. Grover JK, Yadav SP. Pharmacological actions and potential uses of Momordica charantia: A review. J. Ethnopharmacol. 93: 123-132 (2004) https://doi.org/10.1016/j.jep.2004.03.035
  4. Basch E, Gabardi S, Ulbricht C. Bitter melon (Momordica charantia): A review of efficacy and safety. Am. J. Health Syst. Pharmacol. 60: 356-359 (2003)
  5. Raman A, Lau C. Anti-diabetic properties and phytochemistry of Momordica charantia L. (Cucurbitaceae). Phytomedicine 2: 349-362 (1996) https://doi.org/10.1016/S0944-7113(96)80080-8
  6. Shetty AK, Kumar S, Sambaiah K, Salimath PV. Effect of bitter gourd (Momordica charantia) on glycaemic status in streptozotocininduced diabetic rats. Plant. Food Hum. Nutr. 60: 109-112 (2005) https://doi.org/10.1007/s11130-005-6837-x
  7. Virdi J, Sivakami S, Shahani S, Suthar AC, Banavalikar MM, Biyani MK. Antihyperglycemic effects of three extracts from Momordica charantia. J. Ethnopharmacol. 88: 107-111 (2003) https://doi.org/10.1016/S0378-8741(03)00184-3
  8. Day C, Cartwright T, Provost J, Bailey CJ. Hypoglycemic effect of Momordica charantia extracts. Planta Med. 56: 426-429 (1990) https://doi.org/10.1055/s-2006-961003
  9. Akhtar MS, Athar MA, Yaqub M. Effect of on blood glucose level of normal and alloxan-diabetic rabbits. Planta Med. 42: 205-212 (1981) https://doi.org/10.1055/s-2007-971629
  10. Miura T, Itoh Y, Iwamoto N, Kato M, Ishida T. Suppressive activity of the fruit of Momordica charantia with exercise on blood glucose in type 2 diabetic mice. Biol. Pharm. Bull. 2: 248-250 (2004)
  11. Miura T, Itoh C, Iwamoto N, Kato M, Kawai M, Park SR, Suzuki I. Hypoglycemic activity of the fruit of the Momordica charantia in type 2 diabetic mice. J. Nutr. Sci. Vitaminol. 47: 340-344 (2001) https://doi.org/10.3177/jnsv.47.340
  12. Vikrant V, Grover JK, Tandon N, Rathi SS, Gupta N. Treatment with extracts of Momordica charantia and Eugenia jambolana prevents hyperglycemia and hyperinsulinemia in fructose fed rats. J. Ethnopharmacol. 76: 139-143 (2001) https://doi.org/10.1016/S0378-8741(01)00218-5
  13. Cnop M, Welsh N, Jonas JC, Jorns A, Lenzen S, Eizirik DL. Mechanisms of pancreatic ${\beta}-cell$ death in type 1 and type 2 diabetes. Diabetes 54: S97-S107 (2005) https://doi.org/10.2337/diabetes.54.suppl_2.S97
  14. Rhodes CJ. Type 2 diabetes - a matter of ${\beta}-cell$ life and death? Science 307: 380-384 (2005) https://doi.org/10.1126/science.1104345
  15. Mathis D, Vence L, Benoist C. ${\beta}-cell$ death during progression to diabetes. Nature 414: 792-798 (2001) https://doi.org/10.1038/414792a
  16. Wang K, Yin X-M, Cao DT, Milliman CL, Korsmeyer SJ. BID: A novel BH3 domain-only death agonist. Gene Dev. 10: 2859-2869 (1996) https://doi.org/10.1101/gad.10.22.2859
  17. Oltvai ZN, Milliman CL, Korsmeyer SJ. Bcl-2 heterodimerizes in vivo with a conserved homolog, bax that accelerates programmed cell death. Cell 74: 609-619 (1993) https://doi.org/10.1016/0092-8674(93)90509-O
  18. Zou H, Henzel WJ, Liu X, Lutschg A, Wang X. Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of caspase-3. Cell 90: 405-413 (1997) https://doi.org/10.1016/S0092-8674(00)80501-2
  19. Li P, Nijhawan D, Budihardjo I, Srinivasula SM, Ahmad M, Alnemri ES, Wang X. Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell 91: 479-489 (1997) https://doi.org/10.1016/S0092-8674(00)80434-1
  20. Sitasawad SL, Shewade Y, Bhonde R. Role of bittergourd fruit juice in stz-induced diabetic state in vivo and in vitro. J. Ethnopharmacol. 73: 71-79 (2000) https://doi.org/10.1016/S0378-8741(00)00282-8
  21. Yagi N, Yokono K, Amano K, Nagata M, Tsukamoto K, Hasegawa Y, Yoneda R, Okamoto N, Moriyama H, Miki M, Tominaga Y, Miyazaki JI, Yagita H, Okumura K, Mizoguchi A, Miki A, Ide C, Maeda S, Kasuga M. Expression of intercellular adhesion molecule 1 on pancreatic ${\beta}-cell$ destruction by cytotoxic T-cells in murine autoimmune diabetes. Diabetes 44: 744-752 (1995) https://doi.org/10.2337/diabetes.44.7.744
  22. Di Matteo MA, Loweth AC, Thomas S, Mabley JG, Morgan NG, Thorpe JR, Green IC. Superoxide, nitric oxide, peroxynitrite, and cytokine combinations all cause functional impairment and morphological changes in rat islets of langerhans and insulinsecreting cell lines but dictate cell death by different mechanism. Apoptosis 2: 164-177 (1997) https://doi.org/10.1023/A:1026412414666
  23. Kumar R, Mandal M, Lipton A, Harvey H, Thompson CB. Overexpression of HER2 modulates Bcl-2, $Bcl-X_L$, and tamoxifeninduced apoptosis in human MCF-7 breast cancer cells. Clin. Cancer Res. 2: 1215-1219 (1996)
  24. Kim HY, Kim K. Protective effect of ginseng on cytokine-induced apoptosis in pancreatic ${\beta}-cells$. J. Agr. Food Chem. 55: 2816-2823 (2007) https://doi.org/10.1021/jf062577r
  25. Allen RT, Hunter WJ III, Agrawal DW. Morphological and biochemical characterization and analysis of apoptosis. J. Pharmacol. Toxicol. 37: 215-228 (1997) https://doi.org/10.1016/S1056-8719(97)00033-6
  26. Hui H, Nourparvar A, Zhao X, Perfetti R. Glucagon-like peptide-1 inhibits apoptosis of insulin-secreting cells via a cyclic 5'-adenosine monophosphate-dependent protein kinase A- and a phosphatidylinositol kinase-dependent pathway. Endocrinology 144: 1444-1455 (2003) https://doi.org/10.1210/en.2002-220897
  27. Tewari M, Quan LT, O'Rourke K, Desnoyers S, Zeng Z, Beidler DR, Poirier GG, Salvessen GS, Dixit VM. $Yama/CPP32{\beta}$, a mammalian homology of CED-3, is a CrmA-inhibitable protease that cleaves the death substrate poly(ADP-ribose) polymerase. Cell 81: 801-809 (1995) https://doi.org/10.1016/0092-8674(95)90541-3
  28. Sansome C, Zaika A, Marchenko ND, Moll UT. Hypoxia death stimulus induces translocation of p53 protein to mitochondria. FEBS Lett. 488: 110-115 (2001) https://doi.org/10.1016/S0014-5793(00)02368-1
  29. Donath MY, Gross DJ, Cerasi E, Kaiser N. Hyperglycemia-induced ${\beta}-cell$ apoptosis in pancreatic islets of Psammomys obesus during development of diabetes. Diabetes 48: 738-744 (1999) https://doi.org/10.2337/diabetes.48.4.738
  30. Li P-F, Dietz R, Harsdorf R. p53 regulates mitochondrial membrane potential through reactive oxygen species and induces cytochrome c-independent apoptosis blocked by Bcl-2. EMBO J. 18: 6027-6036 (1999) https://doi.org/10.1093/emboj/18.21.6027