Preferences help
enabled [disable] Abstract
Number of results
2011 | 58 | 1 | 45-50
Article title

Effects of olive leaf polyphenols against H2O2 toxicity in insulin secreting β-cells

Title variants
Languages of publication
In pancreatic β-cells, although H2O2 is a metabolic signal for glucose stimulated insulin secretion, it may induce injury in the presence of increased oxidative stress (OS) as in the case of diabetic chronic hyperglycemia. Olea europea L. (olive) leaves contain polyphenolic compounds that may protect insulin-secreting cells against OS. The major polyphenolic compound in ethanolic olive leaf extract (OLE) is oleuropein (about 20 %), thus we compared the effects of OLE with the effects of standard oleuropein on INS-1 cells. The cells were incubated with increasing concentrations of OLE or oleuropein for 24 h followed by exposure to H2O2 (0.035 mM) for 45 min. H2O2 alone resulted in a significantly decreased viability (MTT assay), depressed glucose-stimulated insulin secretion, increased apoptotic and necrotic cell death (AO/EB staining), inhibited glutathione peroxidase activity (GPx) and stimulated catalase activity that were associated with increased intracellular generation of reactive oxygen species (ROS) (fluorescence DCF). OLE and oleuropein partly improved the viability, attenuated necrotic and apoptotic death, inhibited the ROS generation and improved insulin secretion in H2O2-exposed cells. The effects of oleuropein on insulin secretion were more pronounced than those of OLE, while OLE exerted a stronger anti-cytotoxic effect than oleuropein. Unlike OLE, oleuropein had no significant preserving effect on GPx; however, both compounds stimulated the activity of catalase in H2O2-exposed cells. These findings indicate different modulatory roles of polyphenolic constituents of olive leaves on redox homeostasis that may have a role in the maintenance of β-cell physiology against OS.
Physical description
  • Gazi University, Faculty of Medicine, Department of Medical Biochemistry, Ankara, Turkey
  • Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, Bratislava, Slovak Republic
  • Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, Bratislava, Slovak Republic
  • Ankara University, Faculty of Pharmacy, Department of Pharmacognosy, Ankara, Turkey
  • Geneva University, Faculty of Medicine, Department of Cell Physiology and Metabolism, Geneva, Switzerland
  • Gazi University, Faculty of Medicine, Department of Medical Pharmacology, Ankara, Turkey.
  • Chandler D, Woldu A, Rahmadi A, Shanmugam K, Steiner N, Wright E, Benavente-García O, Schulz O, Castillo J, Münch G (2010) Effects of plant-derived polyphenols on TNF-alpha and nitric oxide production induced by advanced glycation endproducts. Mol Nutr Food Res 54 (Suppl 2): S141-S150.
  • Cnop M, Welsh N, Jonas JC, Jörns A, Lenzen S, Eizirik DL (2005) Mechanisms of pancreatic beta-cell death in type 1 and type 2 diabetes many differences, few similarities. Diabetes 54 (Suppl 2): S97-S107.
  • Covas MI (2007) Olive oil and the cardiovascular system. Pharmacol Res 55: 175-186.
  • Cvjetićanin T, Miljković D, Stojanović I, Dekanski D, Stosić-Grujicić S (2010) Dried leaf extract of Olea europaea ameliorates islet-directed autoimmunity in mice. Br J Nutr 103: 1413-1424.
  • Del Guerra S, Lupi R, Marselli L, Masini M, Bugliani M (2005) Functional and molecular defects of pancreatic islets in human type 2 diabetes. Diabetes 54: 727-735.
  • Eidi A, Eidi M, Darzi R (2009) Antidiabetic effect of Olea europaea L. in normal and diabetic rats. Phytother Res 23: 347-350.
  • Eizirik DL, Mandrup-Poulsen TA (2001) A choice of death - the signal-transduction of immune-mediated β-cell apoptosis. Diabetologia 44: 2115-2133.
  • Gariboldi P, Jommi G, Verotta L (1986) Secoiridoids from Olea europaea. Phytochemistry 25: 865-869.
  • Gembal M, Gilon P, Henquin JC (1992) Evidence that glucose can control insulin secretion independently from its action on ATP-sensitive K+channels in mouse B cells. J Clin Invest 89: 1288-1295.
  • Gonzalez M, Zarzuelo A, Gamez MJ, Utrilla MP, Jimenez J, Osuna I (1992) Hypoglycemic activity of olive leaf. Planta Medica 58: 513-515.
  • Gordon MH, Paiva-Martins F, Almeida M (2001) Antioxidant activity of hydroxytyrosol acetate compared with that of other olive oil polyphenols. J Agric Food Chem 49: 2480-2485.
  • Güneş A, Ceylan A, Sarioglu Y, Stefek M, Bauer V, Karasu C (2005) Antioxidants in Diabetes-induced Complications (ADIC) Study Group. Reactive oxygen species mediate abnormal contractile response to sympathetic nerve stimulation and noradrenaline in the vas deferens of chronically diabetic rats: effects of in vivo treatment with antioxidants. Fundam Clin Pharmacol 19: 73-79.
  • Hamden K, Allouche N, Damak M, Elfeki A (2009) Hypoglycemic and antioxidant effects of phenolic extracts and purified hydroxytyrosol from olive mill waste in vitro and in rats. Chem Biol Interact 180: 421-432.
  • Heimler D, Pieroni A, Tattini M, Cimato A (1992) Determination of flavonoids, flavonoid glycosides and biflavonoids in Olea europaea L. leaves. Chromatographia 33: 369-373.
  • Hervé-Grépinet V, Veillard F, Godat E, Heuzé-Vourc'h N, Lecaille F, Lalmanach G (2008) Extracellular catalase activity protects cysteine cathepsins from inactivation by hydrogen peroxide. FEBS Lett 582: 1307-1312.
  • Hou ZQ, Li HL, Zhao JJ, Li GW (2008) Impairment of pancreatic islet beta cell function induced by intermittent high glucose through oxidative and endoplasmic reticulum stress: experiment with rat pancreatic islet beta cells. Zhonghua Yi Xue Za Zhi 88: 2002-2004.
  • Ihara Y, Toyokuni S, Uchida K, Odaka H, Tanaka T, Ikeda H, Hiai H, Seino Y, Yamada Y (1999) Hyperglycemia causes oxidative stress in pancreatic beta-cells of GK rats, a model of type 2 diabetes. Diabetes 48: 927-932.
  • Janjic D, Wollheim CB (1992) Islet cell metabolism is reflected by the MTT (tetrazolium) colorimetric assay. Diabetologia 35: 482-485.
  • Jemai H, El Feki A, Sayadi S (2009) Antidiabetic and antioxidant effects of hydroxytyrosol and oleuropein from olive leaves in alloxan-diabetic rats. J Agric Food Chem 57: 8798-8804.
  • Kaneto H, Matsuoka TA, Katakami N, Kawamori D, Miyatsuka T, Yoshiuchi K, Yasuda T, Sakamoto K, Yamasaki Y, Matsuhisa M (2007) Oxidative stress and the JNK pathway are involved in the development of type 1 and type 2 diabetes. Curr Mol Med 7: 674-686.
  • Latha M, Pari L, Sitasawad S, Bhonde R (2004) Scoparia dulcis, a traditional antidiabetic plant, protects against streptozotocin induced oxidative stress and apoptosis in vitro and in vivo. J Biochem Mol Toxicol 18: 261-272.
  • Lin E, Wang Y, Mehendale S, Sun S, Wang CZ, Xie JT, Aung HH, Yuan CS (2008) Antioxidant protection by American ginseng in pancreatic beta-cells. Am J Chin Med 36: 981-988.
  • Maechler P, Jornot L, Wollheim CB (1999) Hydrogen peroxide alters mitochondrial activation and insulin secretion in pancreatic beta cells. J Biol Chem 274: 27905-27913.
  • Merglen A, Theander S, Rubi B, Chaffard G, Wollheim CB, Maechler P (2004) Glucose sensitivity and metabolism-secretion coupling studied during two-year continuous culture in INS-1E insulinoma cells. Endocrinology 145: 667-678.
  • Oliveras-López MJ, Berná G, Carneiro EM, López-García de la Serrana H, Martín F, López MC (2008) An extra-virgin olive oil rich in polyphenolic compounds has antioxidant effects in OF1 mice. J Nutr 138: 1074-1078.
  • Pi J, Bai Y, Zhang Q, Wong V, Floering LM, Daniel K, Reece JM, Deeney JT, Andersen ME, Corkey BE, Collins S (2007) Reactive oxygen species as a signal in glucose-stimulated insulin secretion. Diabetes 56: 1783-1791.
  • Raza H, John A (2005) Green tea polyphenol epigallocatechin-3-gallate differentially modulates oxidative stress in PC12 cell compartments. Toxicol Appl Pharmacol 207: 212-220.
  • Rhodes CJ (2005) Type 2 diabetes-a matter of beta-cell life and death? Science 307: 380-384.
  • Ribble D, Goldstein NB, Norris DA, Shellman YG (2005) A simple technique for quantifying apoptosis in 96-well plates. BMC Biotechnol 5: 12.
  • Robaszkiewicz A, Balcerczyk A, Bartosz G (2007) Antioxidative and prooxidative effects of quercetin on A549 cells. Cell Biol Int 31: 1245-1250.
  • Robertson R, Zhou H, Zhang T, Harmon JS (2007) Chronic oxidative stress as a mechanism for glucose toxicity of the beta cell in type 2 diabetes. Cell Biochem Biophys 48: 139-146.
  • Robertson RP, Harmon J, Tran PO, Tanaka Y, Takahashi h (2003) Glucose toxicity in beta-cells: type 2 diabetes, good radicals gone bad, and the glutathione connection. Diabetes 52: 581-587.
  • Robertson RP, Harmon JS (2006) Diabetes, glucose toxicity, and oxidative stress: A case of double jeopardy for the pancreatic islet beta cell. Free Radic Biol Med 41: 177-184.
  • Romani A, Baldi A, Tattini M, Vincieri FF (1994) Extraction, purification procedures and HPLC-RI analysis of carbohydrates in olive (Olea europaea L.) plants. Chromatographia 39: 35-39.
  • Rosenkranz AR, Schmaldienst S, Stuhlmeier KM, Chen W, Knapp W, Zlabinger GJ (1992) Microplate assay for the detection of oxidative products using 2',7'-dichlorofluorescein-diacetate. J Immunol Methods 156: 39-45.
  • Sakai K, Matsumoto K, Nishikawa T, Suefuji M, Nakamaru K, Hirashima Y, Kawashima J, Shirotani T, Ichinose K, Brownlee M, Araki E (2003) Mitochondrial reactive oxygen species reduce insulin secretion by pancreatic beta-cells. Biochem Biophys Res Commun 300: 216-222.
  • Sato H, Genet C, Strehle A, Thomas C, Lobstein A, Wagner A, Mioskowski C, Auwerx J, Saladin R (2007) Anti-hyperglycemic activity of a TGR5 agonist isolated from Olea europaea. Biochem Biophys Res Commun 362: 793-798.
  • Soni MG, Burdock GA, Christian MS, Bitler CM, Crea R (2006) Safety assessment of aqueous olive pulp extract as an antioxidant or antimicrobial agent in foods. Food Chem Toxicol 44: 903-915.
  • Speroni E, Guerra MC, Minghetti A Crespi-Perellino N, Pasini P, Piazza F (1998) Oleuropein evaluated in vitro and in vivo as an antioxidant. Phytother Res 12: 98-100.
  • Tanaka Y, Tran PO, Harmon J, Robertson RP (2002) A role for glutathione peroxidase in protecting pancreatic beta cells against oxidative stress in a model of glucose toxicity. Proc Natl Acad Sci USA 99: 12363-12368.
  • Visioli F, Bellomo G, Galli C (1998) Free radical scavenging properties of olive oil polyphenols. Biochem Biophys Res Commun 247: 60-64.
  • Xiong FL, Sun XH, Gan L, Yang XL, Xu HB (2006) Puerarin protects rat pancreatic islets from damage by hydrogen peroxide. Eur J Pharmacol 529: 1-7.
  • Yülek F, Or M, Ozoğul C, Isik AC, Ari N, Stefek M, Bauer V, Karasu C (2007) Effects of stobadine and vitamin E in diabetes-induced retinal abnormalities: involvement of oxidative stress. Arch Med Res 38: 503-511.
Document Type
Publication order reference
YADDA identifier
JavaScript is turned off in your web browser. Turn it on to take full advantage of this site, then refresh the page.