Zostera noltii extract lowers blood glucose and restores vascular function in diabetic rats

  • M. Zeki Haznedaroglu Ege University, Faculty of Pharmacy, Department of Pharmaceutical Botany 35100, Bornova, Izmir
  • Goksel Gokce Ege University, Faculty of Pharmacy, Department of Pharmacology 35100, Bornova, Izmir, Turkey
Keywords: Zostera noltii, Diabetes, Antioxidant, Phenolic compounds, Endothelial dysfunction


The antidiabetic effect of seagrass Zostera noltii extract was investigated through a crosstalk between its antioxidant and vasoprotective properties. The extract was orally administered to alloxan-diabetic rats (50, 150, 250 mg/kg body weight). Serum glucose was determined; liver and kidney functions, body weight, total leukocyte counts were measured; liver oxidative markers were assayed. Acetylcholine, phenylephrine and 5-HT responses were tested. eNOS levels and generation of ROS in aortic tissue were quantified. The extract of Z. noltii lowered blood glucose in all tested dose levels. Extract at a concentration of 50 mg/kg failed to preserve the levels of antioxidants and did not alter lipid peroxidation whereas higher doses improved liver oxidative status. Impaired acetylcholine relaxations, augmented phenylephrine and 5-HT contractions in alloxan-diabetic aortic rings were restored by Z. noltii treatment. This recovery was accompanied by increased eNOS synthesis and a reduction in ROS generation. The extract lowers blood glucose and prevents hyperglycemia-induced endothelial dysfunction in alloxan-diabetic rats.


Download data is not yet available.
706 Read

Author Biographies

M. Zeki Haznedaroglu, Ege University, Faculty of Pharmacy, Department of Pharmaceutical Botany 35100, Bornova, Izmir
Assistant Professor
Goksel Gokce, Ege University, Faculty of Pharmacy, Department of Pharmacology 35100, Bornova, Izmir, Turkey
Department of Pharmacology PhD Pharm. Researcher


Achamlale S, Rezzonico B, Grignon-Dubois M. Rosmarinic acid from beach waste: Isolation and HPLC quantification in Zostera detritus from Arcachon Lagoon. Food Chem. 2009; 113: 878-83.

Benter IF, Yousif MH, Canatan H, Akhtar S. Inhibition of Ca2+/calmodulin-dependent protein kinase II, RAS-GTPase and 20-hydroxyeicosatetraenoic acid attenuates the development of diabetes-induced vascular dysfunction in the rat carotid artery. Pharmacol Res. 2005; 52: 252-57.

Bergmeyer HW, Bernt E. Practical clinical biochemistry, In: Varley H, Gowenlock AH, Bell M. eds. London, England, William Heinemann Medicinal Books Ltd., 1980, p 741.

Brod J, Sirota JH. Practical clinical biochemistry, In: Varley H, Gowenlock AH, Bell M. (eds). London, England, William Heinemann Medicinal Books Ltd., 1948, p 190.

Chowienczyk PJ, Brett SE, Gopaul NK, Meeking D, Marchetti M, Russell-Jones DL, Anggard EE, Ritter JM. Oral treatment with an anti-oxidant (raxofelast) reduces oxidative stress and improves endothelial function in men with type II diabetes. Diabetologia 2000; 43: 974-77.

Cooperstein SJ, Walkins D. Action of toxic drugs on islet cells. In: The Islets of Langerhans. New York, USA, Academic Press, 1981, pp 387-90.

Cuny P, Serve L, Jupin H, Boudouresque CF. Water soluble phenolic compounds of the marine phanerogam Posidonia oceanica in a Mediterranean area colonised by the introduced chlorophyte Caulerpa taxifolia. Aquat Bot. 1995; 52: 237-42.

Fava D, Cassone-Faldetta M, Laurenti O, De Luca O, Ghiselli A, De Mattia G. Gliclazide improves anti-oxidant status and nitric oxide-mediated vasodilation in type 2 diabetes. Diabet Med. 2002; 19: 752-57.

Ferreira HC, Serra CP, Lemos VS, Braga FC, Cortes SF. Nitric oxide-dependent vasodilatation by ethanolic extract of Hancornia speciosa via phosphatidyl-inositol 3-kinase. J Ethnopharmacol. 2007; 109: 161-64.

Epstein FH. Glucose transporters and insulin action: Implica-tion for insulin resistance and diabetes mellitus. New Eng J Med. 1999; 341: 248-57.

Giugliano D, Ceriello A, Paolisso G. Oxidative stress and diabetic vascular complications. Diabetes Care. 1996; 19: 257-67.

Gokce G, Haznedaroglu MZ. Evaluation of antidiabetic, anti-oxidant and vasoprotective effects of Posidonia oceanica extract. J Ethnopharmacol. 2008; 115: 122-30.

Gong FY, Li FL, Zhang WM, Li JZhang Z. Effects of crude flavonoids from tatary buckwheat on alloxan-induced oxidative stress in mice. Bangladesh J Pharmacol. 2012; 7: 124-30.

Grignon-Dubois M, Rezzonico B, Alcoverro T. Regional scale patterns in seagrass defences: Phenolic acid content in Zostera noltii. Estuar Coast Shelf S. 2012; 114: 18-22.

Guevara I, Iwanejko J, Dembinska-Kiec A, Pankiewicz J, Wanat A, Anna P, Golabek I, Bartus S, Malczewska-Malec M, Szczudlik A. Determination of nitrite/nitrate in human biological material by the simple griess reaction. Clin Chim Acta. 1998; 274: 177-88.

Guo Z, Su W, Allen S, Pang H, Daugherty A, Smart E, Gong MC. Cox-2 up-regulation and vascular smooth muscle contractile hyperreactivity in spontaneous diabetic db/db mice. Cardiovasc Res. 2005; 67: 723-35.

Haklar G, Saybasili H, Yuksel M, Yalcin AS. Measurement of nitric oxide in hippocampal slices: Induction with nitroso compounds and the effect of depolarization. Acta Neurobiol Exp (Wars). 2003; 63: 319-25.

Haslam RH. Practical clinical biochemistry, In: Varley H, Gowenlock AH, Bell M. eds. London, England, William Heinemann Medicinal Books Ltd., 1966, p 459.

Karasu C. Time course of changes in endothelium-dependent and -independent relaxation of chronically diabetic aorta: Role of reactive oxygen species. Eur J Pharmacol. 2000; 392: 163-73.

Katusic ZS, Vanhoutte PM. Superoxide anion is an endothelium-derived contracting factor. Am J Physiol. 1989; 25: H33-H37.

King EJ, Armstrong AR. Practical clinical biochemistry, In: Varley H, Gowenlock AH, Bell M. eds. London, England, William Heinemann Medicinal Books Ltd., 1980, p 897.

Laight DW, Carrier MJ, Anggard EE. Endothelial cell dysfunction and the pathogenesis of diabetic macroangiopathy. Diabetes Metab Res Rev. 1999; 15: 274-82.

Lamaison JL, Petitjean-Freytet C, Carnat A. Rosmarinic acid, total hydroxycinnamic derivatives and anti-oxidant activity of Apiaceae, Boraginaceae and Lamiceae medicinals. Ann Pharm Fr. 1990; 48: 103-08.

Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the folin phenol reagent. J Biol Chem. 1951; 193: 265-75.

Meraji S, Jayakody L, Senaratne MP, Thomson AB, Kappagoda T. Endothelium-dependent relaxation in aorta of BB rat. Diabetes 1987; 36: 978-81.

Metz SA. Is phospholipase A2 a "Glucose sensor" responsible for the phasic pattern of insulin release? Prostaglandins 1984; 27: 147-58.

Mireia V, Angel B, Guillem C, Ibon G, Joxe Mikel G. Modelling suitable estuarine habitats for Zostera noltii, using ecological niche factor analysis and bathymetric lidar. Estuar Coast Shelf S. 2011; 94: 144-54.

Mohan DS, Saraswathy M, Kurup MKG. Attenuation of hyperglycemia and hyperlipidemia in high calorie fed/streptozotocin-treated rats by hydromethanolic extract of padina tetrastromatica. Bangladesh J Pharmacol. 2014; 9: 37-42.

Murugan P, Pari L. Anti-oxidant effect of tetrahydrocurcumin in streptozotocin-nicotinamide induced diabetic rats. Life Sci. 2006; 79: 1720-28.

Ndiaye M, Chataigneau M, Lobysheva I, Chataigneau T, Schini-Kerth VB. Red wine polyphenol-induced, endothelium-dependent nomediated relaxation is due to the redox-sensitive PI3-kinase/AKT-dependent phosphorylation of endothelial NO-synthase in the isolated porcine coronary artery. FASEB J. 2005; 19: 455-57.

Newberry RW, Ortega MJ, Zubia E, Romagni-Colvin JG. Seasonal variation in the phenolic secondary metabolites of Zostera noltii from the bay of Cadiz. 241st ACS National Meeting and Exposition, Anaheim, United States, 2011.

Oyama Y, Kawasaki H, Hattori Y, Kanno M. Attenuation of endothelium-dependent relaxation in aorta from diabetic rats. Eur J Pharmacol. 1986; 132: 75-78.

Papenbrock J. Highlights in Seagrasses’ Phylogeny, P, and Metabolism: What makes them special? ISRN Botany 2012; Article ID 103892 http://www.hindawi.com/journals/isrn.botany/2012/103892/.

Perfumi M, Tacconi R. Antihyperglycemic effect of fresh Opuntia dillenii fruit from Tenerife (Canary Islands). Pharm Biol. 1996; 34: 41-47.

Rao BK, Rao CH. Hypoglycemic and antihyperglycemic activity of Syzygium alternifolium (wt.) walp. seed extracts in normal and diabetic rats. Phytomedicine 2001; 8: 88-93.

Rehman A, Nourooz-Zadeh J, Moller W, Tritschler H, Pereira P, Halliwell B. Increased oxidative damage to all DNA bases in patients with type ii diabetes mellitus. FEBS Lett. 1999; 448: 120-22.

Rende F, Canese S, Rossi L, Izzi A, Nonnis O, Maggi C. Monitoring of seagrasses through underwater photographic images and video: Underwater pipelines case study. Mediterranean Seagrass Workshop, Essaouira, Morocco, 2012.

Sabu MC, Smitha K, Kuttan R. Anti-diabetic activity of green tea polyphenols and their role in reducing oxidative stress in experimental diabetes. J Ethnopharmacol. 2002; 83: 109-16.

Sakurai K, Katoh M, Someno K, Fujimoto Y. Apoptosis and mitochondrial damage in ins-1 cells treated with alloxan. Biol Pharm Bull. 2001; 24: 876-82.

Sato Y, Itagaki S, Kurokawa T, Ogura J, Kobayashi M, Hirano T, Sugawara M, Iseki K. In vitro and in vivo anti-oxidant properties of chlorogenic acid and caffeic acid. Int J Pharm. 2011; 403: 136-38.

Shukla N, Thompson CS, Angelini GD, Mikhailidis DP, Jeremy JY. Low micromolar concentrations of copper augment the impairment of endothelium-dependent relaxation of aortae from diabetic rabbits. Metabolism 2004; 53: 1315-21.

Signorini AM, Fondelli C, Renzoni E, Puccetti C, Gragnoli G, Giorgi G. Anti-oxidant effect of gliclazide, glibenclamide and metformin in patients with type 2 diabetes mellitus. Curr Ther Res Clin E. 2002; 63: 411-20.

Trinder P. Practical clinical biochemistry, In: Varley H, Gowenlock AH, Bell M. eds. London, England, William Heinemann Medicinal Books Ltd., 1976, p 389.

Walsh MF, Pek SB. Possible role of endogenous arachidonic acid metabolites in stimulated release of insulin and glucagon from the isolated, perfused rat pancreas. Diabetes 1984; 33: 929-36.

Wang HD, Xu S, Johns DG, Du Y, Quinn MT, Cayatte AJ, Cohen RA. Role of NADPH oxidase in the vascular hypertrophic and oxidative stress response to angiotensin II in mice. Circ Res. 2001; 88: 947-53.

Zeljan M, Misko P. Investigation of chemical composition of Zostera noltii Hornem. Farm Glas. 2000; 56: 109-18.

Zitouni K, Nourooz-Zadeh J, Harry D, Kerry SM, Betteridge DJ, Cappuccio FP, Earle KA. Race-specific differences in anti-oxidant enzyme activity in patients with type 2 diabetes: A potential association with the risk of developing nephropathy. Diabetes Care. 2005; 28: 1698-703.

How to Cite
Haznedaroglu, M. Z., and G. Gokce. “Zostera Noltii Extract Lowers Blood Glucose and Restores Vascular Function in Diabetic Rats”. Bangladesh Journal of Pharmacology, Vol. 9, no. 3, Aug. 2014, pp. 389-97, doi:10.3329/bjp.v9i3.19437.
Research Articles