Macroalgae of Izmir Gulf: Cystoseira barbata, Cystoseira compressa and Cystoseira crinita species have high α-glucosidase and Moderate Pancreatic Lipase Inhibition Activities

Document Type : Research article


1 Department of Medical Genetics, Faculty of Medicine, Ege University, Izmir, 35040, Turkey.

2 Department of Biology, Faculty of Science, Ege University, Izmir, 35040, Turkey.


 Hyperglycemia and hyperlipidemia have been symptoms of many serious diseases such as diabetes and atherosclerosis overall the world. Thus, drug researchers have focused on new, natural and healthy drug alternatives. Marine macroalgae is a great source of hypoglycemic, hypolipidemic or hypocholesterolemic agents. In this study, we investigated that hypoglycemic, hypolipidemic and cytotoxic potentials of 22 marine macroalgae from the Gulf of Izmir. According to our results, the cold methanol extract of Polysiphonia denudata exhibited the highest antioxidant activity (93.6%) compared to BHA (95.3%). Three Cystoseira species, Cystoseria crinita (91.9%), Cystoseria barbata (90.7%), Cystoseria compressa (89.8%) showed higher α-glucosidase inhibition rates than oral antidiabetic acarbose (79.5%). It has also been observed that same species are potent inhibitors of pancreatic lipase. Cytotoxicity test revealed that these extracts did not cause viability inhibition on MCF-7. The results of maltose- glucose assay indirectly displayed that Cystoseira cold methanolic extracts inhibited maltose consumption better than acarbose on HT29. The results of this screening study show that these Cystoseira species may provide non- toxic bioactive agents to control non-communicable diseases (NCDs) such as cardiovascular disease and diabetes mellitus.

Graphical Abstract

Macroalgae of Izmir Gulf: Cystoseira barbata, Cystoseira compressa and Cystoseira crinita species have high α-glucosidase and Moderate Pancreatic Lipase Inhibition Activities


Main Subjects

(1)         Association AD. 2. Classification and Diagnosis of Diabetes. Diabetes Care [serial online] 2017 January 40: S11 LP-S24. Available from: URL:
(2)         Saito N, Sakai H, Suzuki S, Sekihara H, and Yajima Y. Effect of an alpha-glucosidase inhibitor (voglibose), in combination with sulphonylureas, on glycaemic control in type 2 diabetes patients. J. Int. Med. Res. (1998) 26: 219–232.
(3)         Casirola DM and Ferraris RP. α-Glucosidase inhibitors prevent diet-induced increases in intestinal sugar transport in diabetic mice. Metabolism [serial online] 2006 55: 832–841. Available from: URL:
(4)         Charpentier G, Dardari D, and Riveline JP. How should postprandial glycemia be treated? Diabetes Metab. [serial online] 2006 32: 2S21-2S27. Available from: URL:
(5)         Giacco F and Brownlee M. Oxidative stress and diabetic complications. Circ. Res. (2010) 107: 1058–1070.
(6)         Wright EJ, Scism-Bacon JL, and Glass LC. Oxidative stress in type 2 diabetes: the role of fasting and postprandial glycaemia. Int. J. Clin. Pract. (2006) 60: 308–314.
(7)         Haffner SM. Pre-diabetes, insulin resistance, inflammation and CVD risk. Diabetes Res. Clin. Pract. (2003) 61 Suppl 1: S9–S18.
(8)         Piepoli MF, Hoes AW, Agewall S, Albus C, Brotons C, Catapano AL, et al. [2016 European guidelines on cardiovascular disease prevention in clinical practice. The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representat. G. Ital. Cardiol. (Rome). (2017) 18: 547–612.
(9)         Tucci SA, Boyland EJ, and Halford JC. The role of lipid and carbohydrate digestive enzyme inhibitors in the management  of obesity: a review of current and emerging therapeutic agents. Diabetes. Metab. Syndr. Obes. (2010) 3: 125–143.
(10)       Tonstad S, Pometta D, Erkelens DW, Ose L, Moccetti T, Schouten JA, et al. The effect of the gastrointestinal lipase inhibitor, orlistat, on serum lipids and lipoproteins in patients with primary hyperlipidaemia. Eur. J. Clin. Pharmacol. (1994) 46: 405–410.
(11)       Geng D, Jin D, Wu W, Fang C, and Wang J. Effect of alpha-glucosidase inhibitors on the progression of carotid intima-media thickness: A meta-analysis of randomized controlled trials. Atherosclerosis [serial online] 2011 218: 214–219. Available from: URL:
(12)       Folmer F, Jaspars M, Solano G, Cristofanon S, Henry E, Tabudravu J, et al. The inhibition of TNF-alpha-induced NF-kappaB activation by marine natural products. Biochem. Pharmacol. (2009) 78: 592–606.
(13)       Lee O-H, Yoon K-Y, Kim K-J, You S, and Lee B-Y. Seaweed extracts as a potential tool for the attenuation of the oxidative- related damage in obesity- related pathologies1. J. Phycol. (2011) 47: 548–556.
(14)       Wilson J, Hayes M, and Carney B. Angiotensin-I-converting enzyme and prolyl endopeptidase inhibitory peptides from natural sources with a focus on marine processing by-products. Food Chem. [serial online] 2011 129: 235–244. Available from: URL:
(15)       Abou-El-Wafa GSE, Shaaban M, Shaaban KA, El-Naggar MEE, Maier A, Fiebig HH, et al. Pachydictyols B and C: new diterpenes from Dictyota dichotoma Hudson. Mar. Drugs (2013) 11: 3109–3123.
(16)       Sangha J, Wally O, Banskota A, Stefanova R, Hafting J, Critchley A, et al. A Cultivated Form of a Red Seaweed (Chondrus crispus), Suppresses β-Amyloid-Induced Paralysis in Caenorhabditis elegans. Mar. Drugs [serial online] 2015 13: 6407–6424. Available from: URL:
(17)       Banskota AH, Stefanova R, Sperker S, Lall SP, Craigie JS, Hafting JT, et al. Polar lipids from the marine macroalga Palmaria palmata inhibit lipopolysaccharide-induced nitric oxide production in RAW264.7 macrophage cells. Phytochemistry [serial online] 2014 101: 101–108. Available from: URL:
(18)       Syad AN, Rajamohamed BS, Shunmugaiah KP, and Kasi PD. Neuroprotective effect of the marine macroalga Gelidiella acerosa: identification of active compounds through bioactivity-guided fractionation. Pharm. Biol. (2016) 54: 2073–2081.
(19)       Heo S-J, Hwang J-Y, Choi J-I, Han J-S, Kim H-J, and Jeon Y-J. Diphlorethohydroxycarmalol isolated from Ishige okamurae, a brown algae, a potent alpha-glucosidase and alpha-amylase inhibitor, alleviates postprandial hyperglycemia in diabetic mice. Eur. J. Pharmacol. (2009) 615: 252–256.
(20)       Lee S-H, Park M-H, Heo S-J, Kang S-M, Ko S-C, Han J-S, et al. Dieckol isolated from Ecklonia cava inhibits α-glucosidase and α-amylase in vitro and alleviates postprandial hyperglycemia in streptozotocin-induced diabetic mice. Food Chem. Toxicol. [serial online] 2010 48: 2633–2637. Available from: URL:
(21)       Nwosu F, Morris J, Lund VA, Stewart D, Ross HA, and McDougall GJ. Anti-proliferative and potential anti-diabetic effects of phenolic-rich extracts from edible marine algae. Food Chem. [serial online] 2011 126: 1006–1012. Available from: URL:
(22)       Lee S-H, Kang S-M, Ko S-C, Lee D-H, and Jeon Y-J. Octaphlorethol A, a novel phenolic compound isolated from a brown alga, Ishige foliacea, increases glucose transporter 4-mediated glucose uptake in skeletal muscle cells. Biochem. Biophys. Res. Commun. [serial online] 2012 420: 576–581. Available from: URL:
(23)       Min K-H, Kim H-J, Jeon Y-J, and Han J-S. Ishige okamurae ameliorates hyperglycemia and insulin resistance in C57BL/KsJ-db/db mice. Diabetes Res. Clin. Pract. [serial online] 2011 93: 70–76. Available from: URL:
(24)       Gómez-Ordóñez E, Jiménez-Escrig A, and Rupérez P. Effect of the red seaweed Mastocarpus stellatus intake on lipid metabolism and antioxidant status in healthy Wistar rats. Food Chem. [serial online] 2012 135: 806–811. Available from: URL:
(25)       Wilcox MD, Brownlee IA, Richardson JC, Dettmar PW, and Pearson JP. The modulation of pancreatic lipase activity by alginates. Food Chem. [serial online] 2014 146: 479–484. Available from: URL:
(26)       Shakambari G, Ashokkumar B, and Varalakshmi P. Phlorotannins from Brown Algae: inhibition of advanced glycation end products formation in high glucose induced Caenorhabditis elegans. Indian J. Exp. Biol. (2015) 53: 371–379.
(27)       Kim KY, Nam KA, Kurihara H, and Kim SM. Potent alpha-glucosidase inhibitors purified from the red alga Grateloupia elliptica. Phytochemistry (2008) 69: 2820–2825.
(28)       Lee S-H, Park M-H, Heo S-J, Kang S-M, Ko S-C, Han J-S, et al. Dieckol isolated from Ecklonia cava inhibits alpha-glucosidase and alpha-amylase  in vitro and alleviates postprandial hyperglycemia in streptozotocin-induced diabetic mice. Food Chem. Toxicol. (2010) 48: 2633–2637.
(29)       Park M-K, Jung U, and Roh C. Fucoidan from marine brown algae inhibits lipid accumulation. Mar. Drugs (2011) 9: 1359–1367.
(30)       Lordan S, Smyth TJ, Soler-Vila A, Stanton C, and Ross RP. The alpha-amylase and alpha-glucosidase inhibitory effects of Irish seaweed extracts. Food Chem. (2013) 141: 2170–2176.
(31)       Zhang LX, Zhang N, Li J, and Wang Z. New α-Glucosidase Inhibitory Polysaccharides Isolated from Marine Green Algae Enteromorpha Linza. Adv. Mater. Res. [serial online] 2013 January [cited 2017 Nov 5], 634–638: 1010–1015. Available from: URL:
(32)       Seo M-J, Lee O-H, Choi H-S, and Lee B-Y. Extract from Edible Red Seaweed (Gelidium amansii) Inhibits Lipid Accumulation and ROS Production during Differentiation in 3T3-L1 Cells. Prev. Nutr. food Sci. (2012) 17: 129–135.
(33)       Kim M-J and Kim HK. Insulinotrophic and hypolipidemic effects of Ecklonia cava in streptozotocin-induced diabetic mice. Asian Pac. J. Trop. Med. (2012) 5: 374–379.
(34)       Lee S-H, Min K-H, Han J-S, Lee D-H, Park D-B, Jung W-K, et al. Effects of brown alga, Ecklonia cava on glucose and lipid metabolism in C57BL/KsJ-db/db mice, a model of type 2 diabetes mellitus. Food Chem. Toxicol. (2012) 50: 575–582.
(35)       Zha X-Q, Xiao J-J, Zhang H-N, Wang J-H, Pan L-H, Yang X-F, et al. Polysaccharides in Laminaria japonica (LP): Extraction, physicochemical properties and their hypolipidemic activities in diet-induced mouse model of atherosclerosis. Food Chem. [serial online] 2012 134: 244–252. Available from: URL:
(36)       Lee C, Park GH, Ahn EM, Kim B-A, Park C-I, and Jang J-H. Protective effect of Codium fragile against UVB-induced pro-inflammatory and oxidative damages in HaCaT cells and BALB/c mice. Fitoterapia (2013) 86: 54–63.
(37)       Zhang W-W, Duan X-J, Huang H-L, Zhang Y, and Wang B-G. Evaluation of 28 marine algae from the Qingdao coast for antioxidative capacity and determination of antioxidant efficiency and total phenolic content of fractions and subfractions derived from Symphyocladia latiuscula (Rhodomelaceae). J. Appl. Phycol. [serial online] 2007 19: 97–108. Available from: URL:
(38)       Chiba S. Molecular mechanism in alpha-glucosidase and glucoamylase. Biosci. Biotechnol. Biochem. (1997) 61: 1233–1239.
(39)       Çelenk FG, Özkaya AB, and Sukatar A. Macroalgae of Izmir Gulf: Dictyotaceae exhibit high in vitro anti-cancer activity independent from their antioxidant capabilities. Cytotechnology [serial online] 2016 68: 2667–2676. Available from: URL:
(40)       De Rosa S et all. Chemical Composition and Biological Activities of the Black Sea Algae Polysiphonia denudata (Dillw.) Kutz. and Polysiphonia denudata f. fragilis (Sperk) Woronich. Vol. 56, Zeitschrift für Naturforschung C. (2001) 1008. Available from: URL:
(41)       Kamenarska Z, Serkedjieva J, Najdenski H, Stefanov K, Tsvetkova I, Dimitrova-Konaklieva S, et al. Antibacterial, antiviral, and cytotoxic activities of some red and brown seaweeds from the Black Sea. Bot. Mar. (2009) 52: 80–86.
(42)       De Rosa S, Kamenarska Z, Bankova V, Stefanov K, Dimitrova-Konaklieva S, Najdenski H, et al. Chemical composition and biological activities of the Black Sea algae Polysiphonia denudata (Dillw.) Kutz. and Polysiphonia denudata f. fragilis (Sperk) Woronich. Z. Naturforsch. C. (2001) 56: 1008–1014.
(43)       M.D. Guiry in Guiry, M.D. & Guiry GM. AlgBase. World-wide electronic publication, National University of Ireland, Galway. (2017). Available from: URL:
(44)       Fisch KM, Bohm V, Wright AD, and Konig GM. Antioxidative meroterpenoids from the brown alga Cystoseira crinita. J. Nat. Prod. (2003) 66: 968–975.
(45)       Guner A, Koksal C, Erel SB, Kayalar H, Nalbantsoy A, Sukatar A, et al. Antimicrobial and antioxidant activities with acute toxicity, cytotoxicity and mutagenicity of Cystoseira compressa (Esper) Gerloff & Nizamuddin from the coast of Urla (Izmir, Turkey). Cytotechnology (2015) 67: 135–143.
(46)       Sellimi S, Kadri N, Barragan-Montero V, Laouer H, Hajji M, and Nasri M. Fucans from a Tunisian brown seaweed Cystoseira barbata: Structural characteristics and antioxidant activity. Int. J. Biol. Macromol. [serial online] 2014 66: 281–288. Available from: URL:
(47)       Kosanic M, Rankovic B, and Stanojkovic T. Biological potential of marine macroalgae of the genus Cystoseira. Acta Biol. Hung. (2015) 66: 374–384.
(48)       Hadj Ammar H, Lajili S, Ben Said R, Le Cerf D, Bouraoui A, and Majdoub H. Physico-chemical characterization and pharmacological evaluation of sulfated polysaccharides from three species of Mediterranean brown algae of the genus Cystoseira. Daru (2015) 23: 1.
(49)       Mhadhebi L, Mhadhebi A, Robert J, and Bouraoui A. Antioxidant, Anti-inflammatory and Antiproliferative Effects of Aqueous Extracts  of Three Mediterranean Brown Seaweeds of the Genus Cystoseira. Iran. J. Pharm. Res.  IJPR (2014) 13: 207–220.
(50)       Zubia M, Fabre MS, Kerjean V, Lann K Le, Stiger-Pouvreau V, Fauchon M, et al. Antioxidant and antitumoural activities of some Phaeophyta from Brittany coasts. Food Chem. (2009) 116: 693–701.
(51)       Hetta M, Hassan S, Abdel-Tawab S, Bastawy M, and Mahmoud B. Hypolipidaemic effect of acanthophora spicifera (Red Alga) and cystoseira trinode (brown alga) on albino rats. Iran. J. Sci. Technol. Trans. A Sci. (2009) 33: 287–297.
(52)       Ben Gara A, Ben Abdallah Kolsi R, Jardak N, Chaaben R, El-Feki A, Fki L, et al. Inhibitory activities of Cystoseira crinita sulfated polysaccharide on key enzymes related to diabetes and hypertension: in vitro and animal study. Arch. Physiol. Biochem. [serial online] 2017 January [cited 2017 Sep 6], 123: 31–42. Available from: URL:
(53)       Nagy MA; Amin KA. Biochemical and histopathological analysis of Cystoseira myrica aqueous extract on alloxan induced diabetic rats. Biochem. An Indian J. (2015) 9: 81–91.
(54)       Hongayo MC. The Effect of Brown Alga Cystoseira Moniliformis ( Kützing ) Hauck Extract on the Blood Glucose Level of Alloxan-Induced Hyperglycemic Albino Mice ( Mus Musculus Linne , 1758 ). JPCS (2011) 3: 1–12.
(55)       Gulf P, Yegdaneh IA, Ghannadi A, Plubrukarn A, Zandi K, and Sartavi K. Acetylcholinesterase inhibitory activity of some seaweeds from. Res. Pharm. Sci. (2012) 7: 775.
(56)       Unnikrishnan PS, Suthindhiran K, and Jayasri MA. Alpha-amylase Inhibition and Antioxidant Activity of Marine Green Algae and its Possible Role in Diabetes Management. Pharmacogn. Mag. [serial online] 2015 October 11: S511–S515. Available from: URL:
(57)       Tas S, Celikler S, Ziyanok-Ayvalik S, Sarandol E, and Dirican M. Ulva rigida improves carbohydrate metabolism, hyperlipidemia and oxidative stress in streptozotocin-induced diabetic rats. Cell Biochem. Funct. (2011) 29: 108–113.