Journal of Applied Phycology

, Volume 31, Issue 5, pp 3143–3152 | Cite as

Phlorotannins from Fucales: potential to control hyperglycemia and diabetes-related vascular complications

  • Graciliana Lopes
  • Mariana Barbosa
  • Paula B. Andrade
  • Patrícia ValentãoEmail author


Key enzymes implicated in the metabolism of carbohydrates, such as the pancreatic α-amylase and the intestinal α-glucosidase, are the main targets of drugs designed to avoid and control hyperglycemia in diabetes mellitus. Phlorotannin-targeted extracts from four edible Fucus species, whose composition was previously established by mass spectrometry-based techniques (HPLC-DAD-ESI/MSn and UPLC-ESI-QTOF/MS), were able to inhibit both α-amylase and α-glucosidase carbohydrate-metabolizing enzymes, though being more effective towards the latter, with IC50 values significantly lower than those obtained for the pharmacological inhibitors acarbose and miglitol. The extracts also inhibited xanthine oxidase (XO), an enzymatic system usually overexpressed in diabetes and responsible for producing deleterious free radicals, such as superoxide anion radical (O2•-). Only Fucus guiryi and Fucus serratus extracts were able to scavenge O2•- under the tested concentrations. The biological potential displayed by the extracts was correlated with the total phlorotannin content. This is a pioneer study on the capacity of phlorotannin-targeted extracts from Fucus spp. to inhibit α-amylase, α-glucosidase, and XO, with special focus on enzyme kinetics, contributing for the valorization of the selected edible seaweeds and encouraging their incorporation in nutraceuticals and/or pharmaceuticals for glycemic control and to avoid the onset of diabetes-related vascular complications associated to oxidative stress.


Seaweeds Fucales Phlorotannins Diabetes α-Glucosidase α-Amylase Xanthine oxidase 


Funding information

This work received financial support from National Funds (FCT/MEC, Fundaçãopara a Ciência e Tecnologia/Ministério da Educação e Ciência) through project UID/QUI/50006/2013, co-financed by European Union (FEDER under the Partnership Agreement PT2020), from Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) (project NORTE-01-0145-FEDER-000024), and from Programa de Cooperación Interreg V-A España—Portugal (POCTEP) 2014-2020 (project 0377_IBERPHENOL_6_E). To all financing sources, the authors are greatly indebted. Mariana Barbosa (SFRH/BD/95861/2013) thanks FCT/MEC for the grant.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.


  1. Alberti KGMM, Zimmet PZ (1998) Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus. Provisional report of a WHO consultation. Diabet Med 15:539–553CrossRefPubMedGoogle Scholar
  2. Andrade PB, Barbosa M, Matos RP, Lopes G, Vinholes J, Mouga T, Valentão P (2013) Valuable compounds in macroalgae extracts. Food Chem 138:1819–1828CrossRefPubMedGoogle Scholar
  3. Balasubramaniam V, Lee JC, Noh MFM, Ahmad S, Brownlee IA, Ismail A (2016) Alpha-amylase, antioxidant, and anti-inflammatory activities of Eucheuma denticulatum (N.L. Burman) F.S. Collins and Hervey. J Appl Phycol 28:1965–1974CrossRefGoogle Scholar
  4. Barbosa M, Lopes G, Ferreres F, Andrade PB, Pereira DM, Gil-Izquierdo Á, Valentão P (2017) Phlorotannin extracts from Fucales: marine polyphenols as bioregulators engaged in inflammation-related mediators and enzymes. Algal Res 28:1–8CrossRefGoogle Scholar
  5. Chin YX, Lim PE, Maggs CA, Phang SM, Sharifuddin Y, Green BD (2015) Anti-diabetic potential of selected Malaysian seaweeds. J Appl Phycol 27:2137–2148CrossRefGoogle Scholar
  6. Desco MC, Asensi M, Márquez R, Martínez-Valls J, Vento M, Pallardó FV, Sastre J, Viña J (2002) Xanthine oxidase is involved in free radical production in type 1 diabetes: protection by allopurinol. Diabetes 51:1118–1124CrossRefPubMedGoogle Scholar
  7. Ferreres F, Lopes G, Gil-Izquierdo Á, Andrade PB, Sousa C, Mouga T, Valentão P (2012) Phlorotannin extracts from Fucales characterized by HPLC-DAD-ESI-MSn: approaches to hyaluronidase inhibitory capacity and antioxidant properties. Mar Drugs 10:2766–2781CrossRefPubMedPubMedCentralGoogle Scholar
  8. Fujisawa T, Ikegami H, Inoue K, Kawabata Y, Ogihara T (2005) Effect of two α-glucosidase inhibitors, voglibose and acarbose, on postprandial hyperglycemia correlates with subjective abdominal symptoms. Metabolism 54:387–390CrossRefPubMedGoogle Scholar
  9. Garret RH, Grisham CM (2017) Enzymes—kinetics and specificity. In: Garret RH, Grisham CM (eds) Biochemistry, 6th edn. Cengage Learning, Boston, pp 437–466Google Scholar
  10. Giacco F, Brownlee M (2010) Oxidative stress and diabetic complications. Circ Res 107:1058–1070CrossRefPubMedPubMedCentralGoogle Scholar
  11. Inkster ME, Cotter MA, Cameron NE (2007) Treatment with the xanthine oxidase inhibitor, allopurinol, improves nerve and vascular function in diabetic rats. Eur J Pharmacol 561:63–71CrossRefPubMedGoogle Scholar
  12. Jin DQ, Li G, Kim JS, Yong CS, Kim JA, Huh K (2004) Preventive effects of Laminaria japonica aqueous extract on the oxidative stress and xanthine oxidase activity in streptozotocin-induced diabetic rat liver. Biol Pharm Bull 27:1037–1040CrossRefPubMedGoogle Scholar
  13. Kellogg J, Grace MH, Lila MA (2014) Phlorotannins from Alaskan seaweed inhibit carbolytic enzyme activity. Mar Drugs 12:5277–5294CrossRefPubMedPubMedCentralGoogle Scholar
  14. Konya H, Katsuno T, Tsunoda T, Yano Y, Kamitani M, Miuchi M, Hamaguchi T, Miyagawa JI, Namba M (2013) Effects of combination therapy with mitiglinide and voglibose on postprandial plasma glucose in patients with type 2 diabetes mellitus. Diabetes Metab Syndr Obes 6:317–325CrossRefPubMedPubMedCentralGoogle Scholar
  15. Krentz AJ, Bailey CJ (2005) Oral antidiabetic agents. Drugs 65:385–411CrossRefPubMedGoogle Scholar
  16. Lebovitz HE (1997) Alpha-glucosidase inhibitors. Endocrinol Metab Clin N Am 26:539–551CrossRefGoogle Scholar
  17. Lebovitz HE (1998) α-Glucosidase inhibitors as agents in the treatment of diabetes. Diabetes Rev 6:132–145Google Scholar
  18. Li X, Meng X, Gao X, Pang X, Wang Y, Wu X, Deng X, Zhang Q, Sun C, Li Y (2018) Elevated serum xanthine oxidase activity is associated with the development of type 2 diabetes: a prospective cohort study. Diabetes Care 41:884–890PubMedGoogle Scholar
  19. Lopes G, Andrade PB, Valentão P (2016) Phlorotannins: towards new pharmacological interventions for diabetes mellitus type 2. Molecules 22:56CrossRefPubMedCentralGoogle Scholar
  20. Lopes G, Barbosa M, Vallejo F, Gil-Izquierdo Á, Andrade PB, Valentão P, Pereira DM, Ferreres F (2018) Profiling phlorotannins from Fucus spp. of the Northern Portuguese coastline: chemical approach by HPLC-DAD-ESI/MSn and UPLC-ESI-QTOF/MS. Algal Res 29:113–120CrossRefGoogle Scholar
  21. Lopes G, Sousa C, Silva LR, Pinto E, Andrade PB, Bernardo J, Mouga T, Valentão P (2012) Can phlorotannins purified extracts constitute a novel pharmacological alternative for microbial infections with associated inflammatory conditions? PLoS One 7:e31145CrossRefPubMedPubMedCentralGoogle Scholar
  22. Lordan S, Smyth TJ, Soler-Vila A, Stanton C, Ross RP (2013) The α-amylase and α-glucosidase inhibitory effects of Irish seaweed extracts. Food Chem 141:2170–2176CrossRefPubMedGoogle Scholar
  23. Maytin M, Leopold J, Loscalzo J (1999) Oxidant stress in the vasculature. Curr Atheroscler Rep 1:156–164CrossRefPubMedGoogle Scholar
  24. Miric DJ, Kisic BM, Filipovic-Danic S, Grbic R, Dragojevic I, Miric MB, Puhalo-Sladoje D (2016) Xanthine oxidase activity in type 2 diabetes mellitus patients with and without diabetic peripheral neuropathy. J Diabetes Res 2016:4370490CrossRefPubMedPubMedCentralGoogle Scholar
  25. Pacher P, Nivorozhkin A, Szabó C (2006) Therapeutic effects of xanthine oxidase inhibitors: renaissance half a century after the discovery of allopurinol. Pharmacol Rev 58:87–114CrossRefPubMedPubMedCentralGoogle Scholar
  26. Pantidos N, Boath A, Lund V, Conner S, McDougall GJ (2014) Phenolic-rich extracts from the edible seaweed, Ascophyllum nodosum, inhibit α-amylase and α-glucosidase: potential anti-hyperglycemic effects. J Funct Foods 10:201–209CrossRefGoogle Scholar
  27. Park SR, Kim JH, Jang HD, Yang SY, Kim YH (2018) Inhibitory activity of minor phlorotannins from Ecklonia cava on α-glucosidase. Food Chem 257:128–134CrossRefPubMedGoogle Scholar
  28. Pereira L (2009) Guia ilustrado das macroalgas: Conhecer e reconhecer algumas espécies da flora portuguesa. Imprensa da Universidade de Coimbra, CoimbraCrossRefGoogle Scholar
  29. Pirian K, Moein S, Sohrabipour J, Rabiei R, Blomster J (2017) Antidiabetic and antioxidant activities of brown and red macroalgae from the Persian Gulf. J Appl Phycol 29:3151–3159CrossRefGoogle Scholar
  30. Rajesh M, Mukhopadhyay P, Bátkai S, Mukhopadhyay B, Patel V, Haskó G, Szabó C, Mabley JG, Liaudet L, Pál Pacher P (2009) Xanthine oxidase inhibitor allopurinol attenuates the development of diabetic cardiomyopathy. J Cell Mol Med 13:2330–2341CrossRefPubMedGoogle Scholar
  31. Rasouli H, Hosseini-Ghazvini SM-B, Adibi H, Khodarahmi R (2017) Differential alpha-amylase/alpha-glucosidase inhibitory activities of plant-derived phenolic compounds: a virtual screening perspective for the treatment of obesity and diabetes. Food Funct 8:1942–1954CrossRefPubMedGoogle Scholar
  32. Rengasamy KRR, Aderogba MA, Amoo SO, Stirk WA, Van Staden J (2014) Macrocystis angustifolia is a potential source of enzyme inhibitors linked to type 2 diabetes and dementia. J Appl Phycol 26:1557–1563Google Scholar
  33. Stein SA, Lamos EM, Davis SN (2013) A review of the efficacy and safety of oral antidiabetic drugs. Expert Opin Drug Saf 12:153–175CrossRefPubMedGoogle Scholar
  34. Tatsumi F, Hashiramoto M, Hirukawa H, Kimura T, Shimoda M, Tawaramoto K, Kanda-Kimura Y, Anno T, Kawasaki F, Mune T, Matsuki M, Kaku K (2013) Concomitant use of miglitol and mitiglinide as initial combination therapy in type 2 diabetes mellitus. Diabetes Res Clin Pract 101:35–44CrossRefPubMedGoogle Scholar
  35. Unnikrishnan PS, Jayasri MA (2017) Antidiabetic studies of Chaetomorpha antennina extract using experimental models. J Appl Phycol 29:1047–1056CrossRefGoogle Scholar
  36. Urquiaga I, Leighton F (2000) Plant polyphenol antioxidants and oxidative stress. Biol Res 33:55–64CrossRefPubMedGoogle Scholar
  37. Valentão P, Fernandes E, Carvalho F, Andrade PB, Seabra RM, Bastos ML (2001) Antioxidant activity of Centaurium erythraea infusion evidenced by its superoxide radical scavenging and xanthine oxidase inhibitory activity. J Agric Food Chem 49:3476–3479CrossRefPubMedGoogle Scholar
  38. van de Laar FA (2008) Alpha-glucosidase inhibitors in the early treatment of type 2 diabetes. Vasc Health Risk Manag 4:1189–1195CrossRefPubMedPubMedCentralGoogle Scholar
  39. van de Laar FA, Lucassen PL, Akkermans RP, Van de Lisdonk EH, Rutten GE, Van Weel C (2005) Alpha-glucosidase inhibitors for type 2 diabetes mellitus. Cochrane Database Syst Rev 18:CD003639Google Scholar
  40. Wang T, Jónsdóttir R, Liu H, Gu L, Kristinsson HG, Raghavan S, Olafsdóttir G (2012) Antioxidant capacities of phlorotannins extracted from the brown algae Fucus vesiculosus. J Agric Food Chem 60:5874–5883CrossRefPubMedGoogle Scholar
  41. WHO (2016) Global report on diabetesGoogle Scholar
  42. Yousefi A, Yousefi R, Panahi F, Sarikhani S, Zolghadr AR, Bahaoddini A, Khalafi-Nezhad A (2015) Novel curcumin-based pyrano[2,3-d]pyrimidine anti-oxidant inhibitors for α-amylase and α-glucosidase: implications for their pleiotropic effects against diabetes complications. Int J Biol Macromol 78:46–55CrossRefPubMedGoogle Scholar
  43. Zardi GI, Nicastro KR, Canovas F, Ferreira Costa J, Serrão EA, Pearson GA (2011) Adaptive traits are maintained on steep selective gradients despite gene flow and hybridization in the intertidal zone. PLoS One 6:e19402CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.REQUIMTE/LAQV, Laboratório de Farmacognosia, Departamento de Química, Faculdade de FarmáciaUniversidade do PortoPortoPortugal

Personalised recommendations