Abstract
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.
Similar content being viewed by others
References
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 15:539–553
Andrade PB, Barbosa M, Matos RP, Lopes G, Vinholes J, Mouga T, Valentão P (2013) Valuable compounds in macroalgae extracts. Food Chem 138:1819–1828
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 28:1965–1974
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 28:1–8
Chin YX, Lim PE, Maggs CA, Phang SM, Sharifuddin Y, Green BD (2015) Anti-diabetic potential of selected Malaysian seaweeds. J Appl Phycol 27:2137–2148
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 51:1118–1124
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 10:2766–2781
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 54:387–390
Garret RH, Grisham CM (2017) Enzymes—kinetics and specificity. In: Garret RH, Grisham CM (eds) Biochemistry, 6th edn. Cengage Learning, Boston, pp 437–466
Giacco F, Brownlee M (2010) Oxidative stress and diabetic complications. Circ Res 107:1058–1070
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 561:63–71
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 27:1037–1040
Kellogg J, Grace MH, Lila MA (2014) Phlorotannins from Alaskan seaweed inhibit carbolytic enzyme activity. Mar Drugs 12:5277–5294
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 6:317–325
Krentz AJ, Bailey CJ (2005) Oral antidiabetic agents. Drugs 65:385–411
Lebovitz HE (1997) Alpha-glucosidase inhibitors. Endocrinol Metab Clin N Am 26:539–551
Lebovitz HE (1998) α-Glucosidase inhibitors as agents in the treatment of diabetes. Diabetes Rev 6:132–145
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 41:884–890
Lopes G, Andrade PB, Valentão P (2016) Phlorotannins: towards new pharmacological interventions for diabetes mellitus type 2. Molecules 22:56
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 29:113–120
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:e31145
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 141:2170–2176
Maytin M, Leopold J, Loscalzo J (1999) Oxidant stress in the vasculature. Curr Atheroscler Rep 1:156–164
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 2016:4370490
Pacher P, Nivorozhkin A, Szabó C (2006) Therapeutic effects of xanthine oxidase inhibitors: renaissance half a century after the discovery of allopurinol. Pharmacol Rev 58:87–114
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 10:201–209
Park SR, Kim JH, Jang HD, Yang SY, Kim YH (2018) Inhibitory activity of minor phlorotannins from Ecklonia cava on α-glucosidase. Food Chem 257:128–134
Pereira L (2009) Guia ilustrado das macroalgas: Conhecer e reconhecer algumas espécies da flora portuguesa. Imprensa da Universidade de Coimbra, Coimbra
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 29:3151–3159
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 13:2330–2341
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 8:1942–1954
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 26:1557–1563
Stein SA, Lamos EM, Davis SN (2013) A review of the efficacy and safety of oral antidiabetic drugs. Expert Opin Drug Saf 12:153–175
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 101:35–44
Unnikrishnan PS, Jayasri MA (2017) Antidiabetic studies of Chaetomorpha antennina extract using experimental models. J Appl Phycol 29:1047–1056
Urquiaga I, Leighton F (2000) Plant polyphenol antioxidants and oxidative stress. Biol Res 33:55–64
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 49:3476–3479
van de Laar FA (2008) Alpha-glucosidase inhibitors in the early treatment of type 2 diabetes. Vasc Health Risk Manag 4:1189–1195
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:CD003639
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 60:5874–5883
WHO (2016) Global report on diabetes
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 78:46–55
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:e19402
Funding
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.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflicts of interest.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Lopes, G., Barbosa, M., Andrade, P.B. et al. Phlorotannins from Fucales: potential to control hyperglycemia and diabetes-related vascular complications. J Appl Phycol 31, 3143–3152 (2019). https://doi.org/10.1007/s10811-019-01816-7
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10811-019-01816-7