Skip to main content
Log in

Low molecular weight fucoidan ameliorates the inflammation and glomerular filtration function of diabetic nephropathy

  • Published:
Journal of Applied Phycology Aims and scope Submit manuscript

Abstract

Diabetic nephropathy (DN) is a type of serious microangiopathy that is caused by diabetes mellitus (DM). It is the most common cause of chronic renal failure and end-stage renal disease, and it severely affects patients’ quality of life. This work aims to study the effect and mechanism of low molecular weight fucoidan (LMWF) on streptozotocin (STZ)-induced DN. The experimental results showed that LMWF prevented weight loss in DN rats, significantly reduced the levels of biochemical indexes in blood and urine samples, and also lowered hyaluronic acid (HA) levels and advanced glycosylation end product-specific receptor (AGER) levels in DN rats. LMWF maintained the structural integrity of glomerular basement membrane (GBM) and glomerulus, improved the glomerular filtration function, protected glycosaminoglycan from abnormal degrading, prevented advanced glycosylation end product (AGE) from being generated and accumulating, and also alleviated inflammatory response in DN rats. LMWF could obviously ameliorate and slow the development and progression of DN in rats.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11

Similar content being viewed by others

References

  • Anastyuk SD, Shevchenko NM, Ermakova SP, Vishchuk OS, Nazarenko EL, Dmitrenok PS, Zvyagintseva TN (2012) Anticancer activity in vitro of a fucoidan from the brown alga Fucus evanescens and its low-molecular fragments, structurally characterized by tandem mass-spectrometry. Carbohydr Polym 87:186–194

    Article  CAS  Google Scholar 

  • Bachelet L, Bertholon I, Lavigne D, Vassy R, Jandrot-Perrus M, Chaubet F, Letourneur D (2009) Affinity of low molecular weight fucoidan for P-selectin triggers its binding to activated human platelets. Biochim Biophys Acta 1790:141–146

    Article  CAS  PubMed  Google Scholar 

  • Bishop JR, Schuksz M, Esko JD (2007) Heparan sulphate proteoglycans fine-tune mammalian physiology. Nature 446:1030–1037

    Article  CAS  PubMed  Google Scholar 

  • Burns WC, Twigg SM, Forbes JM, Pete J, Tikellis C, Thallas-Bonke V, Thomas MC, Cooper ME, Kantharidis P (2006) Connective tissue growth factor plays an important role in advanced glycation end product-induced tubular epithelial-to-mesenchymal transition: implications for diabetic renal disease. J Am Soc Nephrol 17:2484–2494

    Article  CAS  PubMed  Google Scholar 

  • Chen J, Wang W, Zhang Q, Li F, Lei T, Luo D, Zhou H, Yang B (2013) Low molecular weight fucoidan against renal ischemia-reperfusion injury via inhibition of the MAPK signaling pathway. PLoS One 8:e56224

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Conde-Knape K (2001) Heparan sulfate proteoglycans in experimental models of diabetes: a role for perlecan in diabetes complications. Diabetes Metab Res Rev 17:412–421

    Article  CAS  PubMed  Google Scholar 

  • Costa LS, Fidelis GP, Cordeiro SL, Oliveira RM, Sabry DA, Camara RB, Nobre LT, Costa MS, Almeida-Lima J, Farias EH, Leite EL, Rocha HA (2010) Biological activities of sulfated polysaccharides from tropical seaweeds. Biomed Pharmacother 64:21–28

    Article  CAS  PubMed  Google Scholar 

  • Cui W, Zheng Y, Zhang Q, Wang J, Wang L, Yang W, Guo C, Gao W, Wang X, Luo D (2014) Low-molecular-weight fucoidan protects endothelial function and ameliorates basal hypertension in diabetic Goto-Kakizaki rats. Lab Investig 94:382–393

    Article  CAS  PubMed  Google Scholar 

  • Deux JF, Meddahi-Pellé A, Le Blanche AF, Feldman LJ, Colliec-Jouault S, Brée F, Boudghène F, Michel JB, Letourneur D (2002) Low molecular weight fucoidan prevents neointimal hyperplasia in rabbit iliac artery in-stent restenosis model. Arterioscler Thromb Vasc Biol 22:1604–1609

    Article  CAS  PubMed  Google Scholar 

  • Durand E, Helley D, Al Haj Zen A, Dujols C, Bruneval P, Colliec-Jouault S, Fischer AM, Lafont A (2008) Effect of low molecular weight fucoidan and low molecular weight heparin in a rabbit model of arterial thrombosis. J Vasc Res 45:529–537

    Article  CAS  PubMed  Google Scholar 

  • Durig J, Bruhn T, Zurborn K, Gutensohn K, Bruhn H, Beress L (1997) Anticoagulant fucoidan fractions from Fucus vesiculosus induce platelet activation in vitro. Thromb Res 85:479–491

    Article  CAS  PubMed  Google Scholar 

  • Fan WX, Deng ZX, Liu F, Liu RB, He L, Amrit B, Zang L, Li JW, Liu XR, Huang SM, et al. (2012) Spontaneous retroperitoneal hemorrhage after hemodialysis involving anticoagulant agents. J Zhejiang Univ Sci B 13:408–412

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Group IDFDA (2015)) Update of mortality attributable to diabetes for the IDF Diabetes Atlas: estimates for the year 2013. In Diabetes Res Clin Pract 109:461–465

    Article  Google Scholar 

  • Haraldsson B, Nystrom J, Deen W (2008) Properties of the glomerular barrier and mechanisms of proteinuria. Physiol Rev 88:451–487

    Article  CAS  PubMed  Google Scholar 

  • Hemmingson JA, Falshaw R, Furneaux RH, Thompson K (2006) Structure and antiviral activity of the galactofucan sulfates extracted from Undaria pinnatifida (Phaeophyta). J Appl Phycol 18:185–193

    Article  CAS  Google Scholar 

  • Hlawaty H, Suffee N, Sutton A, Oudar O, Haddad O, Ollivier V, Laguillier-Morizot C, Gattegno L, Letourneur D, Charnaux N (2011) Low molecular weight fucoidan prevents intimal hyperplasia in rat injured thoracic aorta through the modulation of matrix metalloproteinase-2 expression. Biochem Pharmacol 81:233–243

    Article  CAS  PubMed  Google Scholar 

  • Iozzo R, Pillarisetti J, Sharma B, Murdoch AD, Danielson KG, Uitto J, Mauviel A (1997) Structural and functional characterization of the human perlecan gene promoter. Transcriptional activation by transforming growth factor-beta via a nuclear factor 1-binding element. J Biol Chem 272:5219–5228

    Article  CAS  PubMed  Google Scholar 

  • Jiao G, Yu G, Zhang J, Ewart HS (2011) Chemical structures and bioactivities of sulfated polysaccharides from marine algae. Mar Drugs 9:196–223

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jin W, Wang J, Jiang H, Song N, Zhang W, Zhang Q (2013) The neuroprotective activities of heteropolysaccharides extracted from Saccharina japonica. Carbohydr Polym 97:116–120

    Article  CAS  PubMed  Google Scholar 

  • Li J, Qu X, Yao J, Caruana G, Ricardo SD, Yamamoto Y, Yamamoto H, Bertram JF (2010) Blockade of endothelial-mesenchymal transition by a Smad3 inhibitor delays the early development of streptozotocin-induced diabetic nephropathy. Diabetes 59:2612–2624

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kanasaki K, Taduri G, Koya D (2013) Diabetic nephropathy: the role of inflammation in fibroblast activation and kidney fibrosis. Front Endocrinol 4:7

    Article  Google Scholar 

  • Kanwar YS, Sun L, Xie P, Liu FY, Chen S (2011) A glimpse of various pathogenetic mechanisms of diabetic nephropathy. Annu Rev Pathol 6:395–423

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kashihara N, Haruna Y, Kondeti VK, Kanwar YS (2010) Oxidative stress in diabetic nephropathy. Curr Med Chem 17:4256–4269

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lim AK, Tesch GH (2012) Inflammation in diabetic nephropathy. Mediat Inflamm 2012:146154

    Article  Google Scholar 

  • Ma J, Wu H, Zhao CY, Panchapakesan U, Pollock C, Chadban SJ (2014) Requirement for TLR2 in the development of albuminuria, inflammation and fibrosis in experimental diabetic nephropathy. Int J Clin Exp Pathol 7:481–495

    CAS  PubMed  PubMed Central  Google Scholar 

  • Matsushita Y, Ogawa D, Wada J, Yamamoto N, Shikata K, Sato C, Tachibana H, Toyota N, Makino H (2011) Activation of peroxisome proliferator-activated receptor delta inhibits streptozotocin-induced diabetic nephropathy through anti-inflammatory mechanisms in mice. Diabetes 60:960–968

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McCarthy KJ, Wassenhove-McCarthy DJ (2012) The glomerular basement membrane as a model system to study the bioactivity of heparan sulfate glycosaminoglycans. Microsc Microanal 18:3–21

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nardella A, Chaubet F, BoissonVidal C, Blondin C, Durand P, Jozefonvicz J (1996) Anticoagulant low molecular weight fucans produced by radical process and ion exchange chromatography of high molecular weight fucans extracted from the brown seaweed Ascophyllum nodosum. Carbohydr Res 289:201–208

    Article  CAS  PubMed  Google Scholar 

  • Naylor RN, Greeley SA, Bell GI, Philipson LH (2011) Genetics and pathophysiology of neonatal diabetes mellitus. J Diabetes Investig 2:158–169

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nazir K, Siddiqui K, Al-Qasim S, Al-Naqeb D (2014) Meta-analysis of diabetic nephropathy associated genetic variants in inflammation and angiogenesis involved in different biochemical pathways. BMC Med Genet 15:103

    Article  PubMed  PubMed Central  Google Scholar 

  • Pal PB, Sinha K, Sil PC (2014) Mangiferin attenuates diabetic nephropathy by inhibiting oxidative stress mediated signaling cascade, TNFalpha related and mitochondrial dependent apoptotic pathways in streptozotocin-induced diabetic rats. PLoS One 9:e107220

    Article  PubMed  PubMed Central  Google Scholar 

  • Pan Y, Huang Y, Wang Z, Fang Q, Sun Y, Tong C, Peng K, Wang Y, Miao L, Cai L, Zhao Y, Liang G (2014) Inhibition of MAPK-mediated ACE expression by compound C66 prevents STZ-induced diabetic nephropathy. J Cell Mol Med 18:231–241

    Article  CAS  PubMed  Google Scholar 

  • Papale M, Papale M, Di Paolo S, Magistroni R, Lamacchia O, Di Palma AM, De Mattia A, Rocchetti MT, Furci L, Pasquali S, De Cosmo S, Cignarelli M, Gesualdo L (2010) Urine proteome analysis may allow noninvasive differential diagnosis of diabetic nephropathy. Diabetes Care 33:2409–2415

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Remuzzi G, Schieppati A, Ruggenenti P (2002) Nephropathy in patients with type 2 diabetes. N Engl J Med 346:1145–1151

    Article  PubMed  Google Scholar 

  • Rossini M, Naito T, Yang H, Freeman M, Donnert E, Ma LJ, Dunn SR, Sharma K, Fogo AB (2010) Sulodexide ameliorates early but not late kidney disease in models of radiation nephropathy and diabetic nephropathy. Nephrol Dial Transplant 25:1803–1810

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sakagami Y, Nakajima M, Takagawa K, Ueda T, Akazawa H, Maruhashi Y, Shimoyama H, Kamitsuji H, Yoshioka A (2004) Analysis of glomerular anionic charge status in children with IgA nephropathy using confocal laser scanning microscopy. Nephron Clin Pract 96:c96–c104

    Article  CAS  PubMed  Google Scholar 

  • Satchell SC, Braet F (2009) Glomerular endothelial cell fenestrations: an integral component of the glomerular filtration barrier. Am J Physiol Renal Physiol 296:F947–F956

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sawa Y, Takata S, Hatakeyama Y, Ishikawa H, Tsuruga E (2014) Expression of toll-like receptor 2 in glomerular endothelial cells and promotion of diabetic nephropathy by Porphyromonas gingivalis lipopolysaccharide. PLoS One 9:e0097165

    Article  Google Scholar 

  • Singh A, Satchell SC, Neal CR, McKenzie EA, Tooke JE, Mathieson PW (2007) Glomerular endothelial glycocalyx constitutes a barrier to protein permeability. J Am Soc Nephrol 18:2885–2893

    Article  CAS  PubMed  Google Scholar 

  • Singh VP, Bali A, Singh N, Jaggi AS (2014) Advanced glycation end products and diabetic complications. Korean J Physiol Pharmacol 18:1–14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Takahashi S, Watanabe S, Wada N, Murakami H, Funaki S, Yan K, Kondo Y, Harada K, Nagata M (2006) Charge selective function in childhood glomerular diseases. Pediatr Res 59:336–340

    Article  PubMed  Google Scholar 

  • Terami N, Ogawa D, Tachibana H, Hatanaka T, Wada J, Nakatsuka A, Eguchi J, Horiguchi CS, Nishii N, Yamada H, Takei K, Makino H (2014) Long-term treatment with the sodium glucose cotransporter 2 inhibitor, dapagliflozin, ameliorates glucose homeostasis and diabetic nephropathy in db/db mice. PLoS One 9:e100777

    Article  PubMed  PubMed Central  Google Scholar 

  • Tomita H, Sanford RB, Smithies O, Kakoki M (2012) The kallikrein-kinin system in diabetic nephropathy. Kidney Int 81:733–744

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vlassara H, Striker GE (2011) AGE restriction in diabetes mellitus: a paradigm shift. Nat Rev Endocrinol 7:526–539

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang CZ, Ho ML, Chen WC, Chiu CC, Hung YL, Wang CK, Wu SC (2011a) Characterization and enhancement of chondrogenesis in porous hyaluronic acid-modified scaffolds made of PLGA(75/25) blended with PEI-grafted PLGA(50/50). Mar Sci Eng C 31:1343–1351

    Article  CAS  Google Scholar 

  • Wang J, Liu H, Li N, Zhang Q, Zhang H (2014) The protective effect of fucoidan in rats with streptozotocin-induced diabetic nephropathy. Mar Drugs 12:3292–3306

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang J, Wang F, Yun H, Zhang H, Zhang Q (2012) Effect and mechanism of fucoidan derivatives from Laminaria japonica in experimental adenine-induced chronic kidney disease. J Ethnopharmacol 139:807–813

    Article  CAS  PubMed  Google Scholar 

  • Wang J, Zhang Q, Jin W, Niu X, Zhang H (2011b) Effects and mechanism of low molecular weight fucoidan in mitigating the peroxidative and renal damage induced by adenine. Carbohydr Polym 84:417–423

    Article  CAS  Google Scholar 

  • Wang J, Zhang Q, Zhang Z, Li Z (2008) Antioxidant activity of sulfated polysaccharide fractions extracted from Laminaria japonica. Int J Biol Macromol 42:127–132

    Article  PubMed  Google Scholar 

  • Wang J, Zhang Q, Zhang Z, Song H, Li P (2010a) Potential antioxidant and anticoagulant capacity of low molecular weight fucoidan fractions extracted from Laminaria japonica. Int J Biol Macromol 46:6–12

    Article  CAS  PubMed  Google Scholar 

  • Wang J, Zhang Q, Zhang Z, Zhang H, Niu X (2010b) Structural studies on a novel fucogalactan sulfate extracted from the brown seaweed Laminaria japonica. Int J Biol Macromol 47:126–131

    Article  CAS  PubMed  Google Scholar 

  • Weil EJ, Lemley KV, Mason CC, Yee B, Jones LI, Blouch K, Lovato T, Richardson M, Myers BD, Nelson RG (2012) Podocyte detachment and reduced glomerular capillary endothelial fenestration promote kidney disease in type 2 diabetic nephropathy. Kidney Int 82:1010–1017

    Article  PubMed  PubMed Central  Google Scholar 

  • Wendt TM, Tanji N, Guo J, Kislinger TR, Qu W, Lu Y, Bucciarelli LG, Rong LL, Moser B, Markowitz GS, Stein G, Bierhaus A, Liliensiek B, Arnold B, Nawroth PP, Stern DM, D'Agati VD, Schmidt AM (2003) RAGE drives the development of glomerulosclerosis and implicates podocyte activation in the pathogenesis of diabetic nephropathy. Am J Pathol 162:1123–1137

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wijesekara I, Pangestuti R, Kim SK (2011) Biological activities and potential health benefits of sulfated polysaccharides derived from marine algae. Carbohydr Polym 84:14–21

    Article  CAS  Google Scholar 

  • Yamagishi S, Matsui T (2010) Advanced glycation end products, oxidative stress and diabetic nephropathy. Oxidative Med Cell Longev 3:101–108

    Article  Google Scholar 

  • Yu X, Zhang Q, Cui W, Zeng Z, Yang W, Zhang C, Zhao H, Gao W, Wang X, Luo D (2014) Low molecular weight fucoidan alleviates cardiac dysfunction in diabetic Goto-Kakizaki rats by reducing oxidative stress and cardiomyocyte apoptosis. J Diabetes Res 2014:420929

    Article  PubMed  PubMed Central  Google Scholar 

  • Yung S, Chau M, Zhang Q, Zhang C, Chan T (2013) Sulodexide decreases albuminuria and regulates matrix protein accumulation in C57BL/6 mice with streptozotocin-induced type I diabetic nephropathy. PLoS One 8:e54501

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang MZ, Wang S, Yang S, Yang H, Fan X, Takahashi T, Harris RC (2012) Role of blood pressure and the renin-angiotensin system in development of diabetic nephropathy (DN) in eNOS-/- db/db mice. Am J Physiol Renal Physiol 302:F433–F438

    Article  CAS  PubMed  Google Scholar 

  • Zhang Z, Teruya K, Eto H, Shirahata S (2013) Induction of apoptosis by low-molecular-weight fucoidan through calcium- and caspase-dependent mitochondrial pathways in MDA-MB-231 breast cancer cells. Biosci Biotech Biochem 77:235–242

    Article  CAS  Google Scholar 

  • Zhu Z, Zhang Q, Chen L, Ren S, Xu P, Tang Y, Luo D (2010) Higher specificity of the activity of low molecular weight fucoidan for thrombin-induced platelet aggregation. Thromb Res 125:419–426

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by Natural Science Foundation of China (No. 41376166), The Scientific and Technological Innovation Project Financially Supported by Qingdao National Laboratory for Marine Science and Technology (No. 2015ASKJ02), The Science and Technology Development Project of Shandong Province (No. 2014GHY115017), Special Fund for Marine Scientific Research in the Public Interest (201405040), and Special Found for Marine Scientific Research in Huangdao District (2014-04-11). And we thanked the anonymous reviewers.

Author contributions

Yingjie Xu designed the study, provided most of the data, and wrote the article; Quanbin Zhang co-authored the article and designed the study; Jing Wang co-did the experiments and provided some data; and Dali Luo and Delin Duan co-designed the study.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Quanbin Zhang or Delin Duan.

Ethics declarations

Experiments involving live animals were conducted in accordance with the “National Guide for the Care and Use of Laboratory Animals” and the “Regulations for the Administration of Affairs Concerning Experimental Animals” promulgated by the State Science and Technology Commission of Shandong Province. The study was approved by the ethics committee of Institute of Oceanology, Chinese Academy of Sciences.

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Xu, Y., Zhang, Q., Luo, D. et al. Low molecular weight fucoidan ameliorates the inflammation and glomerular filtration function of diabetic nephropathy. J Appl Phycol 29, 531–542 (2017). https://doi.org/10.1007/s10811-016-0942-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10811-016-0942-0

Keywords

Navigation