Skip to main content

Advertisement

Log in

Sulfated polysaccharide ascophyllan from Padina tetrastromatica enhances healing of burn wounds by ameliorating inflammatory responses and oxidative damage

  • Original Article
  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Sulfated polysaccharide ascophyllan from marine brown algae has been identified to have burn wound healing properties. Thus, we examined the effects of ascophyllan fraction (AF3) on the inflammatory response and oxidative damage in burn wounds. Full-thickness burn wounds in rats were then treated twice per day with topical AF3 ointment (5%), while control groups were treated with 10% povidone-iodine (positive control) and petroleum jelly-based ointment (negative control). The activity of cyclooxygenase-2 and myeloperoxidase and levels of C-reactive protein, nitric oxide, and proinflammatory cytokines (tumor necrosis factor-α, interleukin-6, and interleukin-1β) were observed to have significantly decreased in peripheral blood mononuclear cells, serum, and wound tissue of the group treated with AF3 ointment on day 8 after wounding. The expression of inducible nitric oxide synthase, endothelial nitric oxide synthase, and vascular endothelial growth factor at the mRNA level was determined to be upregulated in the wound tissue of the AF3 ointment-treated group. After treatment with AF3 ointment, the antioxidant enzyme activity and level of reduced glutathione were upregulated, whereas the content of thiobarbituric acid reactive substances decreased. Treatment of burn wounds using 5% AF3 ointment decreases oxidative damage associated with inflammation deceptively via inhibition of inflammatory enzymes, regulation of proinflammatory cytokines, upregulation of angiogenesis, and activity of antioxidant enzymes.

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

Similar content being viewed by others

References

  1. Baum CL, Arpey CJ (2005) Normal cutaneous wound healing: clinical correlation with cellular and molecular events. Dermatol Surg 31:674–686. https://doi.org/10.1111/j.1524-4725.2005.31612

    Article  CAS  PubMed  Google Scholar 

  2. Behm B, Babilas P, Landthaler M, Schreml S (2012) Cytokines, chemokines and growth factors in wound healing. J Euro Acad Dermatol Venereol 26:812–820. https://doi.org/10.1111/j.1468-3083.201

    Article  CAS  Google Scholar 

  3. Martin P, Leibovich SJ (2005) Inflammatory cells during wound repair: the good, the bad and the ugly. Trends Cell Biol 15:599–607. https://doi.org/10.1016/j.tcb.2005.09.002

    Article  CAS  PubMed  Google Scholar 

  4. Sandulache VC, Parekh A, Li-Korotky H, Dohar JE, Hebda PA (2007) Prostaglandin E2 inhibition of keloid fibroblast migration, contraction, and transforming growth factor (TGF)-β1–induced collagen synthesis. Wound Repair Regen 15:122–133. https://doi.org/10.1111/j.1524-475X.2006.00193.x

    Article  PubMed  Google Scholar 

  5. Futagami A, Ishizaki M, Fukuda Y, Kawana S, Yamanaka N (2002) Wound healing involves induction of cyclooxygenase-2 expression in rat skin. Lab Investig 82:1503–1513

    Article  CAS  PubMed  Google Scholar 

  6. Cals-Grierson MM, Ormerod D (2004) Nitric oxide function in the skin. Nitric Oxide 10:179–193. https://doi.org/10.1016/j.niox.2004.04.005

    Article  CAS  PubMed  Google Scholar 

  7. Parihar A, Parihar MS, Milner S, Bhat S (2008) Oxidative stress and anti-oxidative mobilization in burn injury. Burns 34:6–17. https://doi.org/10.1016/j.burns.2007.04.009

    Article  PubMed  Google Scholar 

  8. Wlaschek M, Singh K, Sindrilaru A, Crisan D, Scharffetter-Kochanek K (2019) Iron and iron-dependent reactive oxygen species in the regulation of macrophages and fibroblasts in non-healing chronic wounds. Free Radic Biol Med 133:262–275. https://doi.org/10.1016/j.freeradbiomed.2018.09.036

    Article  CAS  PubMed  Google Scholar 

  9. Liu DM, Sun BW, Sun ZW, Jin Q, Sun Y, Chen X (2008) Suppression of inflammatory cytokine production and oxidative stress by CO-releasing molecules—liberated CO in the small intestine of thermally-injured mice. Acta Pharmacol Sin 29:838–846. https://doi.org/10.1111/j.1745-7254.2008.00816.x

    Article  CAS  PubMed  Google Scholar 

  10. Agay D, Andriollo-Sanchez M, Claeyssen R, Touvard L, Denis J, Roussel AM, Chancerelle Y (2008) Interleukin-6, TNF-alpha and interleukin-1 beta levels in blood and tissue in severely burned rats. Eur Cytokine Netw 19:1–7

    CAS  PubMed  Google Scholar 

  11. Ferraro V, Cruz IB, Jorge RF, Malcata FX, Pintado ME, Castro PM (2010) Valorisation of natural extracts from marine source focused on marine by-products: a review. Food Res Int 43:2221–2233. https://doi.org/10.1016/j.foodres.2010.07.034

    Article  Google Scholar 

  12. Yeo M, Jung WK, Kim GH (2012) Fabrication, characterisation and biological activity of phlorotannin-conjugated PCL/b-TCP composite scaffolds for bone tissue regeneration. J Mater Chem 22:3568–3577

    Article  CAS  Google Scholar 

  13. Pomi VH, Mourao PAS (2008) Structure, biology, evolution and medical importance of sulphated fucans and galactans. Glycobiol 18:1016–1027. https://doi.org/10.1093/glycob/cwn085

    Article  CAS  Google Scholar 

  14. Nakayasu S, Soegima R, Yamaguchi K, Oda T (2009) Biological activities of fucose-containing polysaccharide ascophyllan isolated from the brown alga Ascophyllum nodosum. Biosci Biotechnol Biochem 73:961–964. https://doi.org/10.1271/bbb.80845

    Article  CAS  PubMed  Google Scholar 

  15. Jiang Z, Abu R, Isaka S, Nakazono S, Ueno M, Okimura T, Oda T (2014) Inhibitory effect of orally-administered sulfated polysaccharide ascophyllan isolated from Ascophyllum nodosum on the growth of sarcoma-180 solid tumor in mice. Anticancer Res 34:1663–1671

    CAS  PubMed  Google Scholar 

  16. Abu R, Jiang Z, Ueno M, Okimura T, Yamaguchi K, Oda T (2013) In vitro antioxidant activities of sulfated polysaccharide ascophyllan isolated from Ascophyllum nodosum. Int J Biol Macromol 59:305–312. https://doi.org/10.1016/j.ijbiomac.2013.04.035

    Article  CAS  PubMed  Google Scholar 

  17. Mohsin S, Kurup GM, Mahadevan R (2013) Effect of ascophyllan from brown algae Padina tetrastromatica on inflammation and oxidative stress in carrageenan-induced rats. Inflammation 36:1268–1278

    Article  CAS  PubMed  Google Scholar 

  18. Sulaiman M, Mahadevan RK, Kurup GM (2019) Effect of ascophyllan from brown algae Padina tetrastromatica on cell migration and extracellular matrix stabilisation in burn wounds. Curr Bioact Compd 15:562–572. https://doi.org/10.2174/1573407214666180327123118

    Article  CAS  Google Scholar 

  19. Radhika A, Jacob SS, Sudhakaran PR (2007) Influence of oxidatively modified LDL on monocyte-macrophage differentiation. Mol Cell Biochem 305:133–143. https://doi.org/10.1007/s11010-007-9536-0

    Article  CAS  PubMed  Google Scholar 

  20. Ben Assayag E, Shenhar-Tsarfaty S, Bova I, Berliner S, Usher S, Peretz H, Shapira I, Bornstein NM (2009) Association of the -757TNC polymorphism in the CRP gene with circulating C-reactive protein levels and carotid atherosclerosis. Thromb Res 124:458–462. https://doi.org/10.1016/j.thromres.2009.04.008

    Article  CAS  PubMed  Google Scholar 

  21. Bories PN, Bories C (1995) Nitrate determination in biological fluids by an enzymatic one step assay with nitrate reductase. Clin Chem 41:904–907. https://doi.org/10.1093/clinchem/41.6.904

    Article  CAS  PubMed  Google Scholar 

  22. Stark JM, Van Egmond AW, Zimmerman JJ, Carabell SK, Tosi MF (1992) Detection of enhanced neutrophil adhesion to parainfluenza-infected airway epithelial cells using a modified myeloperoxidase assay in a microtiter format. J Virol Methods 40:225–242. https://doi.org/10.1016/0166-0934(92)90071-K

    Article  CAS  PubMed  Google Scholar 

  23. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2 − ΔΔCT method. Methods 25:402–408. https://doi.org/10.1006/meth.2001.1262

    Article  CAS  PubMed  Google Scholar 

  24. Beyer WF Jr, Fridovich I (1987) Assaying for superoxide dismutase activity: some large consequences of minor changes in conditions. Anal Biochem 161:559–566. https://doi.org/10.1016/0003-2697(87)90489-1

    Article  CAS  PubMed  Google Scholar 

  25. Aebi H (1984) [13] Catalase in vitro. In: Packer L (ed) Methods in enzymology, vol 105. Academic Press, Orlando, pp 121–126. https://doi.org/10.1016/S0076-6879(84)05016-3

    Chapter  Google Scholar 

  26. Flohe L, Gunzler WA (1984) [12] Assays of glutathione peroxidase. In: Packer L (ed) Methods in enzymology, vol 105. Academic Press, Berlin, pp 114–120. https://doi.org/10.1016/S0076-6879(84)05015-1

    Chapter  Google Scholar 

  27. Sedlak J, Lindsay RH (1968) Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman’s reagent. Anal Biochem 25:192–205

    Article  CAS  PubMed  Google Scholar 

  28. Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358

    Article  CAS  PubMed  Google Scholar 

  29. Shi L (2016) Bioactivities, isolation and purification methods of polysaccharides from natural products: a review. Int J Biol Macromol 92:37–48. https://doi.org/10.1016/j.ijbiomac.2016.06.100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Berry E, Liu Y, Chen L, Guo AM (2017) Eicosanoids: emerging contributors in stem cell-mediated wound healing. Prostaglandins Other Lipid Med 132:17–24. https://doi.org/10.1016/j.prostaglandins.2016.11.001

    Article  CAS  Google Scholar 

  31. Nafiu AB, Rahman MT (2015) Anti-inflammatory and antioxidant properties of unripe papaya extract in an excision wound model. Pharm Biol 53:662–671. https://doi.org/10.3109/13880209.2014.936470

    Article  PubMed  Google Scholar 

  32. Bertsch T, Triebel J, Bollheimer C, Christ M, Sieber C, Fassbender K, Heppner HJ (2015) C-reactive protein and the acute phase reaction in geriatric patients. Z Gerontol Geriatr 48:595–600. https://doi.org/10.1007/s00391-015-0938-4

    Article  PubMed  Google Scholar 

  33. Ridker PM (2016) From C-reactive protein to interleukin-6 to interleukin-1: moving upstream to identify novel targets for atheroprotection. Circ Res 118:145–156. https://doi.org/10.1161/CIRCRESAHA.115.306656

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Del Giudice M, Gangestad SW (2018) Rethinking IL-6 and CRP: why they are more than inflammatory biomarkers, and why it matters. Brain Behav Immun 70:61–75. https://doi.org/10.1016/j.bbi.2018.02.013

    Article  CAS  PubMed  Google Scholar 

  35. Wang J (2018) Neutrophils in tissue injury and repair. Cell Tissue Res 371:531–539. https://doi.org/10.1007/s00441-017-2785-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Kandhare AD, Alam J, Patil MV, Sinha A, Bodhankar SL (2016) Wound healing potential of naringin ointment formulation via regulating the expression of inflammatory, apoptotic and growth mediators in experimental rats. Pharma Biol 54:419–432. https://doi.org/10.3109/13880209.2015.1038755

    Article  CAS  Google Scholar 

  37. Dwivedi D, Dwivedi M, Malviya S, Singh V (2017) Evaluation of wound healing, anti-microbial and antioxidant potential of Pongamia pinnata in wistar rats. J Tradit Complement Med 7:79–85. https://doi.org/10.1016/j.jtcme.2015.12.002

    Article  PubMed  Google Scholar 

  38. Zhou X, Wang H, Zhang J, Li X, Wu Y, Wei Y, Zhao Q (2017) Functional poly (ε caprolactone)/chitosan dressings with nitric oxide-releasing property improve wound healing. Acta Biomater 54:128–137. https://doi.org/10.1016/j.actbio.2017.03.011

    Article  CAS  PubMed  Google Scholar 

  39. Kapoor M, Howard R, Hall I, Appleton I (2004) Effects of epicatechin gallate on wound healing and scar formation in a full thickness incisional wound healing model in rats. Am J Pathol 165:299–307. https://doi.org/10.1016/S0002-9440(10)63297-X

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Nie X, Zhang H, Shi X, Zhao J, Chen Y, Wu F, Yang J, Li X (2020) Asiaticoside nitric oxide gel accelerates diabetic cutaneous ulcers healing by activating Wnt/β-catenin signaling pathway. Int Immunopharmacol 79:106109. https://doi.org/10.1016/j.intimp.2019.106109

    Article  CAS  PubMed  Google Scholar 

  41. Kumar V, Sharma A (2010) Neutrophils: Cinderella of innate immune system. Int Immunopharmacol 10:1325–1334. https://doi.org/10.1016/j.intimp.2010.08.012

    Article  CAS  PubMed  Google Scholar 

  42. Okado-Matsumoto A, Fridovich I (2001) Subcellular distribution of superoxide dismutases (SOD) in rat liver Cu, Zn-SOD in mitochondria. J Biol Chem 276:38388–38393. https://doi.org/10.1074/jbc.M105395200

    Article  CAS  PubMed  Google Scholar 

  43. Grzelak A, Rychlik B, Bartosz G (2000) Reactive oxygen species are formed in cell culture media. Acta Biochim Pol 47:1197–1198

    CAS  PubMed  Google Scholar 

  44. Sellimi S, Maalej H, Rekik DM, Benslima A, Ksouda G, Hamdi M, Sahnoun Z, Nasri M, Hajji M (2018) Antioxidant, antibacterial and in vivo wound healing properties of laminaran purified from Cystoseira barbata seaweed. Int J Biol Macromol 119:633–644. https://doi.org/10.1016/j.ijbiomac.2018.07.171

    Article  CAS  PubMed  Google Scholar 

  45. Fan J, Wu Z, Zhao T, Sun Y, Ye H, Xu R, Zeng X (2014) Characterization, antioxidant and hepatoprotective activities of polysaccharides from Ilex latifolia Thunb. Carbohydr Polym 101:990–997. https://doi.org/10.1016/j.carbpol.2013.10.037

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thankfully acknowledge a research grant from the University Grant Commission as Fellowship for Research to Meritorious Students.

Funding

The research is financially supported by the University Grant Commission.

Author information

Authors and Affiliations

Authors

Contributions

The experiments were designed by MS and GMK; performed by MS and MR; and analyzed by MS, SRA, and GMK. The manuscript was written by MS and SRA and reviewed and edited by GMK and MR. The final manuscript was read and approved by all authors.

Corresponding author

Correspondence to Mohsin Sulaiman.

Ethics declarations

Conflicts of interest

The authors declare no conflict of interest.

Ethics approval

This study has been approved by the Ethical Committee of the University of Kerala in accordance with the established ethics for lab animal usage and maintenance by the Government of India (Sanctioned Number IAEC-KU 09-10/3(1)-BC-GMK).The experiments were conducted according to guidelines of the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA), Government of India for lab animals use and care.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 299 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sulaiman, M., Alyileili, S.R., Raghavankutty, M. et al. Sulfated polysaccharide ascophyllan from Padina tetrastromatica enhances healing of burn wounds by ameliorating inflammatory responses and oxidative damage. Mol Biol Rep 47, 8701–8710 (2020). https://doi.org/10.1007/s11033-020-05914-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-020-05914-5

Keywords

Navigation