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Antinociceptive and anti-inflammatory effects of a mucin-binding agglutinin isolated from the red marine alga Hypnea cervicornis

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Abstract

The agglutinin from the red marine alga Hypnea cervicornis (HCA) was tested in models of nociception and inflammation. The role of carbohydrate-binding sites and the systemic toxicity were assessed. HCA (10−1, 1, and 10 mg/kg) administered i.v. to mice inhibited writhes induced by acetic acid and, at 10 mg/kg, inhibited the second phase of the formalin test, but did not alter the response latency in the hot-plate test. HCA (1 mg/kg) administered i.v. to rats reduced carrageenan-induced paw edema at 1, 2, and 3 h after challenge, but not edema induced by dextran. The neutrophil migration induced by both N-formyl-methionyl-leucyl-phenylalanine (fMLP) and carrageenan was inhibited by HCA at 10−1, 1, and 10 mg/kg. The combination of HCA (1 mg/kg) and its ligand mucin reversed the lectin inhibitory effect on carrageenan-induced neutrophil migration and acetic acid-induced writhes. The i.v. treatment of rats with HCA (1 mg/kg) for 7 days did not affect body mass; liver, kidney or heart wet weight; blood leukocyte counts; urea, creatinine or serum transaminase activity; or macroscopy of the organs examined. In short, H. cervicornis agglutinin showed important antinociceptive and anti-inflamatory activity via interaction with the lectin carbohydrate-binding site.

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Fig. 1a, b
Fig. 2

Abbreviations

HCA:

Hypnea cervicornis agglutinin

ALT:

Alanine amine transferase

AST:

Aspartate amine transferase

Cg:

Carrageenan

fMLP:

N-formyl-methionyl-leucyl-phenyl alanine

Dexa:

Dexamethasone

References

  • Ainouz IL, Sampaio AH (1991) Screening of Brazilian marine algae for hemagglutinins. Botanica Marina 34:211–214

    Article  CAS  Google Scholar 

  • Ainouz IL, Sampaio AH, Freitas ALP, Benevides NMB, Mapurunga S (1995) Comparative study on hemagglutinins from the red algae Bryothamnion seaforthii and B. triquetrum. Rev Bras Fisiol Vegetal 7:15–19

    CAS  Google Scholar 

  • Alencar NMN, Teixeira EH, Assreuy MAS, Cavada BS, Flores CA, Ribeiro RA (1999) Leguminous lectins as tools for studying the role of sugar residues in leukocyte recruitment. Mediators Inflamm 8:107–113

    Article  PubMed  CAS  Google Scholar 

  • Alencar NMN, Assreuy AMS, Alencar VB, Melo SC, Ramos MV, Cavada BS, Cunha FQ, Ribeiro RA (2003) The galactose-binding lectin from Vatairea macrocarpa seeds induces in vivo neutrophil migration by indirect mechanism. Int J Biochem Cell Biol 35:1674–1681

    Article  PubMed  CAS  Google Scholar 

  • Alencar NMN, Assreuy AMS, Cavada BS, Ribeiro RA (2004) Vaitarea macrocarpa lectin induces paw edema with leukocyte infiltration. Protein Pept Lett 11:195–200

    Article  PubMed  CAS  Google Scholar 

  • Alencar NMN, Cavalcante CF, Vasconcelos MP, Leite KB, Aragão KS, Assreuy AMS, Nogueira NAP, Cavada BS, Vale MR (2005) Anti-inflammatory and anti-microbial effect of lectin from Lonchocarpus sericeus seeds in an experimental model of infectious peritonitis. J Pharm Pharmacol 57:919–922

    Article  PubMed  CAS  Google Scholar 

  • Alencar VBM, Alencar NMN, Assreuy AMS, Mota ML, Brito GAC, Aragão KS, Bittencourt FS, Pinto VPT, Debray H, Ribeiro RA, Cavada BS (2005a) Pro-inflammatory effect of Arum maculatum lectin and role of resident cells. Int J Biochem Cell Biol 37:1805–1814

    Article  PubMed  CAS  Google Scholar 

  • Alencar VBM, Brito GAC, Alencar NMN, Assreuy AMS, Pinto VPT, Teixeira EH, Souza EP, Debray H, Ribeiro RA, Cavada BS (2005b) Helianthus tuberosus agglutinin directly induces neutrophil migration, which can be modulated/inhibited by resident mast cells. Biochem Cell Biol 83:659–666

    Article  PubMed  CAS  Google Scholar 

  • Alencar VBM, Assreuy AMS, Alencar NMN, Meireles AVP, Mota MRL, Aragão KS, Cajazeiras JB, Nagano CS, Brito GAC, Silva LIMM, Pinto VPT, Sampaio AH, Debray H, Cavada BS, Ribeiro RA (2005c) Lectin of Pisum arvense seeds induces in vivo and in vitro neutrophil migration. J Pharm Pharmacol 57:375–381

    Article  PubMed  CAS  Google Scholar 

  • Alencar NMN, Assreuy AMS, Havt A, Benevides RG, Moura TR, Sousa RB, Ribeiro RA, Cunha FQ, Cavada BS (2007) Vatairea macrocarpa (Leguminosae) lectin activates cultured macrophages to release chemotactic mediators. Naunyn-Schmiedebergs Arch Pharmacol 374:275–282

    Article  PubMed  CAS  Google Scholar 

  • Assreuy MAS, Shibuya MD, Martins GJ, Sousa MLP, Cavada BS, Moreira RA, Oliveira JTA, Ribeiro RA, Flores CA (1997) Anti-inflammatory effect of glucose-mannose binding lectins isolated from Brazilian beans. Mediators Inflamm 6:201–210

    Article  CAS  PubMed  Google Scholar 

  • Assreuy AMS, Martins GJ, Moreira ME, Brito GAC, Cavada BS, Ribeiro RA, Flores CA (1999) Prevention of cyclophosphamide-induced hemorrhagic cystitis by glucose-mannose binding plant lectins. J Urol 161:1988–1993

    Article  PubMed  CAS  Google Scholar 

  • Bento CA, Cavada BS, Oliveira JT, Moreira RA, Barja-Fidalgo C (1993) Rat paw edema and leukocyte immigration induced by plant lectins. Agents Actions 38:48–54

    Article  PubMed  CAS  Google Scholar 

  • Beuth J, Ko HL, Pulverer G, Uhlenbruck G, Pichlmaier H (1995) Importance of lectins for the prevention of bacterial infection and cancer metastases. Glycoconj J 12:1–6

    Article  PubMed  CAS  Google Scholar 

  • Carvalho JTC, Teixeira JRM, Souza PJC, Bastos JK, Filho DS, Sarti SJ (1996) Preliminary studies of analgesic and anti-inflammatory properties of Caesalpinea ferrea crude extract. J Ethnopharm 53:175–178

    Article  CAS  Google Scholar 

  • Correa CR, Kyke DJ, Chakraverty S, Calixto JB (1996) Antinociceptive profile of the pseudopepitide B2 bradykinin and receptor antagonist NPC 18688 in mice. Br J Pharmacol 117:552–558

    PubMed  CAS  Google Scholar 

  • Cunha TM, Verri Jr WA, Silva JS, Poole S, Cunha FQ, Ferreira SH (2005) A cascade of cytokines mediates mechanical inflammatory hypernociception in mice. Proc Natl Acad Sci USA 102:1755–1760

    Article  PubMed  CAS  Google Scholar 

  • Eddy NB, Leinback D (1953) Synthetic analgesics. II. Dithienylbutenyl- and dithienylbutylamines. J Pharmacol Exp Ther 107:385–393

    PubMed  CAS  Google Scholar 

  • Fasmer OB, Berge OG, Hole K (1985) Changes in nociception after lesions of descending serotonergic pathways induced with 5,6-dihydroxytryptamine. Different effects in the formalin and tail-flick tests. Neuropharmacology 24:729–734

    Article  PubMed  CAS  Google Scholar 

  • Ferreira SH (1979) A new method for measuring variations of rats paw volumes. J Pharm Pharmacol 31:648

    PubMed  CAS  Google Scholar 

  • Guzman S, Gato A, Calleja JM (2001) Antiinflammatory, analgesic and free radical scavenging activities of the marine microalgae Chlorella stigmatophora and Phaeodactylum tricornutum. Phytother Res 15:224–230

    Article  PubMed  CAS  Google Scholar 

  • Hajare SW, Chandra S, Charma J, Tandan SK, Lal J, Telang AG (2001) Anti-inflammatory activity of Dalbergia sissoo leaves. Fitoterapia 72:131–139

    Article  PubMed  CAS  Google Scholar 

  • Ikeda Y, Ueno A, Naraba H, Oh-ishi S (2001) Involvement of vanilloid receptor VR1 and prostanoids in the acid-induced writhing responses of mice. Life Sci 69:2911–2919

    Article  PubMed  CAS  Google Scholar 

  • Joly AB (1965) Flora marinha do litoral norte do estado de São Paulo e regiões circunvizinhas. Bol Fac Filosof Ciências Letr Univ São Paulo 21:1–393

    Google Scholar 

  • Koster R, Anderson M, De Beer EJ (1959) Acetic acid for analgesic screening. Fed Proc 18:412–414

    Google Scholar 

  • Landucci ECT, Antunes E, Donato JL, Faro R, Hyslop S, Marangoni S, Oliveira B, Cirino G, De Nucci G (1995) Inhibition of carrageenan-induced rat paw edema by crotapotin, a polypeptide complexed with phospholipase A2. Brit J Pharmacol 114:578–583

    CAS  Google Scholar 

  • Levine JD, Lau W, Kwiat G, Goetzl EJ (1984) Leukotriene B4 produces hyperalgesia that is dependent on polymorphonuclear leukocytes. Science 225:743–745

    Article  PubMed  CAS  Google Scholar 

  • Ley K (2002) Integration of inflammatory signals by rolling neutrophils. Immunol Rev 186:8–18

    Article  PubMed  CAS  Google Scholar 

  • Lim SN, Cheung PC, Ooi VE, Ang PO (2002) Evaluation of antioxidative activity of extracts from a brown seaweed Sargassum siliquastrum. J Agric Food Chem 50:3862–3866

    Article  PubMed  CAS  Google Scholar 

  • Lo TN, Almeida AP, Beaven MA (1982) Dextran and carrageenin evoke different inflammatory response in rat with respect to composition of infiltrates and effect of indomethacin. J Pharmacol Exp Ther 221:261–267

    PubMed  CAS  Google Scholar 

  • Malmberg AB, Yaksh TL (1995) The effect of morphine on formalin-evoked behaviour and spinal release of excitatory amino acids and prostaglandin E2 using microdialysis in conscious rats. Br J Pharmacol 114:1069–1075

    PubMed  CAS  Google Scholar 

  • Mota MR, Criddle DN, Alencar NM, Gomes RC, Meireles AV, Santi-Gadelha T, Gadelha CA, Oliveira CC, Benevides RG, Cavada BS, Assreuy AMS (2006) Modulation of acute inflammation by a chitin-binding lectin from Araucaria angustifolia seeds via mast cells. Naunyn-Schmiedebergs Arch Pharmacol 374:1–10

    Article  PubMed  CAS  Google Scholar 

  • Nagano CS, Debray H, Nascimento KS, Pinto VPT, Cavada BS, Sampaio SS, Farias WRL, Sampaio AH, Calvete JJ (2005) HCA and HML isolated from the red marine algae Hypnea cervicornis and Hypnea musciformis define a novel lectin family. Protein Sci 14:2167–2176

    Article  PubMed  CAS  Google Scholar 

  • Napimoga MH, Cavada BS, Alencar NMN, Mota ML, Bitencourt FS, Alves-Filho JC, Grespan R, Gonçalves RB, Clemente-Napimoga JT, Freitas A, Parada CA, Ferreira SH, Cunha FQ (2007) Lonchocarpus sericeus lectin decreases leukocyte migration and mechanical hypernociception by inhibiting cytokine and chemokines production. Int Immunopharmacol 7:824–835

    Article  PubMed  CAS  Google Scholar 

  • Nascimento KS, Nagano CS, Nunes EV, Rodrigues RF, Goersch GV, Cavada BS, Calvete JJ, Saker-Sampaio S, Farias WR, Sampaio AH (2006) Isolation and characterization of a new agglutinin from the red marine algae Hypnea cervicornis J. Agardh. Biochem Cell Biol 84:49–54

    Article  CAS  Google Scholar 

  • Nemirovsky A, Chen L, Zelma V, Jurna I (2001) The antinociceptive effect of the combination of spinal morphine with systemic morphine or buprenorphine. Anesthesiol Analgesic 93:197–203

    Article  CAS  Google Scholar 

  • Neves SA, Dias-Baruffi M, Freitas ALP, Roque-Barreira MC (2001) Neutrophil migration induced in vivo and in vitro by marine algal lectins. Inflamm Res 50:486–490

    Article  PubMed  CAS  Google Scholar 

  • Neves SA, Freitas ALP, Souza BWS, Rocha MLA, Correia MVO, Sampaio DA, Viana GSB (2007) Antinociceptive properties in mice of a lectin isolated from the marine alga Amansia multifida Lamouroux. Braz J Med Biol Res 40:127–134

    PubMed  CAS  Google Scholar 

  • Omote K, Kawamata T, Kawamata M, Namiki A (1998) Formalin-induced release of excitatory amino acids in the skin of the rat hindpaw. Brain Res 787:161–164

    Article  PubMed  CAS  Google Scholar 

  • Ozaki Y (1990) Anti-inflammatory effects of Curcuma xanthorrhiza Roxb, and its active principle. Chem Pharm Bull 38:1045–1048

    PubMed  CAS  Google Scholar 

  • Panés J, Perry M, Granger DN (1999) Leukocyte-endothelial cell adhesion: avenues for therapeutic intervention. Br J Pharmacol 126:537–550

    Article  PubMed  Google Scholar 

  • Peumans WJ, Van Damme EJL (1995) Lectins as plant defense proteins. Plant Physiol 109:347–352

    Article  PubMed  CAS  Google Scholar 

  • Ribeiro RA, Souza-Filho MVP, Souza MHLP, Oliveira SHP, Costa CHS, Cunha FQ, Ferreira SH (1996) Role of resident mast cells and macrophages in the neutrophil migration induced by LTB4, fMLP and C5a des arg. Int Arch Allergy Immunol 112:27–35

    Article  Google Scholar 

  • Ribeiro RA, Vale ML, Thomazzi SM, Paschoalato AB, Poole S, Ferreira SH, Cunha FQ (2000) Involvement of resident macrophages and mast cells in the writhing nociceptive response induced by zymosan and acetic acid in mice. Eur J Pharmacol 387:111–118

    Article  PubMed  CAS  Google Scholar 

  • Santi-Gadelha T, de Almeida Gadelha CA, Aragão KS, Oliveira CC, Mota MRL, Gomes RC, Freitas AP, Toyama MH, Oliveira TD, Alencar NMN, Criddle DN, Assreuy AM, Cavada BS (2006) Purification and biological effects of Araucaria angustifolia (Araucariaceae) seed lectin. Biochem Biophys Res Commun 50:1050–1055

    Article  CAS  Google Scholar 

  • Santodomingo-Garzon T, Cunha TM, Verri Jr WA, Valério DA, Parada CA, Poole S, Ferreira SH, Cunha FQ (2006) Atorvastatin inhibits inflammatory hypernociception. Br J Pharmacol 149:14–22

    Article  PubMed  CAS  Google Scholar 

  • Santos ARS, Calixto JB (1997) Further evidence for the involvement of tachycinin receptor subtypes in formalin and capsaicin models of pain in mice. Neuropeptides 31:381–389

    Article  PubMed  CAS  Google Scholar 

  • Santucci L, Fiorucci S, Giansanti M, Brunori PM, Di Matteo FM, Morelli A (1994) Pentoxifylline prevents indomethacin induced acute gastric mucosal damage in rats: role of tumour necrosis factor alpha. Gut 35:909–915

    Article  PubMed  CAS  Google Scholar 

  • Shibata M, Ohkubo T, Takahasi H, Inoki R (1989) Modified formalin test: characteristic biphasic pain response. Pain 38:347–352

    Article  PubMed  CAS  Google Scholar 

  • Siddqiui S, Shyum SBN, Usmanghani K, Shameel M (1993) Antibacterial activity and fatty acid composition of the extract from Hypnea musciformis (Gigartinales, Rhodophyta). Pak J Pharm Sci 6:45–51

    PubMed  Google Scholar 

  • Souza GE, Ferreira SH (1985) Blockade by antimacrophage serum of the migration of PMN neutrophils into the inflamed peritoneal cavity. Agents Actions 17:97–103

    Article  PubMed  Google Scholar 

  • Souza GE, Cunha FQ, Mello R, Ferreira SH (1988) Neutrophil migration induced by inflammatory stimuli is reduced by macrophage depletion. Agents Actions 24:377–380

    Article  PubMed  CAS  Google Scholar 

  • Srinivasan K, Muruganandan S, Lal J, Chandra S, Tandan SK, Prakash VR (2001) Evaluation of anti-inflammatory activity of Pongamia pinnata leaves in rats. J Ethnopharmacol 78:151–157

    Article  PubMed  CAS  Google Scholar 

  • Taylor WR (1960) Marine algae of the eastern tropical and sub-tropical coast of Americas. University of Michigan Press, Ann Arbor

    Google Scholar 

  • Tedder TF, Steeber DA, Chen A, Enegel P (1995) The selectins: vascular adhesion molecules. Faseb J 9:866–873

    PubMed  CAS  Google Scholar 

  • Tjølsen A, Hole K (1997) Animal models of analgesia. In: Dickenson A, Besson J (eds) The pharmacology of pain, vol. 130. Springer Verlag, Berlin, pp 1–20

    Google Scholar 

  • Tjølsen A, Berge DG, Hunskaar S, Rosland JH, Hole K (1992) The formalin test: an evaluation of the method. Pain 51:5–17

    Article  PubMed  Google Scholar 

  • Vanegas H, Schaible HG (2001) Prostaglandins and ciclooxygenases in spinal cord. Prog Neurobiol 64:327–363

    Article  PubMed  CAS  Google Scholar 

  • Verri WA Jr, Schivo IR, Cunha TM, Liew FY, Ferreira SH, Cunha FQ (2004) Interleukin-18 induces mechanical hypernociception in rats via endothelin acting on ETB receptors in a morphine sensitive manner. J Pharmacol Exp Ther 310:710–717

    Article  PubMed  CAS  Google Scholar 

  • Viana GSB, Freitas ALP, Lima MML, Vieira LAP, Andrade MCH, Benevides NMB (2002) Antinociceptive activity of sulfated carbohydrates from the red algae Bryothamnion seaforthii (Turner) Kütz. and B. triquetrum (S.G. Gmel.) M. Howe. Braz J Med Biol Res 35:713–722

    Article  PubMed  CAS  Google Scholar 

  • Vieira LAP, Freitas ALP, Feitosa JPA, Silva DC, Viana GSB (2004) The alga Bryothamnion seaforthii contains carbohydrates with antinociceptive activity. Braz J Med Biol Res 37:1071–1079

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

This work was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Fundação Cearense de Amparo à Pesquisa (FUNCAP). Drs. Alexandre H. Sampaio, Ana M. S. Assreuy, Benildo S. Cavada and Nylane M.N. de Alencar are senior investigators of CNPq (Brazil). Dr. A. Leyva provided English editing of the manuscript.

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Bitencourt, F.d.S., Figueiredo, J.G., Mota, M.R.L. et al. Antinociceptive and anti-inflammatory effects of a mucin-binding agglutinin isolated from the red marine alga Hypnea cervicornis . Naunyn-Schmied Arch Pharmacol 377, 139–148 (2008). https://doi.org/10.1007/s00210-008-0262-2

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