The marine environment is an extraordinary reservoir of bioactive natural products, many of which exhibit chemical and structural features not found in terrestrial natural products. In this regard, the aim of this study was to investigate the possible antinociceptive and anti-inflammatory activities of a crude methanolic extract of the red alga Bryothamnion triquetrum (BT-MeOH) in murine models. Groups of Swiss mice of both sexes (25–30 g) were used throughout the experiments. The potential antinociceptive of BT-MeOH was evaluated by means of the following tests: acetic acid-induced writhing, hot-plate test and glutamate- and formalin-induced nociception. The anti-inflammatory activity of BT-MeOH was investigated using the zymosan A-induced peritonitis test. The tests were conducted using 100 mg/kg (p.o.) BT-MeOH, 33.3 mg/kg (p.o.) dipyrone, 35.7？mg/kg (p.o.) indomethacin and 5.7 mg/kg (s.c.) morphine. The extract and all standard drugs were administered 40 min before the nociceptive/inflammatory stimulus. In the acetic acid-induced writhing test, BT-MeOH and dipyrone inhibited the nociceptive response by 55.9% (22.2 ± 2.0 writhings; p < 0.01) and 80.9% (9.6 ± 2.1 writhings; p < 0.01). In the hot-plate test, BT-MeOH did not increase the latency time of the animals in the time evaluated. In addition, BT-MeOH inhibited glutamate-induced nociception by 50.1%. While BT-MeOH did not inhibit the neurogenic phase in formalin-induced nociception, the inflammatory phase was inhibited by 53.1% (66.8 ± 14.2 s; p < 0.01). Indomethacin inhibited the inflammatory phase by 60.2% (56.8 ± 8.7 s; p < 0.01). In the zymosan-induced peritonitis test, BT-MeOH inhibited 55.6% (6.6 ± 0.2 × 10 6 leukocytes/mL; p < 0.01) of leukocyte migration, while indomethacin inhibited 78.1% (3.2 ± 0.1 × 10 6 leukocytes/mL; p < 0.01). Based on the results obtained in this study, we conclude that BT-MeOH has peripheral antinociceptive and anti-inflammatory activities. However, more studies need to be conducted to confirm these properties.
References
[1]
Kim, S.; Wijesekara, I. Development and biological activities of marine-derived bioactive peptides: A review. J. Funct. Foods 2010, 2, 1–9, doi:10.1016/j.jff.2010.01.003.
[2]
Almeida, C.L.F.; Falc？o, H.S.; Lima, G.R.M.; Montenegro, C.A.; Lira, N.S.; Athayde-Filho, P.F.; Rodrigues, L.C.; Souza, M.F.V.; Barbosa-Filho, J.M.; Batista, L.M. Bioactivities from marine algae of the genus Gracilaria. Int. J. Mol. Sci. 2011, 12, 4550–4573, doi:10.3390/ijms12074550.
[3]
Queiroz, T.M.; Machado, N.T.; Furtado, F.F.; Oliveira-Filho, A.A.; Alustau, M.C.; Figueiredo, C.S.; Miranda, G.E.C.; Barbosa-Filho, J.M.; Braga, V.A.; Medeiros, I.A. Vasorelaxation, induced by Dictyota pulchella (Dictyotaceae), a brown alga, is mediated via inhibition of calcium influx in rats. Mar. Drugs 2011, 9, 2075–2088.
[4]
Souza, E.T.; Lira, D.P.; Queiroz, A.C.; Silva, D.J.C.; Aquino, A.B.; Mella, E.A.C.; Lorenzo, V.L.; Miranda, G.E.C.; Araújo-Júnior, J.X.; Chaves, M.C.O.; et al. The antinociceptive and anti-inflammatory activities of caulerpin, a bisindole alkaloid isolated from seaweeds of the genus Caulerpa. Mar. Drugs 2009, 7, 689–704, doi:10.3390/md7040689.
[5]
Kijjoa, A.; Sawangwong, P. Drugs and cosmetics from the sea. Mar. Drugs 2004, 2, 73–82, doi:10.3390/md202073.
[6]
La Barre, S.; Potin, P.; Leblanc, C.; Delage, L. The halogenated metabolism of brown algae (Phaeophyta), its biological importance and its environmental significance. Mar. Drugs 2010, 8, 988–1010.
[7]
Lira, N.S.; Montes, R.C.; Tavares, J.F.; Silva, M.S.; Cunha, E.V.L.; Athayde-Filho, P.F.; Rodrigues, L.C.; Dias, C.S.; Barbosa-Filho, J.M. Brominated compounds from marine sponges of the genus Aplysina and a compilation of their 13C NMR spectral data. Mar. Drugs 2011, 9, 2316–2368, doi:10.3390/md9112316.
[8]
Bergmann, W.; Feeney, R. Contribution to the study of marine sponges. 32. The nucleosides of sponges. J. Org. Chem. 1951, 16, 981–987, doi:10.1021/jo01146a023.
Jha, R.K.; Zi-rong, X. Biomedical compounds from marine organisms. Mar. Drugs 2004, 2, 123–146, doi:10.3390/md203123.
[11]
Koopmans, M.; Martens, D.; Wijffels, R. Towards commercial production of sponge medicines. Mar. Drugs 2009, 7, 787–802, doi:10.3390/md7040787.
[12]
Balan, V.; Nangia-Makker, P.; Raz, A. Galectins as cancer biomarkers. Cancers 2010, 2, 592–610, doi:10.3390/cancers2020592.
[13]
Proksch, P.; Edrada, R.A.; Ebel, R. Drugs from the seas—Current status and microbiological implications. Appl.Microbiol. Biotechnol. 2002, 59, 125–134, doi:10.1007/s00253-002-1006-8.
[14]
Mayer, A.M.S.; Glaser, K.B.; Cuevas, C.; Jacobs, R.S.; Kem, W.; Little, R.D.; Mcintosh, J.M.; Newman, D.J.; Potts, B.C.; Shuster, D.E. The odyssey of marine pharmaceuticals: A current pipeline perspective. Trends Pharmacol.Sci. 2010, 31, 255–265, doi:10.1016/j.tips.2010.02.005.
[15]
Zhang, J.L.; Xia, W.S.; Liu, P.; Cheng, Q.Y.; Tahirou, T.; Gu, W.X.; Li, B. Chitosan modification and pharmaceutical/biomedical applications. Mar. Drugs 2010, 8, 1962–1987, doi:10.3390/md8071962.
[16]
O’Sullivan, L.; Murphy, B.; McLoughlin, P.; Duggan, P.; Lawlor, P.G.; Hughes, H.; Gardiner, G.E. Prebiotics from marine macroalgae for human and animal health applications. Mar. Drugs 2010, 8, 2038–2064, doi:10.3390/md8072038.
[17]
Matta, C.B.B.; Souza, E.T.; Queiroz, A.C.; Lira, D.P.; Araújo, M.V.; Cavalcante-Silva, L.H.A.; Miranda, G.E.C.; Araújo-Júnior, J.X.; Barbosa-Filho, J.M.; Santos, B.V.O.; et al. Antinociceptive and anti-inflammatory activity from algae of the genus Caulerpa. Mar. Drugs 2011, 9, 307–318, doi:10.3390/md9030307.
[18]
Paula, J.C.; Vallim, M.A.; Teixeira, V.L. What are and where are the bioactive terpenoids metabolites from Dictyotaceae (Phaeophyceae). Rev. Bras. Farmacogn. 2011, 21, 216–228, doi:10.1590/S0102-695X2011005000079.
[19]
Li, Z. Advances in marine microbial symbionts in the China sea and related pharmaceutical metabolites. Mar. Drugs 2009, 7, 113–129, doi:10.3390/md7020113.
[20]
Cantillo-Ciau, Z.; Moo-Puc, R.; Quijano, L.; Freile-Pelegrín, Y. The tropical brown alga Lobophora variegata: A source of antiprotozoal compounds. Mar. Drugs 2010, 8, 1292–1304.
[21]
Pangestuti, R.; Kim, S.-K. Neuroprotective effects of marine algae. Mar. Drugs 2011, 9, 803–818, doi:10.3390/md9050803.
[22]
Genovese, G.; Tedone, L.; Hamann, M.; Morabito, M. The Mediterranean red alga Asparagopsis: A source of compounds against Leishmania. Mar. Drugs 2009, 7, 361–366, doi:10.3390/md7030361.
[23]
Bradbury, J. Docosahexaenoic acid (DHA): An ancient nutrient for the modern human brain. Nutrients 2011, 3, 529–554, doi:10.3390/nu3050529.
[24]
Dhargalkar, V.K.; Pereira, N. Seaweed: Promising plant of the millennium. Sci. Cult. 2005, 71, 60–66.
[25]
Heo, S.J.; Hwang, J.Y.; Choi, J.I.; Han, J.S.; Kim, H.J.; Jeon, Y.J. Diphlorethohydroxycarmalol isolated from Ishige okamurae, a brown algae, a potent [alpha]-glucosidase and [alpha]-amylase inhibitor, alleviates postprandial hyperglycemia in diabetic mice. Eur. J. Pharmacol. 2009, 615, 252–256.
[26]
El Gamal, A.A. Biological importance of marine algae. Saudi Pharma. J. 2010, 18, 1–25, doi:10.1016/j.jsps.2009.12.001.
[27]
Raven, P.H.; Evert, R.F.; Curtis, H. Biologia Vegetal, 6th ed.; Guanabara Koogan: Rio de Janeiro, Brazil, 2007; p. 906.
[28]
Bold, H.C.; Wynne, M.J. Introduction to the Algae Structure and Reproduction, 2nd ed.; Prentice-Hall Inc.: Englewood Cliffs, NJ, USA, 1985; pp. 1–33.
[29]
Teixeira, V.L.; Kelecom, A.; Gottlieb, O.R. Produtos naturais de algas marinhas. Quím. Nova 1991, 14, 83–90.
[30]
Chatter, R.; Cenac, N.; Roussis, V.; Kharrat, R.; Vergnolle, N. Inhibition of sensory afferents activation and visceral pain by a brominated algal diterpene. Neurogastroenterol. Motil. 2012, 24, e336–e343, doi:10.1111/j.1365-2982.2012.01940.x.
[31]
Chatter, R.; Ben Othman, R.; Rabhi, S.; Kladi, M.; Tarhouni, S.; Vagias, C.; Roussis, V.; Guizani-Tabbane, L.; Kharrat, R. In vivo and in vitro anti-inflammatory activity of neorogioltriol, a new diterpene extracted from the red algae Laurencia glandulifera. Mar. Drugs 2011, 9, 1293–1306, doi:10.3390/md9071293.
[32]
Wiemer, D.F.; Idler, D.D.; Fenical, W. Vidalols A and B, new anti-inflammatory bromophenols from the Caribbean marine red alga Vidalia obtusaloba. Experientia 1991, 47, 851–853.
[33]
Silva, L.M.; Lima, V.; Holanda, M.L.; Pinheiro, P.G.; Rodrigues, J.A.; Lima, M.E.; Benevides, N.M. Antinociceptive and anti-inflammatory activities of lectin from marine red alga Pterocladiella capillacea. Biol. Pharm. Bull. 2010, 33, 830–835, doi:10.1248/bpb.33.830.
[34]
Bitencourt, F.S.; Figueiredo, J.G.; Mota, M.R.; Bezerra, C.C.; Silvestre, P.P.; Vale, M.R.; Nascimento, K.S.; Sampaio, A.H.; Nagano, C.S.; Saker-Sampaio, S.; et al. Antinociceptive and anti-inflammatory effects of a mucin-binding agglutinin isolated from the red marine alga Hypnea cervicornis. Naunyn Schmiedebergs Arch. Pharmacol. 2008, 377, 139–148.
[35]
Neves, S.A.; Freitas, A.L.; Sousa, B.W.; Rocha, M.L.; Correia, M.V.; Sampaio, D.A.; Viana, G.S. Antinociceptive properties in mice of a lectin isolated from the marine alga Amansia multifida Lamouroux. Braz. J. Med. Biol. Res. 2007, 40, 127–134.
[36]
Basbaum, A.I.; Bautista, D.M.; Scherrer, G.; Julius, D. Cellular and molecular mechanisms of pain. Cell 2009, 139, 267–284, doi:10.1016/j.cell.2009.09.028.
[37]
Medzhitov, V.R. Inflammation 2010: New adventures of an old flame. Cell 2010, 140, 771–776, doi:10.1016/j.cell.2010.03.006.
[38]
Tracey, I.; Mantyh, P.W. The cerebral signature for pain perception and its modulation. Neuron 2007, 55, 377–391, doi:10.1016/j.neuron.2007.07.012.
[39]
Hua, S.; Cabot, P.J. Mechanisms of peripheral immunecell-mediated analgesia in inflammation: Clinical and therapeutic implications. Cell 2010, 31, 427–433.
[40]
Gris, P.; Gauthier, J.; Cheng, P.; Gibson, D.G.; Gris, D.; Laur, O.; Pierson, J.; Wentworth, S.; Nackley, A.G.; Maixner, W.; et al. A novel alternatively spliced isoform of the mu-opioid receptor: functional antagonism. Mol. Pain 2010, 6, 33.
Ribeiro, R.A.; Vale, M.L.; Thomazzi, S.M.; Paschoalato, A.B.; Poole, S.; Ferreira, S.H.; Cunha, F.Q. Involvement of resident macrophages and mast cells in the writhing nociceptive response induced by zymosan and acetic acid in mice. Eur. J. Pharmacol. 2000, 387, 111–118, doi:10.1016/S0014-2999(99)00790-6.
[52]
Duarte, I.D.G.; Nakamura, M.; Ferreira, S.H. Participation of the sympathetic system in acetic acid-induced writhing in mice. Braz. J. Med. Biol. Res. 1988, 21, 341–343.
[53]
Ikeda, Y.; Ueno, A.; Naraba, H.; Oh-Ishi, S. Involvement of vanilloid receptor VR1 and prostanoids in the acid-induced writhing responses of mice. Life Sci. 2001, 69, 2911–2919, doi:10.1016/S0024-3205(01)01374-1.
[54]
Hendershot, L.C.; Forsaith, J. Antagonism of the frequency of phenylquinone-induced writhing in the mouse by weak analgesics and nonanalgesics. J. Pharmacol. Exp. Ther. 1959, 125, 237–240.
Pearl, J.; Aceto, M.D.; Harris, L.S. Prevention of writhing and other effects of narcotics and narcotic antagonists in mice. J. Pharmacol. Exp. Ther. 1968, 160, 217–230.
[57]
Loux, J.J.; Smith, S.; Salem, H. Comparative analgesic testing of various compounds in mice using writhing techniques. Arzneim. Forsch. 1978, 28, 1644–1647.
[58]
Kuraishi, Y.; Harada, Y.; Aratani, S.; Satoh, M.; Takagi, H. Involvement of the spinal noradrenergic and serotonergic systems in morphine analgesia: the differences in mechanical and thermal algesic tests. Brain Res. 1983, 273, 245–252, doi:10.1016/0006-8993(83)90849-1.
[59]
Le Bars, D.; Gozariu, M.; Cadden, S.W. Animal models of nociception. Pharmacol. Rev. 2001, 53, 597–652.
[60]
Miranda, F.G.G.; Vilar, J.C.; Alves, I.A.; Cavalcanti, S.C.; Antoniolli, A.R. Antinociceptive and antiedematogenic properties and acute toxicity of Tabebuia avellanedae Lor. ex Griseb. inner bark aqueous extract. BMC Pharmacol. 2001, 1, 1–16.
[61]
El Habazi, K.; Aboufatima, R.; Benharref, A.Z.; Chait, A.; Dalal, A. Study on the antinociceptive effects of Thymus broussonetii Boiss extracts in mice and rats. J. Ethnopharmacol. 2006, 107, 406–411.
[62]
Hunskaar, S.; Hole, K. The formalin test in mice: Dissociation between inflammatory and non-inflammatory pain. Pain 1987, 30, 103–114, doi:10.1016/0304-3959(87)90088-1.
[63]
Tj？lsen, A.; Berge, O.G.; Hunskaar, S.; Rosland, J.H.; Hole, K. The formalin test: An evaluation of the method. Pain 1992, 51, 5–17, doi:10.1016/0304-3959(92)90003-T.
[64]
Granados-Soto, V.; Alonso-Lopez, R.; Asomoza-Espinosa, R.; Rufino, M.O.; Gomes-Lopes, L.D.; Ferreira, S.H. Participation of COX, IL-1β and TNF-α in formalin-induced inflammatory pain. Proceed. Western Pharmacol. Soc. 2001, 44, 15–17.
[65]
Beirith, A.; Santos, A.R.; Calixto, J.B. Mechanisms underlying the nociception and paw oedema caused by injection of glutamate into the mouse paw. Brain Res. 2002, 924, 219–228, doi:10.1016/S0006-8993(01)03240-1.
[66]
Aanonsen, L.M.; Wilcox, G.L. Excitatory amino acid receptors and nociceptive neurotransmission in rat spinal cord. Pain 1990, 41, 309–321, doi:10.1016/0304-3959(90)90008-2.
[67]
Ferreira, J.; Santos, A.R.S.; Calixto, J.B. The role of systemic, spinal and supraspinal L-arginine-nitric oxide-cGMP pathway in thermal hyperalgesia caused by intrathecal injection of glutamate in mice. Neuropharmacology 1999, 38, 835–842, doi:10.1016/S0028-3908(99)00006-4.
[68]
Mao, J.; Price, D.D.; Hayes, R.L.; Lu, J.; Mayer, D.J. Differential roles of NMDA and non-NMDA receptor activation in induction and maintenance of thermal hyperalgesia in rats with painful peripheral mononeuropathy. Brain Res. 1992, 598, 271–278, doi:10.1016/0006-8993(92)90193-D.
[69]
Sato, M.; Sano, H.; Iwaki, D.; Kudo, K.; Konishi, M.; Takahashi, H.; Takahashi, T.; Imaizumi, H.; Asai, Y.; Kuroki, Y. Direct binding of toll-like receptor 2 to zymosan, and zymosan-induced NF-κB activation and TNF-α secretion are down-regulated by lung collectin surfactant protein A. J. Immunol. 2003, 171, 417–425.
[70]
Daum, T.; Rohrbach, M.S. Zymosan induces selective release of arachidonic acid from rabbit alveolar macrophages via stimulation of a β-glucan receptor. FEBS Lett. 1992, 309, 119–122, doi:10.1016/0014-5793(92)81077-Y.
[71]
Noble, P.W.; Henson, P.M.; Lucas, C.; Mora-Worms, M.; Carre, P.C.; Riches, D.W.H. Transforming growth factor-β primes macrophages to express inflammatory gene products in response to particulate stimuli by an autocrine/paracrine mechanism. J. Immunol. 1993, 151, 979–989.
[72]
Okazaki, M.; Chiba, N.; Adachi, Y.; Ohno, N.; Yadomae, T. Signal transduction pathway on-glucans-triggered hydrogen peroxide production by murine peritoneal macrophages in vitro. Biol. Pharm. Bull. 1996, 19, 18–23, doi:10.1248/bpb.19.18.
[73]
Hsieh, G.C.; Chandran, P.; Salyers, A.K.; Pai, M.; Zhu, C.Z.; Wensink, E.J.; Witte, D.G.; Miller, T.R.; Mikusa, J.P.; Baker, S.J.; et al. H4 receptor antagonism exhibits anti-nociceptive effects in inflammatory and neuropathic pain models in rats. Pharmacol. Biochem. Behav. 2010, 95, 41–50.
[74]
Strakhova, M.I.; Cuff, C.A.; Manelli, A.M.; Carr, T.L.; Witte, D.G.; Baranowski, J.L.; Vortherms, T.A.; Miller, T.R.; Rundell, L.; McPherson, M.J.; et al. In vitro and in vivo characterization of A-940894: A potent histamine H4 receptor antagonist with anti-inflammatory properties. Br. J. Pharmacol. 2009, 157, 44–54.
[75]
Bitencourt, M.A.O.; Dantas, G.R.; Lira, D.P.; Barbosa-Filho, J.M.; Miranda, G.E.C.; Santos, B.V.O.; Souto, J.T. Aqueous and methanolic extracts of Caulerpa mexicana suppress the cell migration and ear edema induced by inflammatory agents. Mar. Drugs 2011, 9, 1332–1345, doi:10.3390/md9081332.
[76]
Vidal, A.; Fallarero, A.; Andrade-Wartha, E.R.S.; Silva, A.M.O.; Lima, A.; Torres, R.P.; Vuorela, P.; Mancini-Filho, J. Composición química y actividad antioxidante del alga marina roja Bryothamnion triquetrum (S.G.Gmelin) Howe. Rev. Bras. Cienc. Farm. 2006, 42, 509–600.
[77]
Zubia, M.; Robledo, D.; Freile-Pelegrin, Y. Antioxidant activities in tropical marine macroalgae from the Yucatan Peninsula, Mexico. J. Appl. Phycol. 2007, 19, 449–458, doi:10.1007/s10811-006-9152-5.
[78]
Fallarero, A.; Loikkanen, J.J.; Mansito, P.T.; Casta？eda, O.; Vidal, A. Effects of aqueous extracts of Halimeda incrassata (Ellis) Lamouroux and Bryothamnion triquetrum (S.G. Gmelin) Howe on hydrogen peroxide and methyl mercury-induced oxidative stress in GT1-7 mouse hypothalamic immortalized cells. Phytomedicine 2003, 10, 39–47, doi:10.1078/094471103321648647.
[79]
Maia, R.M.; Moura, C.W.N.; Bispo, V.S.; Santos, J.L.A.; Santana, R.S.; Matos, H.R. Avalia？？o do sequestro do óxido nítrico (NO) pelo extrato metanólico da alga Bryothamnion triquetrum (Gmelin) Howe. Rev. Bras. Farmacogn. 2010, 20, 489–493.
Wang, Z.Q.; Porreca, F.; Cuzzocrea, S.; Galen, K.; Lightfoot, R.; Masini, E.; Muscoli, C.; Mollace, V.; Ndengele, M.; Ischiropoulos, H.; et al. A newly identified role for superoxide in inflammatory pain. J. Pharmacol. Exp. Ther. 2004, 309, 869–878, doi:10.1124/jpet.103.064154.
[82]
Hacimuftuoglu, A.; Handy, C.R.; Goettl, V.M.; Lin, C.G.; Dane, S.; Stephens, R.L., Jr. Antioxidants attenuate multiple phases of formalin-induced nociceptive response in mice. Behav. Brain Res. 2006, 173, 211–216.
[83]
Viana, G.S.B.; Freitas, A.L.P.; Lima, M.M.L.; Vieira, L.A.P.; Andrade, M.C.H.; Benevides, N.M.B. 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. 2002, 35, 713–722.
[84]
Vieira, L.A.P.; Freitas, A.L.P.; Feitosa, J.P.A.; Silva, D.C.; Viana, G.S.B. The alga Bryothamnion seaforthii contains carbohydrates with antinociceptive activity. Braz. J. Med. Biol. Res. 2004, 37, 1071–1079, doi:10.1590/S0100-879X2004000700017.
[85]
Romay, Ch.; González, R.; Ledón, N.; Remirez, D.; Rimbau, V. C-phycocyanin: A biliprotein with antioxidant, anti-inflammatory and neuroprotective effects. Curr. Protein Pept. Sci. 2003, 4, 207–216, doi:10.2174/1389203033487216.
Species Link. Available online: http://www.specieslink.com (accessed on 20 June 2012).
[88]
Almeida, R.N.; Falc？o, A.C.G.M.; Diniz, R.S.T.; Quintanas-Júnior, L.J.; Polari, R.M.; Barbosa-Filho, J.M.; Agra, M.F.; Duarte, J.C.; Ferreira, C.D.; Antoniolli, A.R.; Araújo, C.C. Metodologia para avalia？？o de plantas com atividade no Sistema Nervoso Central e alguns dados experimentais. Rev. Bras. Farm. 1999, 80, 72–76.
[89]
Collier, H.O.J.; Dinneen, L.C.; Johnson, C.A.; Schneider, C. The abdominal constriction response and its suppression by analgesic drugs in mice. Br. J. Pharmacol. 1968, 32, 285–310.
[90]
Doherty, N.X.; Poubelle, P.; Borgeat, P.; Beave, T.H.; Westrich, G.L.; Schrader, N.L. Intraperitoneal injection of zymosan in mice induces pain, inflammation and the synthesis of peptidoleukotrienes and prostaglandin E2. Prostaglandins 1985, 30, 769–789, doi:10.1016/0090-6980(85)90006-1.
