Inflammation

, Volume 40, Issue 6, pp 2118–2128 | Cite as

Milonine, an Alkaloid of Cissampelos sympodialis Eichl. (Menispermaceae) Inhibits Histamine Release of Activated Mast Cells

  • Adriano Francisco Alves
  • Giciane Carvalho Vieira
  • Francisco Allysson A. F. Gadelha
  • Luiz Henrique Agra Cavalcante-Silva
  • Marco Aurélio Martins
  • José Maria Barbosa-Filho
  • Marcia Regina Piuvezam
ORIGINAL ARTICLE
First Online:

Abstract

Milonine is an alkaloid of Cissampelos sympodialis Eichl. (Menispermaceae), a plant used in the northeast of Brazil to treat allergies such as asthma, rhinitis, and other conditions. Previously, several alkaloids were isolated from its roots and leaves with pharmacological properties in asthma and acute inflammation models. Therefore, the aim of this study was to evaluate the milonine effect on mast cells degranulation in vivo and in vitro. Swiss mice (n = 8) were used in models of paw edema induced by carrageenan, compound 48/80, or histamine. One hour before challenge, the animals were treated with milonine (at different doses) or standard drugs and, at different time points, the edema formation was measured. In addition, other different methods, such as anaphylactic shock reaction and scratching behavior models both induced by compound 48/80, a mast cell degranulator, were used to assess milonine effect histamine release in vivo. Moreover, milonine effect on mast cell degranulation in vitro was also carried out. Firstly, it was observed that milonine significantly decreased the carrageenan edema formation only at the beginning of the reaction (i.e., up to 2 h after challenge). Furthermore, this alkaloid decreased the edema induced by compound 48/80, maintained the paw tissue integrity, without modulating histamine-induced paw edema. In anaphylactic shock reaction, milonine increased the time of animal survival when compared with compound 48/80 group. Milonine also significantly decreased the scratching behavior induced by compound 48/80 with decreasing of mast cell degranulation in vitro. Therefore, these data indicated that milonine presents anti-allergic properties by decreasing mast cell degranulation rather than acting on histamine effect.

KEY WORDS

milonine mast cell degranulation histamine alkaloid Cissampelos sympodialis Eichl. (Menispermaceae) 
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Notes

Funding

This work was supported by “INCT para Controle do Câncer.”

Compliance with Ethical Standards

Conflict of Interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

References

  1. 1.
    Martins, E.R., D.M. Castro, D.C. Castellani, and J.E. Dias. 1995. Plantas medicinais. Viçosa: UFV. 220p.Google Scholar
  2. 2.
    Simões, C.M.O., E.P. Schenkel, G. Gosmann, J.C.P. Mello, L.A. Mentz, and P.R. Petrvick. 2003. Farmacognosia: da planta ao medicamento. Porto Alegre/Florianópolis, 5. ed., Editora da UFRGS/Editora da UFSC.Google Scholar
  3. 3.
    Chang, H.-C., F.-R. Chang, Y.-C. Wu, and Y.-H. Lai. 2004. Anti-cancer effect of liriodenine on human lung cancer cells. The Kaohsiung Journal of Medical Sciences 20 (8).Google Scholar
  4. 4.
    Cahen, Raymond L., and Kristen Tvede. 1952. Homatropine methylbromide: a pharmagological reevaluation. Journal of Pharmacology and Experimental Therapeutics 105 (2): 166–177.PubMedGoogle Scholar
  5. 5.
    Brainer-Lima, P.T. 1997. Opióides e receptors de membrane cellular. Revisão atualizada. Neurobiologia 4: 149–158.Google Scholar
  6. 6.
    Lima, T.F.A., J.D.B. Rocha, A.B. Guimarães-Costa, J.M. Barbosa-Filho, D. Decoté-Ricardo, E.M. Saraiva, L.B. Arruda, M.R. Piuvezam, and L.M.T. Peçanha. 2014. Warifteine, an alkaloid purified from Cissampelos sympodialis, inhibits neutrophil migration in vitro and in vivo. Journal of Immunology Research.Google Scholar
  7. 7.
    Leite, F.C. 2014. Curine, an alkaloid isolated from Chondrodendron platyphyllum inhibits prostaglandin E2 in experimental models of inflammation and pain. Planta Medica 80: 1072–1078.CrossRefPubMedGoogle Scholar
  8. 8.
    De Freitas, M.B., J.L. De Aelncar, E.V.L. Da-Cunha, J.M. Barbosa-Filho, and A.I. Gray. 1995. Milonine, an 8,14-dihydromorphinandienone alkaloid from leaves of Cissampelos sympodialis. Phytochemikstry 40: 1553–1555.CrossRefGoogle Scholar
  9. 9.
    Correia, M. 1984. Dicionario de Plantas úteis do Brasil e exóticas cultivadas. (Dictionary of Brazilian useful plants and exotic cultivated). Ministerio da Agricultura.Google Scholar
  10. 10.
    Marinho, A. F., Barbosa-Filho, J. M., Oliveira, E. J. A validated method for the simultaneous quantitation of bioactive alkaloid markers in the leaf ethanolic extract of Cissampelos sympodialis Eichl.: a phenological variation study. Phytochemical Analysis. 23, p. 426–432, 2012.Google Scholar
  11. 11.
    De Lira, G.A., et al. 2002. Roraimine: a bisbenzylisoquinoline alkaloid from Cissampelos sympodialis roots. Fitoterapia 73: 356–358.CrossRefPubMedGoogle Scholar
  12. 12.
    Bezerra-Santos, C.R., et al. 2006. Anti-allergic properties of Cissampelos sympodialis and its isolated alkaloid warifteine. International Immunopharmacology 6: 1152–1160.CrossRefPubMedGoogle Scholar
  13. 13.
    Costa, H.F., et al. 2008. Warifteine, a bisbenzylisoquinoline alkaloid, decreases immediate allergic and thermal hyperalgesic reactions in sensitized animals. International Immunopharmacology 8: 519–525.CrossRefPubMedGoogle Scholar
  14. 14.
    Rocha, J.D., et al. 2010. Inhibitory effect of the alkaloid warifteine purified from Cissampelos sympodialis on B lymphocyte function in vitro and in vivo. Planta Medica 76: 325–330.CrossRefPubMedGoogle Scholar
  15. 15.
    Vieira, G.C., J.F. De Lima, R.C.B.Q. De Figueiredo, S.R. Mascarenhas, C.R.E. Bezerra-Santos, and M.R. Piuvezam. 2013. Inhaled Cissampelos sympodialis down-regulates airway allergic reaction by reducing lung CD3+T cells. Phytotherapy Research 27: 916–925.CrossRefPubMedGoogle Scholar
  16. 16.
    Costa, H.F., F.C. Leite, A.F. Alves, J.M. Barbosa-Filho, C.R. Bezerra Dos Santos, and M.R. Piuvezam. 2013. Managing murine food allergy with Cissampelos sympodialis Eichl (Menispermaceae) and its alkaloids. International Immunopharmacology 17: 300–308.CrossRefPubMedGoogle Scholar
  17. 17.
    Cavalcante, H.M.M., T.P. Ribeiro, D.F. Silva, X.P. Nunes, J.M. Barbosa-Filho, M.F.F.M. Diniz, N.A. Correia, V.A. Braga, and I.A. Medeiros. 2011. Cardiovascular effects elicited by Milonine, a new 8,14 Dihydromorphinandienone alkaloid. Basic & Clinical Pharmacology & Toxicology 108: 122–130.CrossRefGoogle Scholar
  18. 18.
    Sherwin, C.M., I.J. Christiansen, H.W.E. Duncan, D.C. Lay, J.A. Mench, C.E. O’Connor, and J.C. Petheric. 2003. Guidelines for the ethical use of animals in applied ethology studies. Applied Animal Behaviour Science 8: 291–305.CrossRefGoogle Scholar
  19. 19.
    Henriques, M.G.M.O. P.M.R. Silva, M.A. Martins, C.A. Flores, F.Q. Cunha, J. Assreuyfilho, & R.S.B. Cordeiro. 1987. Mouse paw oedema. A new model for inflammation?. Brazilian Journal of Medical and Biological Research 20:243–249.Google Scholar
  20. 20.
    Naidu, P.S., S.G. Kinsey, T.L. Guo, et al. 2010. Regulation of inflammatory pain by inhibition of fatty acid amide hydrolase. The Journal of Pharmacology and Experimental Therapeutics 334 (1): 182–190.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Zou, Y., C. Dong, M. Yuan, G. Gao, S. Wang, X. Liu, H. Han, and Bo Li. 2014. Instilled air promotes lipopolysaccharide-induced acute lung injury. Experimental and Therapeutic Medicine 7: 816–820.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Németh, A., and P. Röhlich. 1980. Rapid separation of rat peritoneal mast cells with Percoll. European Journal of Cell Biology 20 (3): 272–275.PubMedGoogle Scholar
  23. 23.
    Murray, A.R., E. Kisin, S.S. Leonard, S.H. Young, C. Kommineni, V.E. Kagan, V. Castranova, and A.A. Shvedova. 2009. Oxidative stress and inflammatory response in dermal toxicity of single-walled carbon nanotubes. Toxicology 257 (3): 161–171.CrossRefPubMedGoogle Scholar
  24. 24.
    Torres, R.C., M.M. Batista, A.H. Pons, A.R. Silva, R.S.B. Cordeiro, M.A. Martins, P.M.R. Silva, and V.F. Carvalho. 2012. Activation of PPARg by restores mast cell numbers and reactivity in alloxan-diabetic rats by reducing the systemic glucocorticoid levels. European Journal of Pharmacology 691: 261–267.CrossRefPubMedGoogle Scholar
  25. 25.
    Shore, P.A., A. Burkhalter, and V.H. Cohn Jr. 1959. A method for the fluorometric assay of histamine in tissues. The Journal of Pharmacology and Experimental Therapeutics 127: 182–186.PubMedGoogle Scholar
  26. 26.
    Inagaki, N., K. Igeta, J.F. Kim, M. Nagao, N. Shiraishi, N. Nakamura, and H. Nagai. 2002. Involvement of unique mechanisms in the induction of scratching behavior in BALB/c mice by compound 48/80. European Journal of Pharmacology 448: 175–183.CrossRefPubMedGoogle Scholar
  27. 27.
    Cerqueira-Lima, A.T., N.M. Alcântara-Neves, L.C.P. Carvalho, R.S. Costa, J.M. Barbosa-Filho, and M.R. Piuvezam. 2010. Effects of Cissampelos sympodialis Eichl. and its alkaloid, Warifteine, in an experimental model of respiratory allergy to Blomia tropicalis. Curr DrugTargets 11: 1458–1467.Google Scholar
  28. 28.
    Scrivo, R., M. Vasile, I. Bartosiewicz, and G. Valesini. 2011. Inflammation as “common soil” of the multifactorial diseases. Autoimmunity Reviews 10: 369–374.CrossRefPubMedGoogle Scholar
  29. 29.
    Posadas, I., M. Bucci, F. Roviezzo, et al. 2004. Carrageenan-induced mouse paw oedema is biphasic, age-weight dependent and displays differential nitric oxide cyclooxygenase-2 expression. British Journal of Pharmacology 142 (2): 331–338.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Kanaan, S.A., B. Safieh-Garabedian, J.J. Haddad, et al. 1997. Effects of various analgesic and anti-inflammatory drugs on endotoxin-induced hyperalgesia in rats and mice. Pharmacology 54 (6): 285–297.CrossRefPubMedGoogle Scholar
  31. 31.
    Palomaki, V.A.B., and J.T. Laitinen. 2006. The basic secretagogue compound 48/80 activates G proteins indirectly via stimulation of phospholipase D–lysophosphatidic acid receptor axis and 5-HT1A receptors in rat brain sections. British Journal of Pharmacology 147: 596–606.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Paton, W.D.M. 1951. Compound 48/80: a potent histamine liberator. British Journal of Pharmacology 6: 499–508.Google Scholar
  33. 33.
    Niemegeers, C.J., F. Awouters, V. Nueten, S. De Nollin, and P.A. Janssen. 1978. Protection of rats from compound 48/80-induced lethality. A simple test for inhibitors of mast cell-mediated shock. Archives Internacionales of Pharmacodynamie et de therapie 234: 164–176.Google Scholar
  34. 34.
    Bronner, C., C. Wiggins, D. Monté, F. Märki, A. Capron, Y. Landry, and R.C. Franson. 1987. Compound 48/80 is a potent inhibitor of phospholipase C and a dual modulator of phospholipase A2 from human platelet. Biochimica et Biophysica Acta 15: 301–305.CrossRefGoogle Scholar
  35. 35.
    Hashimoto, T., H. Ohata, K. Momose, and K. Honda. 2005. Lysophosphatidic acid induces histamine release from mast cells and skin fragments. Pharmacology 75: 13–20.CrossRefPubMedGoogle Scholar
  36. 36.
    Tatemoto, K., Y. Nozaki, R. Tsuda, S. Konno, K. Tomura, M. Furuno, H. Ogasawara, K. Edamura, H. Takagi, H. Iwamura, M. Noguchi, and T. Naito. 2006. Immunoglobulin E independent activation of mast cell is mediated by Mrg receptors. Biochemical and Biophysical Research Communications 349: 1322–1328.CrossRefPubMedGoogle Scholar
  37. 37.
    Gomes, J.C., L.C. Di Stasi, F. Sgarbosa, and L.E.S. Barata. 1994. Pharmacological evaluation of the inhibitory effect of extracts from Anchieta salutaris on the histamine release induced in the rat and the guinea pig. Allergy Immunology 103: 1888–1193.CrossRefGoogle Scholar
  38. 38.
    Kemp, S.F., and R.F. Lockey. 2002. Anaphylaxis: a review of causes and mechanisms. Journal of Allergy and Clinical Immunology 110: 341–348.CrossRefPubMedGoogle Scholar
  39. 39.
    Ribeiro-Filho, J., F.C. Leite, H.F. Costa, A.S. Calheiros, R.C. Torres, C.T. Azevedo, M.A. Martins, CDa S. Dias, P.T. Bozza, and M.R. Piuvezam. 2014. Curine inhibits mast cell-dependent responses in mice. Journal of Ethnopharmacology 155: 1118–1124.Google Scholar
  40. 40.
    Wang, D., J. Zhu, S. Wang, et al. 2011. Antitussive, expectorant and anti-inflammatory alkaloids from Bulbus Fritillariae Cirrhosae. Fitoterapia 82 (8): 1290–1294.CrossRefPubMedGoogle Scholar
  41. 41.
    Gillespie, E., R.J. Levine, and S.C. Malawista. 1968. Histamine release from rat peritoneal mast cells, inhibition by colchicine and potentiation by deuterium oxide. The Journal of Pharmacology and Experimental Therapeutics 164: 163–165.Google Scholar
  42. 42.
    Chatterjea, D., and T. Martinov. 2015. Mast cells: versatile gatekeepers of pain. Molecular Immunology 63: 38–44.CrossRefPubMedGoogle Scholar
  43. 43.
    Ghosal, S., A. Shanthy, M. Mukhopadhyay, M.K. Sarkar, and P.K. Das. 1986. Effect of lycoriside, an acylglucosyloxy alkaloid, on mast cells. Pharmaceutical Research 3 (4): 240–243.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Adriano Francisco Alves
    • 1
  • Giciane Carvalho Vieira
    • 1
  • Francisco Allysson A. F. Gadelha
    • 1
  • Luiz Henrique Agra Cavalcante-Silva
    • 1
    • 2
  • Marco Aurélio Martins
    • 3
  • José Maria Barbosa-Filho
    • 2
  • Marcia Regina Piuvezam
    • 1
    • 2
  1. 1.Laboratory of Immunopharmacology, Health Sciences CentreFederal University of ParaíbaJoão PessoaBrazil
  2. 2.Postgraduate Program in Natural Products and Bioactive Synthetics (PgPNSB), Health Sciences CentreFederal University of ParaíbaJoão PessoaBrazil
  3. 3.Laboratory of Inflammation, Oswaldo Cruz Institute, FIOCRUZRio de JaneiroBrazil

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