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Planta Med 2012; 78(14): 1543-1548
DOI: 10.1055/s-0032-1315026
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Antinociceptive Effects of a Chloroform Extract and the Alkaloid Dicentrine Isolated from Fruits of Ocotea puberula

Deise Prehs Montrucchio
1   Departamento de Farmácia, Setor de Ciências da Saúde, Universidade Federal do Paraná, Curitiba, PR, Brazil
2   Programa de Pós-Graduação em Farmacologia, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil
,
Obdulio Gomes Miguel
1   Departamento de Farmácia, Setor de Ciências da Saúde, Universidade Federal do Paraná, Curitiba, PR, Brazil
,
Sandra Maria Warumby Zanin
1   Departamento de Farmácia, Setor de Ciências da Saúde, Universidade Federal do Paraná, Curitiba, PR, Brazil
,
Gabriel Araujo da Silva
3   Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil
,
Alcíbia Maia Cardozo
4   Departamento de Patologia, Centro de Ciências da Saúde, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil
,
Adair Roberto Soares Santos
2   Programa de Pós-Graduação em Farmacologia, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil
5   Laboratório de Neurobiologia da Dor e Inflamação, Departamento de Ciências Fisiológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil
› Author Affiliations
Further Information

Publication History

received 07 May 2012
revised 05 June 2012

accepted 08 June 2012

Publication Date:
16 July 2012 (online)

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Abstract

The present work describes the chemical characterization of a chloroform fraction (CF) obtained from an extract of Ocotea puberula (Lauraceae) fruits, and preliminary antinociceptive analysis of CF and the alkaloid dicentrine, isolated from this fraction. CF (30–300 mg/kg, p. o.) caused dose-related inhibition of abdominal constrictions caused by acetic acid and also inhibited both phases of formalin-induced nociception. However, hexane or ethyl acetate fractions did not produce any effect. Antinociception caused by CF (100 mg/kg, p. o.) in the acetic acid test was not affected either by caffeine, an adenosine receptor antagonist, or by naloxone, an opioid receptor antagonist, and neither was associated with nonspecific effects such as muscle relaxation or sedation. Furthermore, dicentrine (30–300 mg/kg, p. o.) produced dose-related inhibition of acetic acid-induced pain without causing changes in the motor performance of mice. The results show, for the first time, that CF from Ocotea puberula fruits produced marked antinociception in different models of chemical pain, and this effect appears to be, at least in part, due to the presence of dicentrine. The mechanism by which CF and the alkaloid produced antinociception still remains unclear, but the adenosinergic or opioid system seems unlikely to be involved in this action.

Key words

Ocotea puberula - Lauraceae - alkaloid - dicentrine - antinociception

Supporting Information

 

  • References

  • 1 Araujo AJ. Estudo fitoquímico das folhas de Ocotea puberula (Reich.) Nees (Lauraceae) [dissertation]. Curitiba: Universidade Federal do Paraná; 2000
    PubMedGoogle Scholar
  • 2 Farago PV. Estudo morfo-anatômico e fitoquímico de Ocotea puberula (Rich.) Nees, família Lauraceae, da região dos campos gerais, Ponta Grossa, Paraná [dissertation]. Curitiba: Universidade Federal do Paraná; 2002
    PubMedGoogle Scholar
  • 3 Jacobucci GA. Ocoteine, the alkaloid separated from the bark of Ocotea puberula . J Argentine Chem Soc 1954; 42: 18-29
    PubMedGoogle Scholar
  • 4 Baralle F, Schvarzberg N, Vernengo M, Comim J. Dehydroocoteine and didehydroocoteine from Ocotea puberula . Experientia 1972; 28: 875-876
    CrossrefPubMedGoogle Scholar
  • 5 Baralle F, Schvarzberg N, Vernengo M, Moltrasio GY, Giacopello D. Thalicminine from Ocotea puberula . Phytochemistry 1973; 12: 948-949
    CrossrefPubMedGoogle Scholar
  • 6 Zanin SMW, Lordello ALL. Aporphine alkaloids in Ocotea species (Lauraceae). Quim Nova 2007; 30: 92-98
    PubMedGoogle Scholar
  • 7 Zanin SMW, Miguel OG, Montrucchio DP, Costa CK, Lagos JB, Lordello ALL. Seedlings of Ocotea puberula (Lauraceae): identification and monitorizing of aporphinoid alkaloids. Quim Nova 2011; 34: 743-747
    PubMedGoogle Scholar
  • 8 Kondo Y, Imai Y, Hojo H, Endo T, Nozoe S. Suppression of tumor cell growth and mitogen response by aporphine alkaloids, dicentrine, glaucine, corydine, and apomorphine. J Pharmacobiodyn 1990; 13: 426-431
    CrossrefPubMedGoogle Scholar
  • 9 Huang RL, Chen CC, Huang YL. Anti-tumor effects of d-dicentrine from the root of Lindera megaphylla . Planta Med 1998; 64: 212-215
    Article in Thieme ConnectPubMedGoogle Scholar
  • 10 Stévigny C, Bailly C, Quetin-Leclercq J. Cytotoxic and antitumor potentialities of aporphinoid alkaloids. Curr Med Chem Anticancer Agents 2005; 5: 173-182
    CrossrefPubMedGoogle Scholar
  • 11 Konkimalla VB, Efferth T. Inhibition of epidermal growth factor receptor over-expressing cancer cells by the aphorphine-type isoquinoline alkaloid, dicentrine. Biochem Pharmacol 2010; 79: 1092-1099
    CrossrefPubMedGoogle Scholar
  • 12 Yu SM, Hsu SY, Ko FN, Chen CC, Huang YL, Huang TF, Teng CM. Haemodynamic effects of dicentrine, a novel α1-adrenoceptor antagonist: comparison with prazosin in spontaneously hypertensive and normotensive Wistar-Kyoto rats. Br J Pharmacol 1992; 106: 797-801
    CrossrefPubMedGoogle Scholar
  • 13 Chen KS, Wu YC, Wu TS. Bioactive alkaloids from Illigera luzonensis . J Nat Prod 1997; 60: 645-647
    CrossrefPubMedGoogle Scholar
  • 14 Teng CM, Yu SM, Ko FN, Chen CC, Huang YL, Huang TF. Dicentrine, a natural vascular α1-adrenoceptor antagonist, isolated from Lindera megaphylla . Br J Pharmacol 1991; 104: 651-656
    CrossrefPubMedGoogle Scholar
  • 15 Yu SM, Kang YF, Chen CC, Teng CM. Effects of dicentrine on haemodynamic, plasma lipid, lipoprotein level and vascular reactivity in hyperlipidaemic rats. Br J Pharmacol 1993; 108: 1055-1061
    CrossrefPubMedGoogle Scholar
  • 16 Tsai TH, Wang GJ, Lin LC. Vasorelaxing alkaloids and flavonoids from Cassytha filiformis . J Nat Prod 2008; 71: 289-291
    CrossrefPubMedGoogle Scholar
  • 17 Marquesini NR. Plantas usadas como medicinais pelos índios do Paraná e Santa Catarina, sul do Brasil – Guarani, Kaigang, Xogleng, Ava-Guarani, Kraô e Cayuá [dissertation]. Curitiba: Universidade Federal do Paraná; 1995
    PubMedGoogle Scholar
  • 18 Santos ARS, Beirith A, Calixto JB, Hess SC, Messana I, Ferrari F, Yunes RA. Study of the antinociceptive action of the ethanolic extract and the triterpene 24-hydroxytormentic acid isolated from the stem bark of Ocotea suaveolens . Planta Med 1999; 65: 50-55
    Article in Thieme ConnectPubMedGoogle Scholar
  • 19 Zschocke S, Drewes SE, Paulus K, Bauer R, Staden J. Analytical and pharmacological investigation of Ocotea bullata (black stinkwood) bark and leaves. J Ethnopharmacol 2000; 71: 219-230
    CrossrefPubMedGoogle Scholar
  • 20 Souza LA, Moscheta IS. Morphology and anatomy of the fruit development of Ocotea puberula (Rich.) Nees and Nectandra megapotamica (Spreng.) Mez (Lauraceae). Acta Cientif Venez 2000; 51: 84-89
    PubMedGoogle Scholar
  • 21 Carvalho JLS, Cunico MM, Dias JFG, Miguel MD, Miguel OG. Term-stability of extractive processes from Nasturtium officinale R. Br. Brassicaceae for Soxhlet modified system. Quim Nova 2009; 32: 1031-1035
    CrossrefPubMedGoogle Scholar
  • 22 Zimmermann M. Ethical guidelines for investigations of experimental pain in conscious animals. Pain 1983; 16: 109-110
    CrossrefPubMedGoogle Scholar
  • 23 Nascimento FP, Figueredo SM, Marcon R, Martins DF, Macedo-Junior SJ, Lima DAN, Almeida RC, Ostroski RM, Rodrigues ALS, Santos ARS. Inosine reduces pain-related behavior in mice: involvement of adenosine A1 and A2A receptor subtypes and protein kinase C pathways. J Pharmacol Exp Ther 2010; 334: 590-598
    CrossrefPubMedGoogle Scholar
  • 24 Campos ROP, Santos ARS, Vaz ZR, Pinheiro TR, Pizzolatti MG, Cechinel Filho V, Monache FD, Yunes RA, Calixto JB. Antinociceptive properties of the hydroalcoholic extract and preliminary study of a xanthone isolated from Polygala cyparissias (Polygalaceae). Life Sci 1997; 61: 1619-1630
    CrossrefPubMedGoogle Scholar
  • 25 Luiz AP, Moura JD, Meotti FC, Guginski G, Guimarães CLS, Azevedo MS, Rodrigues ALS, Santos ARS. Antinociceptive action of ethanolic extract obtained from roots of Humirianthera ampla Miers. J Ethnopharmacol 2007; 114: 355-363
    CrossrefPubMedGoogle Scholar
  • 26 Rodrigues AL, da Silva GL, Mateussi AS, Fernandes ES, Miguel OG, Yunes RA, Calixto JB, Santos ARS. Involvement of monoaminergic system in the antidepressant-like effect of the hydroalcoholic extract of Siphocampylus verticillatus . Life Sci 2002; 70: 1347-1358
    CrossrefPubMedGoogle Scholar
  • 27 Hirano E, Possamai E. Fruit maturity state and seed germination of three species of Lauraceae. Scientia Agraria 2008; 9: 219-223
    PubMedGoogle Scholar
  • 28 Vaz ZR, Cechinel Filho V, Yunes RA, Calixto JB. Antinociceptive action of 2-(4-bromobenzoyI)-3-methyI-4,6-dimethoxy benzofuran, a novel xanthoxyline derivative on chemical and thermal models of nociception in mice. J Pharmacol Exp Ther 1996; 278: 304-312
    PubMedGoogle Scholar
  • 29 Coy Barrera ED, Cuca Suárez LE. In vitro inhibitory activities of Lauraceae aporphine alkaloids. Nat Prod Commun 2010; 5: 383-386
    PubMedGoogle Scholar
  • 30 Coy ED, Cuca LE, Sefkow M. COX, LOX and platelet aggregation inhibitory properties of Lauraceae neolignans. Bioorg Med Chem Lett 2009; 19: 6922-6925
    CrossrefPubMedGoogle Scholar
  • 31 Ballabeni V, Tognolini M, Giorgio C, Bertoni S, Bruni R, Barocelli E. Ocotea quixos Lam. essential oil: in vitro and in vivo investigation on its anti-inflammatory properties. Fitoterapia 2010; 81: 289-295
    CrossrefPubMedGoogle Scholar
  • 32 Tsai TH, Tsai TR, Chou CJ, Chen CF. Determination of dicentrine in rat plasma by high-performance liquid chromatography and its application to pharmacokinetics. J Chromatogr B 1996; 681: 277-281
    PubMedGoogle Scholar
  • 33 Lai YC, Kuo TF, Chen CK, Tsai HJ, Lee SS. Metabolism of dicentrine: identification of phase I and phase II metabolites in miniature pig urine. Drug Metab Dispos 2010; 38: 1714-1722
    CrossrefPubMedGoogle Scholar
  • 34 Conserva LM, Pereira CAB, Barbosa-Filho JM. Alkaloids of the Hernandiaceae: occurrence and a compilation of their biological activities. Alkaloids Chem Biol 2005; 62: 175-243
    PubMedGoogle Scholar