Download PDF
Planta Med 2010; 76(13): 1419-1423
DOI: 10.1055/s-0029-1240942
Pharmacology
Original Papers
© Georg Thieme Verlag KG Stuttgart · New York

The Antinociceptive Effect of a Benzopyran (HP1) Isolated from Hypericum polyanthemum in Mice Hot-Plate Test is Blocked by Naloxone

Juliana Schulte Haas1 [*] , Alice Fialho Viana1 [*] , Ana Paula Machado Heckler1 , Gilsane Lino von Poser1 , Stela Maris Kuze Rates1
  • 1Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
Further Information

Publication History

received October 8, 2009 revised Dec. 23, 2009

accepted February 3, 2010

Publication Date:
22 March 2010 (online)

Also available at
    Permissions and Reprints

Abstract

Several species of the genus Hypericum (Guttiferae) have been used for analgesic purposes all over the world and some of them have demonstrated to possess this effect in rodents. This study describes the antinociceptive effect of the cyclohexane extract from aerial parts of H. polyanthemum (POL) as well as of benzopyrans, 6-isobutyryl-5,7-dimethoxy-2,2-dimethyl-benzopyran (HP1), 7-hydroxy-6-isobutyryl-5-methoxy-2,2-dimethyl-benzopyran (HP2), and 5-hydroxy-6-isobutyryl-7-methoxy-2,2-dimethyl-benzopyran (HP3), which are the main components of POL. The antinociceptive effect was evaluated through hot-plate and writhing tests in mice, and the opioid system involvement was assessed by using naloxone (2.5 mg/kg, s. c.) antagonism. In the hot-plate test, POL (45, 90, 180 mg/kg, p.o) showed a dose-dependent effect, and out of the benzopyrans only HP1 (30, 60, 90 mg/kg, i. p.) was active. Its effect was also dose-dependent, with the maximum reached at 60 mg/kg. HP1 60 mg/kg (p. o.) also inhibited acetic acid-induced writhing in 58 %. The pretreatment with naloxone abolished the antinociceptive effect of HP1 60 mg/kg (i.p) in the hot plate. Furthermore, the H. polyanthemum cyclohexane extract and HP1 did not affect the mice performance in the rota-rod apparatus suggesting that at antinociceptive doses they do not present gross neurotoxicity nor induce motor impairment. From these data it is reasonable to assume that the benzopyran HP1 accounts for the H. polyanthemum cyclohexane extract antinociceptive effect, and this effect is, at least in part, mediated by an opioid-like mechanism.

Key words

Hypericum polyanthemum - Guttiferae - benzopyrans - antinociceptive effect

References

  • 1 Mendes F R, Mattei R, Carlini E L A. Activity of Hypericum brasiliense and Hypericum cordatum on the central nervous system in rodents.  Fitoterapia. 2002;  73 462-471
    CrossrefPubMedGoogle Scholar
  • 2 Rabanal R M, Bonkanka C X, Hernández-Pérez M, Sánchez-Mateo C C. Analgesic and topical anti-inflammatory activity of Hypericum canariense L. and Hypericum glandulosum Ait.  J Ethnopharmacol. 2005;  96 591-596
    CrossrefPubMedGoogle Scholar
  • 3 Sánchez-Mateo C C, Bonkanka C X, Hernández-Pérez M, Rabanal R M. Evaluation of the analgesic and topical anti-inflammatory effects of Hypericum reflexum L. fil.  J Ethnopharmacol. 2006;  107 1-6
    CrossrefPubMedGoogle Scholar
  • 4 Mentz L A, Lutzemberger L C, Schenkel E P. Da flora medicinal do Rio Grande do Sul: notas sobre a obra de D'Avila (1910).  Caderno de Farmácia. 1997;  15 25-47
    PubMedGoogle Scholar
  • 5 Viana A F, Heckler A P, Fenner R, Rates S M K. Antinociceptive activity of Hypericum caprifoliatum and Hypericum polyanthemum (Guttiferae).  Braz J Med Biol Res. 2003;  36 631-634
    PubMedGoogle Scholar
  • 6 Ferraz A B F, Bordignon S A L, Staats C, Schripsema J, von Poser G L. Benzopyrans from Hypericum polyanthemum.  Phytochemistry. 2001;  57 1227-1230
    CrossrefPubMedGoogle Scholar
  • 7 Gnerre C, von Poser G L, Ferraz A, Viana A, Testa B, Rates S M K. Monoamine oxidase inhibitory activity of some Hypericum species native to South Brazil.  J Pharm Pharmacol. 2001;  53 1273-1279
    CrossrefPubMedGoogle Scholar
  • 8 Dall'Agnol R, Ferraz A, Bernardi A P, Albring D, Nör C, Schapoval E E S, von Poser G L. Bioassay-guided isolation of antimicrobial benzopyrans and phloroglucinol derivatives from Hypericum species.  Phytother Res. 2005;  19 291-293
    CrossrefPubMedGoogle Scholar
  • 9 Ferraz A B F, Grivicich I, von Poser G L, Faria D H, Kayser G B, Schwartsmann G, Henriques A T, da Rocha A B. Antitumor activity of three benzopyrans isolated from Hypericum polyanthemum.  Fitoterapia. 2005;  76 210-215
    CrossrefPubMedGoogle Scholar
  • 10 Grivicich I, Ferraz A, Faria D H, Regner A, Schwartsmann G, Henriques A T, von Poser G L, da Rocha A B. Synergistic effect of three benzopyrans isolated from Hypericum polyanthemum in U-373 MG glioblastoma cell line.  Phytother Res. 2008;  22 1577-1580
    CrossrefPubMedGoogle Scholar
  • 11 Ferraz A B F, da Silva J, Deimlimg L I, Santos-Mello R, Sharlau A, von Poser G L, Picada J N. Genotoxicity evaluation of three benzopyrans from Hypericum polyanthemum.  Planta Med. 2009;  75 37-40
    Article in Thieme ConnectPubMedGoogle Scholar
  • 12 Cargnin S T, de Matos Nunes J, Haas J S, Baladão L F, Cassel E, Vargas R F, Rech S B, von Poser G L. Supercritical fluid extraction and high performance liquid chromatographic determination of benzopyrans and phloroglucinol derivative in Hypericum polyanthemum.  J Chromatogr B Anal Technol Biomed Life Sci. 2010;  878 83-87
    CrossrefPubMedGoogle Scholar
  • 13 Brasil Congresso Nacional .Lei n. 11794. Regulamenta o inciso VII do § 1° do artigo 225 da Constituição Federal, estabelecendo procedimentos para o uso científico de animais. Revoga a lei nº 6638, de 8 de maio de 1979 e dá outras providências. D.O.U., Brasília, 8 de outubro de 2008. 
    PubMedGoogle Scholar
  • 14 Bankowski Z. CIOMS. Council for International Organization of Medical Sciences International guiding principles for biomedical research involving animals. 1985 http://www.cioms.ch/frame_1985_texts_of_guidelines.htm Accessed September 30, 2009
    PubMedGoogle Scholar
  • 15 Dunham N W, Miya T S. A note on a simple apparatus for detecting neurological deficit in rats and mice.  J Am Pharm Assoc Am Pharm Assoc (Baltim). 1957;  46 208-209
    PubMedGoogle Scholar
  • 16 Le Bars D, Gozariu M, Cadden S W. Animal models of nociception.  Pharmacol Rev. 2001;  53 597-652
    PubMedGoogle Scholar
  • 17 Pearl J, Stander H, McKean D B. Effects of analgesics and other drugs on mice in phenylquinone and rotorod tests.  J Pharmacol Exp Ther. 1969;  167 9-13
    PubMedGoogle Scholar
  • 18 Heckler A P M, Viana A F, Fenner R, Nor C, Kliemann M, do Rego J C, Costentin J, von Poser G L, Rates S M K. Atividade antinociceptiva de uliginosina isolada de Hypericum polyanthemum (Guttiferae). Águas de Lindóia; 20ª Reunião da Federação de Sociedades de Biologia Experimental 2005
    PubMedGoogle Scholar
  • 19 Parsons A A, Bingham S, Raval P, Read S, Thompson M, Upton N. Tonabersat (SB-220453) a novel benzopyran with anticonvulsant properties attenuates trigeminal nerve-induced neurovascular reflexes.  Br J Pharmacol. 2001;  132 1549-1557
    CrossrefPubMedGoogle Scholar
  • 20 Prasanna S, Manivannan E, Chaturvedi S C. Quantitative structure-activity relationship analysis of a series of 2,3-diaryl benzopyran analogues as novel selective cyclooxygenase-2 inhibitors.  Bioorg Med Chem Lett. 2004;  14 4005-4011
    CrossrefPubMedGoogle Scholar
  • 21 Gierse J, Nickols M, Leahy K, Warner J, Zhang Y, Cortes-Burgos L, Carter J, Seibert K, Masferrer J. Evalaution of COX-1/COX-2 selectivity and potency of a new class of COX-2 inhibitors.  Eur J Pharmacol. 2008;  588 93-98
    CrossrefPubMedGoogle Scholar
  • 22 Eissa A A M, Farag N A H, Soliman G A H. Synthesis, biological evaluation and docking studies of novel benzopyranone congeners for their expected activity as anti-inflammatory, analgesic and antipyretic agents.  Bioorg Med Chem. 2009;  17 5059-5070
    CrossrefPubMedGoogle Scholar
  • 23 Cichewicz D L. Synergistic interactions between cannabinoid and opioid analgesics.  Life Sci. 2004;  74 1317-1324
    CrossrefPubMedGoogle Scholar
  • 24 Welch S P. Interaction of the cannabinoid and opioid systems in the modulation of nociception.  Int Rev Psychiatry. 2009;  21 143-151
    CrossrefPubMedGoogle Scholar
  • 25 Mennini T, Gobbi M. The antidepressant mechanism of Hypericum perforatum.  Life Sci. 2004;  75 1021-1027
    CrossrefPubMedGoogle Scholar
  • 26 Chen F, Rezvani A H, Lawrence A J. Autoradiographic quantification of neurochemical markers of serotonin, dopamine and opioid systems in rat brain mesolimbic regions following chronic St. John's wort treatment.  Naunyn Schmiedebergs Arch Pharmacol. 2003;  367 126-133
    CrossrefPubMedGoogle Scholar
  • 27 Perfumi M, Mattioli L, Cucculelli M, Massi M. Reduction of ethanol intake by chronic treatment with Hypericum perforatum, alone or combined with naltrexone in rats.  J Psychopharmacol. 2005;  19 448-454
    CrossrefPubMedGoogle Scholar

1 These authors have contributed equally to the studies presented in this manuscript.

Prof. Dr. Stela Maris Kuze Rates

Programa de Pós-graduação em Ciências Farmacêuticas
Universidade Federal do Rio Grande do Sul

Av. Ipiranga 2752

Porto Alegre, RS 90610–000

Brazil

Phone: + 55 51 33 08 54 55

Fax: + 55 51 33 08 54 37

Email: stela.rates@ufrgs.br