Planta Med 2006; 72(1): 34-39
DOI: 10.1055/s-2005-873150
Original Paper
Pharmacology
© Georg Thieme Verlag KG Stuttgart · New York

Attenuation of Visceral Nociception by α- and β-Amyrin, a Triterpenoid Mixture Isolated from the Resin of Protium heptaphyllum, in Mice

Roberto C. P. Lima-Júnior1 , Francisco A. Oliveira1 , Luilma A. Gurgel1 , Ítalo J. M. Cavalcante1 , Kelcyana A. Santos1 , Deive A. Campos1 , Cinthia A. L. Vale1 , Regilane M. Silva1 , Mariana H. Chaves2 , Vietla S. N. Rao1 , Flávia A. Santos1
  • 1Department of Physiology and Pharmacology, Federal University of Ceara, Fortaleza, CE, Brazil
  • 2Department of Organic Chemistry, Federal University of Piaui, Teresina, PI, Brazil
Weitere Informationen

Publikationsverlauf

Received: February 15, 2005

Accepted: June 20, 2005

Publikationsdatum:
10. November 2005 (online)

Abstract

In the search for novel natural compounds effective against visceral nociception, the triterpenoid mixture α- and β-amyrin, isolated from Protium heptaphyllum resin, was assessed in two established mouse models of visceral nociception. Mice were pretreated orally with α- and β-amyrin (3, 10, 30, and 100 mg/kg) or vehicle, and the pain-related behavioral responses to intraperitoneal cyclophosphamide or to intracolonic mustard oil were analyzed. The triterpenoid mixture showed a dose-related significant antinociception against the cyclophosphamide-induced bladder pain, and at 100 mg/kg, the nociceptive behavioral expression was almost completely suppressed. Intracolonic mustard oil-induced nociceptive behaviors were maximally inhibited by 10 mg/kg α- and β-amyrin mixture in a naloxone-reversible manner. While pretreatment with ruthenium red (3 mg/kg, s. c.), a non-specific transient receptor potential cation channel V1 (TRPV1) antagonist, also caused significant inhibition, the α2-adrenoceptor antagonist, yohimbine (2 mg/kg, s. c.), showed no significant effect. The triterpene mixture (10 mg/kg, p. o.) neither altered significantly the pentobarbital sleeping time, nor impaired the ambulation or motor coordination in open-field and rotarod tests, respectively, indicating the absence of sedative or motor abnormalities that could account for its antinociception. These results indicate that the antinociceptive potential of α- and β-amyrin possibly involves the opioid and vanilloid (TRPV1) receptor mechanisms and further suggests that it could be useful to treat visceral pain of intestinal and pelvic origins.

References

  • 1 Saini A C, Ramos M FS, de Lima M O, Santos R, Ferreira F E, Soares E C. et al . Evaluation of anti-inflammatory-related activity of essential oils from the leaves and resin of species of Protium .  J Ethnopharmacol. 1999;  66 57-69
  • 2 Bandeira P N, Pessoa O DL, Trevisan M TS, Lemos T LG. Metabólitos secundários de Protium heptaphyllum March.  Quim Nova. 2002;  25 1078-80
  • 3 Oliveira F A, Vieira-Júnior G M, Chaves M H, Almeida F RC, Santos K A, Martins F S. et al . Gastroprotective effect of the mixture of α- and β-amyrin from Protium heptaphyllum: Role of capsaicin-sensitive afferent neurons.  Planta Med. 2004;  70 780-2
  • 4 Oliveira F A, Lima-Júnior R CP, Cordeiro W M, Vieira-Júnior G M, Chaves M H, Almeida F RC. et al . Pentacyclic triterpenoid, alpha-, beta-amyrins, suppress the scratching behavior in a mouse model of pruritus.  Pharmacol Biochem Behav. 2004;  78 719-25
  • 5 Davis J B, Gray J, Gunthorpe M J, Hatcher J P, Davey P T, Harries M H. et al . Vanilloid receptor-1 is essential for inflammatory thermal hyperalgesia.  Nature. 2000;  405 183-7
  • 6 Caterina M J, Leffler A, Malmberg A B, Martin W J, Trafton J, Petersen-Zeitz K R. et al . Impaired nociception and pain sensation in mice lacking the vanilloid receptor.  Science. 2000;  288 306-13
  • 7 Mansour A, Fox C A, Akil H, Watson S J. Opioid receptor mRNA expression in the rat CNS: anatomical and functional implications.  Trends Neurosci. 1995;  18 22-9
  • 8 Ji R R, Zhang Q, Law P , Low H H, Elde R, Hokfelt T. Expression of μ-,δ-, and κ-opioid receptor-like immunoreactivities in rat dorsal root ganglia after carrageenan-induced inflammation.  J Neurosci. 1995;  15 8156-66
  • 9 Sterner O, Szallasi A. Novel natural vanilloid receptor agonists: new therapeutic targets for drug development.  Trends Pharmacol Sci. 1999;  20 459-65
  • 10 Otuki M F, Ferreira J, Vieira-Lima F, Meyre-Silva C, Malheiros A, Mull L A. et al . Antinociceptive properties of mixture of {alpha}-amyrin and {beta}-amyrin triterpenes: evidence for participation of PKC and PKA pathways.  J Pharmacol Exp Ther. 2005;  313 310-8
  • 11 Gallegos R S, Roque N F. Análise de Misturas de Triterpenos por 13C NMR.  Quim Nova. 1990;  13 278-81
  • 12 Mahato S B, Sen S. Advances in triterpenoid research, 1990 - 1994.  Phytochemistry. 1997;  44 1185-236
  • 13 Palma P C, Villaca Junior C J, Netto Junior N R. N-Acetylcysteine in the prevention of cyclophosphamide induced haemorrhagic cystitis.  Int Surg. 1986;  71 36-7
  • 14 Olivar T, Laird J MA. Cyclophosphamide cystitis in mice: behavioural characterization and correlation with bladder inflammation.  Eur J Pain. 1999;  3 141-9
  • 15 Laird J MA, Maritnez-Caro L, Garcia-Nicas E, Cervero F. A new model of visceral pain and referred hyperalgesia in the mouse.  Pain. 2001;  92 335-42
  • 16 Darias V, Abdala S, Martin-Herrera D, Tello M L, Vega S. CNS effects of a series of 1,2,4-triazolyl heterocarboxylic derivatives.  Pharmazie. 1998;  53 477-81
  • 17 Archer J. Tests for emotionality in rats and mice. A review.  Anim Behav. 1973;  21 205-35
  • 18 Rosland J H, Hunskaar S, Hole K. Diazepam attenuates morphine antinociception test-dependently in mice.  Pharmacol Toxicol. 1990;  66 382-6
  • 19 Cervero F. Sensory innervation of the viscera: peripheral basis of visceral pain.  Physiol Rev. 1994;  74 95-138
  • 20 Koster R, Anderson M, de Beer E J. Acetic acid for analgesic screening.  Fed Proc. 1959;  18 412
  • 21 Kim K A, Lee J S, Park H J, Kim J W, Kim C J, Shim I S. et al . Inhibition of cytochrome P450 activities by oleonolic acid and ursolic acid in human liver microsomes.  Life Sci. 2004;  74 2769-79
  • 22 Maggi C A, Lecci A, Santicioli P, Del Bianco E, Giuliani S. Cyclophosphamide cystitis in rats: involvement of capsaicin-sensitive primary afferents.  Auton Nerv Syst. 1992;  38 201-8
  • 23 Kobayashi Y. The nociceptive and anti-nociceptive effects of evodiamine from fruits of Evodia rutaecarpa in mice.  Planta Med. 2003;  69 425-8
  • 24 Jordt S E, Bautista D, Chuang H -H, Mckemy D D, Zygmunt P M, Hogestatt E D. et al . Mustard oils and cannabinoids excite sensory nerve fibers through the TRP channel ANKTMI.  Nature. 2004;  427 260-5
  • 25 Gebhart G F. Visceral nociception: consequences, modulation and the future.  Eur J Anaesthesiol. 1995;  10 24-7
  • 26 Wood J N. Recent advances in understanding molecular mechanisms of primary afferent activation.  Gut. 2004;  53 119
  • 27 Miampamba M, Chery-Croze S, Detolle-Sarbach S, Guez D, Chayvialle J A. Antinociceptive effects of oral clonidine and S12813 - 4 in acute colon inflammation in rats.  Eur J Pharmacol. 1996;  308 251-9
  • 28 Black D, Trevethick M. The kappa opioid receptor is associated with the perception of visceral pain.  Gut. 1998;  43 312-3

F. A. Santos

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