Antinociceptive Properties of 1,8-Cineole and β-Pinene, from the Essential Oil of Eucalyptus camaldulensis Leaves, in Rodents

Abstract

1,8-Cineole (cineole) and β-pinene, two monoterpenes isolated from the essential oil obtained from Eucalyptus camaldulensis Dehn leaves were tested for antinociceptive properties. Tail-flick and hot-plate methods, reflecting the spinal and supraspinal levels, respectively, were used in mice and/or rats using morphine and naloxone for comparison. Cineole exhibited an antinociceptive activity comparable to that of morphine, in both algesic stimuli. A significant synergism between cineole and morphine was observed, but naloxone failed to antagonize the effect of cineole. β-Pinene exerted supraspinal antinociceptive actions in rats only and it reversed the antinociceptive effect of morphine in a degree equivalent to naloxone, probably acting as a partial agonist through the μ opioid receptors. From structure-activity relationships of the pairs morphine + cineole and naloxone + β-pinene, it was shown that similarities exist in the stereochemistry and in the respective atomic charges of these molecules. Further studies are in progress in order to elucidate the mechanism of action of the two terpenoids.

Key words

1,8-Cineole - β-pinene - Eucalyptus camaldulensis - Myrtacae - antinociception - in vivo assays - rats - mice

References

• 1 De Sousa D P, Raphael E, Brocksom U, Brocksom T J. Antinociceptive profile of 2-phenylselenenyl-1,8-cineole in mice.  Biol Pharm Bull. 2000;  427 910-1.
• 2 Maia J L, Lima RCP J r, David J P, David J M, Santos F A, Rao V S. Oleanolic acid, a pentacyclic triterpene attenuates the mustard oil-induced colonic nociception in mice.  Biol Pharm Bull. 2006;  29 82-5.
• 3 Giamakis A, Kretsi O, Chinou I B, Ganis-Spyropoulos C. Eucalyptus camaldulensis: Volatiles from immature flowers and high production of 1,8-cineole and β-pinene by in vitro cultures.  Phytochemistry. 2001;  58 351-5.
• 4 Tsiri D O, Kretsi O, Chinou I B, Spyropoulos C K. Composition of fruit volatiles and annual changes in the volatiles of leaves of Eucalyptuscamaldulensis Dehn. growing in Greece.  Flav Fragr J. 2003;  18 244-7.
• 5 Ghisalberti E L. Bioactive acylpholoroglucinol derivatives from Eucalyptus species.  Phytochemistry. 1996;  41 7-22.
• 6 Levison K K, Takayama K, Okabe K, Nagai T. Formulation optimization of indomethacine gels containing a combination of three kinds of cyclic monoterpenes as percutaneous penetration enhancers.  J Pharm Pharmacol. 1994;  83 1367-72.
• 7 Juergens U R, Stober M, Schmidt-Schilling L, Kleuver T, Vetter H. Anti-inflammatory effects of eucalyptol (1,8-cineole) in bronchial asthma: inhibition of arachidonic acid metabolism in human blood monocytes ex vivo.  Eur J Med Res. 1998;  17 407-12.
• 8 Juergens U R, Stober M, Vetter H. Inhibition of cytokine production and arachidonic acid metabolism by eucalyptol (1,8-cineole) in human blood monocytes in vitro .  Eur J Med Res. 1998;  17 508-10.
• 9 Lahlou S, Figueierdo A F, Magalhaes P J, Leal-Cardoso J H. Cardiovascular effects of 1,8-cineole, a terpenoid oxide present in many plant essential oils, in normotensive rats.  Can J Physiol Pharmacol. 2002;  80 1125-31.
• 10 Sadraei H, Asghari G R, Hajhashemi V, Kolagar A, Ebrahimi M. Spasmolytic activity of essential oil and various extracts of Ferula gummosa Boiss, on ileum contractions.  Phytomedicine. 2001;  8 370-6.
• 11 Filipowicz N, Kaminski M, Kurlenda J, Asztemborska M, Ochocka J R. Antibacterial and antifungal activity of juniper berry oil and its selected components.  Phytother Res. 2003;  17 227-31.
• 12 Ndiege I O, Budenberg W J, Otieneo D O, Hassanali A. 1,8-Cineol: an attractant for the banana weevil, Cosmopolites sordidus .  Phytochemistry. 1996;  42 369-71.
• 13 Adams R P. Identification of essential oil components by gas chromatography/quadropole mass spectroscopy. Carol Stream: Allured Publishing 2001.
• 14 Massada Y. Analysis of essential oil by gas chromatography and spectrometry. New York; John Wiley & Sons 1976
• 15 Eddy N B, Leimbach D J. Synthetic analgesics. II Diethienylbutanyl and dithienylbutamines.  J Pharmacol Exp Ther. 1953;  107 385-93.
• 16 D’Amour F E, Smith D L. A method for determining loss of pain sensation.  J Pharmacol Exp Ther. 1941;  72 74-9.
• 17 Vaz Z R, Filho V C, Yunes R A, Calixto J B. Antinociceptive action of 2-(4-bromophenzoy)-3-methyl-4,6-dimethoxy benzofuran, a novel xanthoxylin derivative, on chemical and thermal models of nociception in mice.  J Pharmacol Exp Ther. 1996;  278 304-12.
• 18 Allen F H, Kennard O. 3D search and research using the Cambridge Structural Database.  Chem Design Automation News. 1993;  8 31-7.
• 19 Beckett A H, Casy A F. Synthetic analgesics: stereochemical considerations.  J Pharm Pharmacol. 1954;  6 86-1001.
• 20 Dewey W L, Snyder J W, Harris L S, Howes J F. The effects of narcotics and narcotic antagonists on the tail flick response in spinal mice.  J Pharm Pharmacol. 1969;  21 548-50.
• 21 Schmauss C, Yaksh T L. In vivo studies on spinal opiate receptorsystems mediating antinociception. II Pharmacological profiles suggesting a differential association of mu, delta and kappa receptors with visceral chemical and cutaneous thermal stimuli in the rat.  J Pharmacol Exp Ther. 1984;  228 -12.
• 22 Danneman P J. Monitoring of analgesia.  Anesth Analg. 1997;  6 3-103.
• 23 Santos F A, Rao V S. Antiinflammatory and antinociceptive effects of 1,8-cineole a terpenoid oxide present in many plant essential oils.  Phytother Res. 2000;  14 249-54.
• 24 llich P A, King T A, Grau J W. Impact of shock on pain reactivity: I. Whether hypo- or hyper- algesia is observed depends on how pain reactivity is tested.  J Exp Psychol Anim Behav Process. 1995;  21 331-47.
• 25 King T E, Joynes R L, Grau J W. Tail-flick test: II. The role of supraspinal system and avoidance learning.  Behav Neurosci. 1997;  111 754-67.
• 26 Gelot A, Frances B, Roussin A, Latapie J -P, Zajac J -M. Anti-opioid efficacy of neuropeptide FF in morphine-tolerant mice.  Brain Res. 1998;  808 66-73.