Nascimento Nilberto Robson Falcão, Refosco Rafael Mohana De Carvalho, Vasconcelos Elainne Cristine Félix, Kerntopf Marta Regina, Santos Cláudia Ferreira, Batista Francisco José Arnaud, De Sousa Clauber Mota, Fonteles Manassés Claudino
Institute for Biomedical Science, Veterinary College, State University of Ceará, Fortaleza, Ceará, Brazil.
J Pharm Pharmacol. 2009 Mar;61(3):361-6. doi: 10.1211/jpp/61.03.0011.
1,8-Cineole is a monoterpene with anti-inflammatory, vascular and intestinal smooth muscle relaxant activity. We have evaluated the potential bronchodilatatory activity of this compound.
1,8-Cineole was tested against carbachol, histamine, K+ 80 mM and ovalbumin-induced bronchial contractions in Wistar rat or guinea-pig tissues. Some of the guinea-pigs had been previously sensitized with an intramuscular injection of 5% (w/v) ovalbumin/saline solution. Control animals received 0.3 ml saline. In separate experimental groups the response to 1,8-cineole (1-30 mg/kg), phenoterol (0.05-5 mg/kg) or vehicle (0.3% Tween in saline) was studied.
1,8-Cineole decreased, in vivo, rat bronchial resistance with similar efficacy as phenoterol (66.7 +/- 3.2% vs 72.1 +/- 5.3%). On the other hand, the maximal relaxant response to 1,8-cineole in carbachol-precontracted rat tracheas was 85.5 +/- 5.7% (IC50 = 408.9 (328-5196) microg/ml) compared with 80.2 +/- 4.8% (IC50 = 5.1 (4.3-6.1) microg/ml) with phenoterol. The addition of 1,8-cineole to guinea-pig tracheal rings tonically contracted with K+ 80 mM induced a concentration-related relaxation. The maximal relaxation elicited by 1,8-cineole was 113.6 +/- 11.7% (IC50 127.0 (115.9-139.2) microg/ml) compared with 129.7 +/- 14.6% (IC50 0.13 (0.12-0.14) microg/ml) achieved after phenoterol administration. In addition, the incubation of tracheal rings with 1,8-cineole (100, 300 or 1000 microg/ml), 15 min before inducing phasic contractions with K+ 80 mM, decreased the maximal amplitude of the contraction by 31.6 +/- 4.6, 75.7 +/- 2.7 and 92.2 +/- 1.5%, respectively. In another set of experiments, neither the maximal response nor the IC50 for the 1,8-cineole-induced relaxation were different between normal and ovalbumin-sensitized tissues. Moreover, the relaxation of bronchial rings contracted after exposure to 1 microg/ml ovalbumin occurred at a faster rate in rings pre-incubated with 1,8-cineole when compared with rings pre-incubated with vehicle only (Tween 0.3%). Therefore, in the first minute after the antigen challenge, the tracheal tissue relaxed after the peak contraction by 6.5, 21.4 (P < 0.05 vs control) and 66.9% (P < 0.05 vs control) in the presence of 100, 300 or 1000 microg/ml 1,8-cineole, respectively.
1,8-Cineole relaxed rat and guinea-pig (nonsensitized and ovalbumin-sensitized) airway smooth muscle by a nonspecific mechanism.
1,8-桉叶素是一种具有抗炎、血管及肠道平滑肌舒张活性的单萜类化合物。我们评估了该化合物潜在的支气管舒张活性。
在Wistar大鼠或豚鼠组织中，检测1,8-桉叶素对卡巴胆碱、组胺、80 mM K⁺及卵清蛋白诱导的支气管收缩的作用。部分豚鼠先前已通过肌肉注射5%（w/v）卵清蛋白/生理盐水溶液进行致敏。对照动物给予0.3 ml生理盐水。在不同实验组中，研究了对1,8-桉叶素（1 - 30 mg/kg）、非诺特罗（0.05 - 5 mg/kg）或溶媒（0.3%吐温生理盐水）的反应。
在体内，1,8-桉叶素降低大鼠支气管阻力的效果与非诺特罗相似（66.7±3.2%对72.1±5.3%）。另一方面，在卡巴胆碱预收缩的大鼠气管中，1,8-桉叶素的最大舒张反应为85.5±5.7%（IC50 = 408.9（328 - 5196）μg/ml），而非诺特罗为80.2±4.8%（IC50 = 5.1（4.3 - 6.1）μg/ml）。向用80 mM K⁺使张力性收缩的豚鼠气管环中加入1,8-桉叶素可诱导浓度相关的舒张。1,8-桉叶素引起的最大舒张为113.6±11.7%（IC50 127.（115.9 - 139.）μg/ml），而非诺特罗给药后为129.7±14.6%（IC50 0.13（0.12 - 0.14）μg/ml）。此外，在用80 mM K⁺诱导相性收缩前15分钟，将气管环与1,8-桉叶素（100、300或1000 μg/ml）孵育，可使收缩的最大幅度分别降低31.6±4.6%、75.7±2.7%和92.2±1.5%。在另一组实验中，正常组织和卵清蛋白致敏组织中，1,8-桉叶素诱导舒张的最大反应和IC50均无差异。此外，与仅用溶媒（0.3%吐温）预孵育的气管环相比，用1,8-桉叶素预孵育的气管环在暴露于1 μg/ml卵清蛋白后收缩的支气管环舒张速度更快。因此，在抗原激发后的第一分钟，在存在100、300或1000 μg/ml 1,8-桉叶素的情况下，气管组织在收缩峰值后分别舒张6.5%、21.4%（与对照组相比P < 0.05）和66.9%（与对照组相比P < 0.05）。
1,8-桉叶素通过非特异性机制使大鼠和豚鼠（未致敏和卵清蛋白致敏）气道平滑肌舒张。
