Maia Juliana Lemos, Lima-Júnior Roberto César Pereira, David Juceni Pereira, David Jorge Mauricio, Santos Flávia Almeida, Rao Vietla Satyanarayana
Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceara, Brazil.
Biol Pharm Bull. 2006 Jan;29(1):82-5. doi: 10.1248/bpb.29.82.
Many natural terpenoid compounds from plants exhibit antinociceptive property but very few studies have addressed their efficacy in visceral models of nociception. The present study evaluated the antinociceptive potential of oleanolic acid, a pentacyclic triterpene in the mouse model of colonic nociception induced by mustard oil. We further examined the possible participation of opioid, alpha2-adrenergic, and transient receptor potential vanilloid 1 (TRPV1)-receptors in its mechanism. Mice were pretreated orally with oleanolic acid (3, 10, 30 mg/kg) or vehicle, and the pain-related behavioral responses to intracolonic injection of mustard oil was analysed. Oleanolic acid significantly suppressed the mustard oil-induced nociceptive behaviors at test doses of 10 and 30 mg/kg, in a dose-related manner. The antinociceptive effect of oleanolic acid (30 mg/kg) was significantly blocked by pretreatment with the opioid antagonist, naloxone (2 mg/kg, i.p.), while the alpha2-adrenoceptor antagonist, yohimbine (2 mg/kg, s.c.), had no effect. Pretreatment with ruthenium red (3 mg/kg, s.c.), a non-competitive TRPV1 antagonist alone caused significant inhibition of mustard oil-induced nociception but its co-administration with oleanolic acid produced neither antagonism nor potentiation of oleanolic acid antinociception. In the open-field test that detects sedative or motor abnormality, mice received 30 mg/kg oleanolic acid did not show any per se influence, but significantly inhibited the mustard oil-induced decrease in ambulation frequency. These data demonstrate the visceral antinociceptive potential of oleanolic acid that involves an opioid mechanism and possibly a modulatory influence on vanilloid-receptors, which needs further study.
许多来自植物的天然萜类化合物具有抗伤害感受特性,但很少有研究探讨它们在内脏伤害感受模型中的功效。本研究评估了齐墩果酸(一种五环三萜)在芥子油诱导的结肠伤害感受小鼠模型中的抗伤害感受潜力。我们进一步研究了阿片类、α2-肾上腺素能和瞬时受体电位香草酸亚型1(TRPV1)受体在其作用机制中可能的参与情况。小鼠口服给予齐墩果酸(3、10、30mg/kg)或赋形剂,然后分析结肠内注射芥子油后与疼痛相关的行为反应。齐墩果酸在10和30mg/kg的测试剂量下以剂量相关的方式显著抑制了芥子油诱导的伤害感受行为。阿片类拮抗剂纳洛酮(2mg/kg,腹腔注射)预处理可显著阻断齐墩果酸(30mg/kg)的抗伤害感受作用,而α2-肾上腺素能受体拮抗剂育亨宾(2mg/kg,皮下注射)则无作用。非竞争性TRPV1拮抗剂钌红(3mg/kg,皮下注射)单独预处理可显著抑制芥子油诱导的伤害感受,但与齐墩果酸联合给药既不产生拮抗作用也不增强齐墩果酸的抗伤害感受作用。在检测镇静或运动异常的旷场试验中,接受30mg/kg齐墩果酸的小鼠本身未表现出任何影响,但显著抑制了芥子油诱导的行走频率降低。这些数据证明了齐墩果酸的内脏抗伤害感受潜力,其涉及阿片类机制,可能还对香草酸受体有调节作用,这需要进一步研究。