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巴豆(Croton cajucara Benth.)精油对啮齿动物的抗炎和镇痛作用

Anti-inflammatory and antinociceptive effects in rodents of the essential oil of Croton cajucara Benth.

作者信息

Bighetti E J, Hiruma-Lima C A, Gracioso J S, Brito A R

机构信息

Departimento de Farmacologia, Faculadade de Ciências Medicas, Kingston, Brazil.

出版信息

J Pharm Pharmacol. 1999 Dec;51(12):1447-53. doi: 10.1211/0022357991777100.

Abstract

The plant Croton cajucara Benth. (Euphorbiaceae) is widely used in Amazonian folk medicine for the treatment of a wide range of illnesses. In this investigation the analgesic and anti-inflammatory properties of the essential oil from the bark of C. cajucara Benth., administered orally, were determined in several standard rodent models of pain and inflammation. We observed that pretreatment with essential oil significantly reduced the latency of sleeping time evoked by pentobarbital compared with the control group (P < 0.001). Doses of 100 or 1000 mg kg(-1) also increased the sleeping time induced by pentobarbital (30.9 +/- 3.91 and 52.1 +/- 15.6 min, respectively) compared with the negative control (12.4 +/- 4.27 min). We investigated the antinociceptive effect of the essential oil in chemical (acetic acid) and thermal (hot-plate) models of nociception in mice. Dipyrone (200 mg kg(-1)) and the highest doses of the essential oil (1000 mg kg(-1)) significantly inhibited acetic acid-induced abdominal constriction in mice (5.00 +/- 1.38 and 6.8 +/- 2.1 constrictions, respectively) compared with the negative control (33.1 +/- 2). The same dose of essential oil also raised the pain thresholds of mice in the hot-plate test and significantly (P < 0.05) increased the latency at all observation times. In acetic acid-induced abdominal constriction in mice pretreatment of the animals with naloxone (5 mg kg(-1)) significantly reversed the analgesic effect of morphine and of the essential oil at the highest dose (1000 mg kg(-1)). The essential oil of C. cajucara was also investigated for its anti-inflammatory properties. At the lowest dose (100 mg kg(-1)) the essential oil had anti-inflammatory effects in animal models of acute (carrageenin-induced paw oedema in mice) and chronic (cotton pellet granuloma) inflammation. The essential oil at doses of 50, 100 and 200 mg kg(-1) significantly and dose-dependently inhibited carrageenan-induced oedema (49 +/- 5; 37 +/- 5; 34 +/- 8 mg, respectively) compared with the negative control (74 +/- 8 mg). The essential oil (100 mg kg(-1)) also inhibited chronic inflammation by 38% whereas diclofenac inhibited it by 36%. However, the essential oil did not inhibit the migration of neutrophils into the peritoneal cavity. These data show that the essential oil from C. cajucara contains compounds that had a significant antinociceptive effect when the oil was administered at the highest dose. This effect seems to be related to interaction with the opioid system. The essential oil also had a significant anti-inflammatory effect in acute and chronic inflammation models when administered at lower doses. This effect seems to be related to cyclooxygenase inhibition.

摘要

巴豆属植物 Cajucara Benth.(大戟科)在亚马逊民间医学中被广泛用于治疗多种疾病。在本研究中,通过几种标准的啮齿动物疼痛和炎症模型,测定了口服的 Cajucara Benth. 树皮精油的镇痛和抗炎特性。我们观察到,与对照组相比,精油预处理显著缩短了戊巴比妥诱发的睡眠时间潜伏期(P < 0.001)。与阴性对照组(12.4 ± 4.27 分钟)相比,100 或 1000 mg kg⁻¹ 的剂量也增加了戊巴比妥诱导的睡眠时间(分别为 30.9 ± 3.91 和 52.1 ± 15.6 分钟)。我们在小鼠的化学(乙酸)和热(热板)伤害感受模型中研究了精油的抗伤害感受作用。与阴性对照组(33.1 ± 2)相比,双氯芬酸(200 mg kg⁻¹)和最高剂量的精油(1000 mg kg⁻¹)显著抑制了小鼠乙酸诱导的腹部收缩(分别为 5.00 ± 1.38 和 6.8 ± 2.1 次收缩)。相同剂量的精油在热板试验中也提高了小鼠的疼痛阈值,并在所有观察时间显著(P < 0.05)延长了潜伏期。在小鼠乙酸诱导的腹部收缩试验中,用纳洛酮(5 mg kg⁻¹)预处理动物可显著逆转吗啡和最高剂量(1000 mg kg⁻¹)精油的镇痛作用。还研究了 Cajucara Benth. 精油的抗炎特性。在最低剂量(100 mg kg⁻¹)时,该精油在急性(角叉菜胶诱导的小鼠足肿胀)和慢性(棉球肉芽肿)炎症动物模型中具有抗炎作用。与阴性对照组(74 ±  8 mg)相比,50、100 和 200 mg kg⁻¹ 剂量的精油显著且呈剂量依赖性地抑制了角叉菜胶诱导的水肿(分别为 49 ± 5;37 ± 5;34 ± 8 mg)。精油(100 mg kg⁻¹)也使慢性炎症抑制了 38%,而双氯芬酸抑制了 36%。然而,该精油并未抑制中性粒细胞向腹腔的迁移。这些数据表明,Cajucara Benth. 精油含有在最高剂量给药时具有显著抗伤害感受作用的化合物。这种作用似乎与阿片样物质系统的相互作用有关。该精油在较低剂量给药时,在急性和慢性炎症模型中也具有显著的抗炎作用。这种作用似乎与环氧化酶抑制有关。

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