Oswaldo Cruz Foundation, Brazil.
J Pharm Pharmacol. 2010 Feb;62(2):205-13. doi: 10.1211/jpp.62.02.0008.
In the present study we investigated the antinociceptive, anti-inflammatory and antipyretic effects of 7-hydroxycoumarin (7-HC) in animal models.
The effects of oral 7-HC were tested against acetic acid-induced writhing, formalin test, tail flick test, complete Freund's adjuvant (CFA)-induced hypernociception, carrageenan-induced paw oedema, lipopolysaccharide-induced fever and the rota rod test.
7-HC (3-60 mg/kg) produced a dose-related antinociception against acetic acid-induced writhing in mice and in the formalin test. In contrast, treatment with 7-HC did not prevent thermal nociception in the tail flick test. A single treatment with 7-HC, 60 mg/kg, produced a long-lasting antinociceptive effect against CFA-induced hypernociception, a chronic inflammatory pain stimulus. Notably, at 60 mg/kg per day over 4 days the administration of 7-HC produced a continuous antinociceptive effect against CFA-induced hypernociception. 7-HC (30-120 mg/kg) produced anti-inflammatory and antipyretic effects against carrageenan-induced inflammation and lipopolysaccharide-induced fever, respectively. Moreover, 7-HC was found to be safe with respect to ulcer induction. In the rota rod test, 7-HC-treated mice did not show any motor performance alterations.
The prolonged antinociceptive and anti-inflammatory effects of 7-HC, in association with its low ulcerogenic activity, indicate that this molecule might be a good candidate for development of new drugs for the control of chronic inflammatory pain and fever.
在本研究中,我们研究了 7-羟基香豆素(7-HC)在动物模型中的镇痛、抗炎和退热作用。
测试了口服 7-HC 对乙酸诱导的扭体、福尔马林试验、甩尾试验、完全弗氏佐剂(CFA)诱导的痛觉过敏、角叉菜胶诱导的足肿胀、脂多糖诱导的发热和旋转棒试验的影响。
7-HC(3-60mg/kg)对小鼠的乙酸诱导扭体和福尔马林试验表现出剂量相关的镇痛作用。相比之下,7-HC 治疗不能预防甩尾试验中的热痛觉过敏。单次给予 7-HC(60mg/kg)可产生对 CFA 诱导的痛觉过敏的持久镇痛作用,这是一种慢性炎症性疼痛刺激。值得注意的是,7-HC 以 60mg/kg/天的剂量连续给药 4 天可对 CFA 诱导的痛觉过敏产生持续的镇痛作用。7-HC(30-120mg/kg)对角叉菜胶诱导的炎症和脂多糖诱导的发热分别产生抗炎和退热作用。此外,7-HC 对诱导溃疡具有低的安全性。在旋转棒试验中,7-HC 处理的小鼠未表现出任何运动性能改变。
7-HC 的长时间镇痛和抗炎作用,以及其低溃疡形成活性,表明该分子可能是开发用于控制慢性炎症性疼痛和发热的新药的良好候选物。