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单萜α-水芹烯在啮齿动物中的抗伤害活性:可能的作用机制。

Antinociceptive activity of the monoterpene α-phellandrene in rodents: possible mechanisms of action.

机构信息

Medicinal Plants Research Center, Federal University of Piauí, Parnaíba, Piauí Department of Chemistry, Federal University of Sergipe, Aracajú, Sergipe, Brazil.

出版信息

J Pharm Pharmacol. 2012 Feb;64(2):283-92. doi: 10.1111/j.2042-7158.2011.01401.x. Epub 2011 Dec 8.

Abstract

OBJECTIVES

The aim of this work was to investigate the antinociceptive property of α-phellandrene (α-PHE) in experimental nociception models and possible mechanisms involved.

METHODS

Mass spectrometry was used to evaluate the purity and molecular mass of α-PHE. Macrophages from mice peritoneal cavity were used in an MTT test. Rodents were used in tests of chemical and mechanical nociception. In the study of the mechanisms, the animals were treated with pharmacological tools and then submitted to the glutamate test.

KEY FINDINGS

α-PHE purity was 98.2% and molecular mass 136.1 Da. α-PHE did not show cytotoxicity. In the writhing and capsaicin tests, α-PHE promoted the antinociceptive effect in all evaluated doses (minimum dose 3.125 mg/kg). In the formalin test, α-PHE (50 mg/kg) was effective in inhibiting both phases. In the glutamate test, the monoterpene (12.5 mg/kg) decreased the nociceptive response. In carrageenan-induced hyperalgesia, α-PHE (50 mg/kg) decreased the hypernociception index. In the study of the mechanisms involved, pretreatment with naloxone reversed the α-PHE antinociceptive effect, the same occurred with glibenclamide, l-arginine, atropine and yohimbine. α-PHE did not show muscle relaxant activity or central depressant effects in open field and rota rod tests.

CONCLUSIONS

α-PHE has an antinociceptive effect and it possibly involves the glutamatergic, opioid, nitrergic, cholinergic and adrenergic systems.

摘要

目的

本研究旨在探讨α-蒎烯(α-PHE)在实验性疼痛模型中的镇痛作用及其可能涉及的机制。

方法

采用质谱法评估α-PHE 的纯度和分子量。使用来自小鼠腹腔的巨噬细胞进行 MTT 试验。使用化学和机械性疼痛模型检测啮齿动物。在机制研究中,动物接受药理学工具处理后,再进行谷氨酸试验。

主要发现

α-PHE 的纯度为 98.2%,分子量为 136.1 Da。α-PHE 无细胞毒性。在扭体和辣椒素试验中,α-PHE 在所有评估剂量下均表现出镇痛作用(最低剂量 3.125 mg/kg)。在福尔马林试验中,α-PHE(50 mg/kg)对两个阶段均有效。在谷氨酸试验中,单萜(12.5 mg/kg)降低了疼痛反应。在角叉菜胶诱导的痛觉过敏中,α-PHE(50 mg/kg)降低了痛觉过敏指数。在涉及的机制研究中,纳洛酮预处理逆转了 α-PHE 的镇痛作用,同样的情况也发生在格列本脲、l-精氨酸、阿托品和育亨宾中。α-PHE 在旷场和转棒试验中没有表现出肌肉松弛活性或中枢抑制作用。

结论

α-PHE 具有镇痛作用,可能涉及谷氨酸能、阿片能、一氧化氮能、胆碱能和肾上腺素能系统。

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