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双丁香烯在混合粒细胞性哮喘哮喘小鼠模型中表现出抗炎和抗哮喘作用。

Biseugenol Exhibited Anti-Inflammatory and Anti-Asthmatic Effects in an Asthma Mouse Model of Mixed-Granulocytic Asthma.

机构信息

Departament of Chemistry, Universidade Federal de São Paulo, São Paulo 09972-270, Brazil.

Departament of Biological Sciences, Universidade Federal de São Paulo, São Paulo 09972-270, Brazil.

出版信息

Molecules. 2020 Nov 18;25(22):5384. doi: 10.3390/molecules25225384.

Abstract

In the present work, the anti-inflammatory and antiasthmatic potential of biseugenol, isolated as the main component from -hexane extract from leaves of and chemically prepared using oxidative coupling from eugenol, was evaluated in an experimental model of mixed-granulocytic asthma. Initially, in silico studies of biseugenol showed good predictions for drug-likeness, with adherence to Lipinski's rules of five (RO5), good Absorption, Distribution, Metabolism and Excretion (ADME) properties and no alerts for Pan-Assay Interference Compounds (PAINS), indicating adequate adherence to perform in vivo assays. Biseugenol (20 mg·kg) was thus administered intraperitoneally (four days of treatment) and resulted in a significant reduction in both eosinophils and neutrophils of bronchoalveolar lavage fluid in ovalbumin-sensitized mice with no statistical difference from dexamethasone (5 mg·kg). As for lung function parameters, biseugenol (20 mg·kg) significantly reduced airway and tissue damping in comparison to ovalbumin group, with similar efficacy to positive control dexamethasone. Airway hyperresponsiveness to intravenous methacholine was reduced with biseugenol but was inferior to dexamethasone in higher doses. In conclusion, biseugenol displayed antiasthmatic effects, as observed through the reduction of inflammation and airway hyperresponsiveness, with similar effects to dexamethasone, on mixed-granulocytic ovalbumin-sensitized mice.

摘要

在本工作中,我们评估了双丁香烯作为 - 己烷提取物中主要成分从丁香酚化学制备而来的抗炎和抗哮喘潜能,该提取物分离自 ,并用丁香酚氧化偶联法化学制备而来,在混合粒细胞性哮喘的实验模型中进行了评估。最初,双丁香烯的计算研究表明其具有良好的药物相似性预测,符合 Lipinski 的五规则(RO5),具有良好的吸收、分布、代谢和排泄(ADME)特性,且没有 Pan-Assay Interference Compounds(PAINS)警报,表明其具有足够的适应性来进行体内检测。因此,双丁香烯(20 mg·kg)通过腹腔内给药(治疗四天),导致卵清蛋白致敏小鼠支气管肺泡灌洗液中的嗜酸性粒细胞和中性粒细胞显著减少,与地塞米松(5 mg·kg)相比无统计学差异。就肺功能参数而言,与卵清蛋白组相比,双丁香烯(20 mg·kg)显著降低气道和组织阻尼,与阳性对照地塞米松具有相似的疗效。与地塞米松相比,双丁香烯降低了对静脉内乙酰甲胆碱的气道高反应性,但在较高剂量时不如地塞米松。总之,双丁香烯在混合粒细胞性卵清蛋白致敏小鼠中显示出抗哮喘作用,通过减少炎症和气道高反应性来观察,其作用与地塞米松相似。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3aed/7698799/301d42d30508/molecules-25-05384-g001.jpg

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