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白杨素(一种从伏毛委陵菜中分离出的黄酮)对炎症反应的抑制作用。关于其作用机制的计算机模拟预测研究。

Suppression of inflammatory response by chrysin, a flavone isolated from Potentilla evestita Th. Wolf. In silico predictive study on its mechanistic effect.

作者信息

Rauf Abdur, Khan Rehan, Raza Muslim, Khan Haroon, Pervez Samreen, De Feo Vincenzo, Maione Francesco, Mascolo Nicola

机构信息

Institute of Chemical Sciences, University of Peshawar, Peshawar, Pakistan; Department of Geology, University of Peshawar, Peshawar, Pakistan.

HEJ Research Institute, Institute of Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan.

出版信息

Fitoterapia. 2015 Jun;103:129-35. doi: 10.1016/j.fitote.2015.03.019. Epub 2015 Mar 24.

Abstract

Flavonoids are the most abundant natural polyphenols widely distributed in plants. Among them, chrysin has recently attracted the attention for its anti-tumor and anti-oxidant activities and also for its protective effects on allergic inflammation. Therefore, in this study, we set out to investigate and characterize the effects of chrysin in classical models of inflammation reasoning that this would expand our knowledge on the pharmacological properties of this flavone. To this aim we have firstly isolated chrysin from Potentilla evestita Th. Wolf. and successively evaluated its anti-inflammatory and analgesic potential on writhing and formalin test and also on carrageenan-induced paw oedema. Finally, the present study was planned to investigate, by the aim of docking analysis, the molecular interaction of this compound on the binding site of COX-1 and COX-2 enzymes. On writhing test, we observed a significant inhibition of writhings after the administration of chrysin at 5.0 and 10.0 mg/kg i.p. (25.00±9.22% and 55.67±7.62% respectively). On formalin test, the flavone at dose of 10.0 mg/kg i.p. displayed its maximum analgesic and anti-inflammatory effect on both early (35.67±7.88%) and late phase (50.57±5.36%) and similarly displayed at 4h a significant anti-inflammatory effect in carrageenan-induced paw oedema. Moreover, in silico analysis of receptor ligand complex shows that chrysin interacts weakly with COX-1 binding site whereas displayed a remarkable interaction with COX-2. These findings suggest that the flavone chrysin isolated from P. evestita Th. Wolf. possesses in vivo anti-inflammatory and anti-nociceptive potential, which are supported in silico by an interaction with COX-2 binding site.

摘要

黄酮类化合物是植物中分布最广泛的天然多酚。其中,白杨素最近因其抗肿瘤和抗氧化活性以及对过敏性炎症的保护作用而受到关注。因此,在本研究中,我们着手研究并表征白杨素在经典炎症模型中的作用,认为这将扩展我们对这种黄酮药理特性的认识。为此,我们首先从伏毛委陵菜中分离出白杨素,然后依次评估其对扭体试验和福尔马林试验以及对角叉菜胶诱导的爪肿胀的抗炎和镇痛潜力。最后,本研究计划通过对接分析来研究该化合物与COX-1和COX-2酶结合位点的分子相互作用。在扭体试验中,我们观察到腹腔注射5.0和10.0mg/kg白杨素后扭体次数显著减少(分别为25.00±9.22%和55.67±7.62%)。在福尔马林试验中,腹腔注射10.0mg/kg剂量的黄酮对早期(35.67±7.88%)和晚期(50.57±5.36%)均显示出最大的镇痛和抗炎作用,并且在角叉菜胶诱导的爪肿胀中,在4小时时同样显示出显著的抗炎作用。此外,受体配体复合物的计算机模拟分析表明,白杨素与COX-1结合位点的相互作用较弱,而与COX-2显示出显著的相互作用。这些发现表明,从伏毛委陵菜中分离出的黄酮类化合物白杨素具有体内抗炎和抗伤害感受的潜力,这在计算机模拟中得到了与COX-2结合位点相互作用的支持。

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