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评价倍半萜烯(-)-α- 姜黄醇作为一种新型外周神经阻滞剂。

Evaluation of the sesquiterpene (-)-alpha-bisabolol as a novel peripheral nervous blocker.

机构信息

Laboratório de Tecnologia Farmacêutica, Universidade Federal da Paraíba, João Pessoa, PB, Brazil.

出版信息

Neurosci Lett. 2010 Mar 12;472(1):11-5. doi: 10.1016/j.neulet.2010.01.042. Epub 2010 Jan 25.

Abstract

Essential oils are natural, complex and multi-component systems composed mainly of terpenes in addition to some other non-terpenes compounds that are widely used to prevent and treat human diseases. (-)-alpha-Bisabolol is an unsaturated monocyclic sesquiterpene alcohol found as the major constituent of many essential oils, like the German chamomile (Chamomilla recutita (L.) Rauschert), a plant reported to reduce the perception of acute pain and used for centuries for their medicinal properties. Recently, our group demonstrated the antinociceptive-like effect promoted by other terpenes could be associated with the decreased peripheral nerve excitability. Therefore, this study investigated the pharmacological activities of (-)-alpha-bisabolol on mice peripheral nervous system observing the changes on the compound action potential (CAP) characteristics. Using modified single sucrose-gap method in mice sciatic nerves, we acquired CAP recordings in the absence and presence of (-)-alpha-bisabolol (0.5, 1, 5 and 10mM). We observed that this sesquiterpene was able to reduce the neuronal excitability in a concentration-dependent manner, although, such effects were not reversed when the nerve was submitted to wash out. Assessing CAP parameters of depolarization and repolarization, we noticed similarities between (-)-alpha-bisabolol and lidocaine but not with 4-aminopyridine that are considered good blockers for sodium and potassium voltage-gated channels, respectively. Additionally, we also characterized the non-use-dependent profile of (-)-alpha-bisabolol action, in contrast to lidocaine. Thus, we suggested that decreased nervous excitability elicited by (-)-alpha-bisabolol might be caused by an irreversible blockade of voltage-dependent sodium channels.

摘要

精油是天然的、复杂的多组分系统,主要由萜烯组成,此外还有一些其他非萜烯化合物,被广泛用于预防和治疗人类疾病。(-)-α- 红没药醇是一种不饱和单环倍半萜醇,是许多精油的主要成分,如德国甘菊(Chamomilla recutita (L.) Rauschert),这种植物被报道能降低急性疼痛的感知,几个世纪以来一直因其药用特性而被使用。最近,我们的研究小组证明,其他萜烯类化合物的镇痛样作用可能与外周神经兴奋性的降低有关。因此,本研究通过观察复合动作电位(CAP)特性的变化,研究了(-)-α-红没药醇对小鼠周围神经系统的药理活性。我们使用改良的单蔗糖间隙法在小鼠坐骨神经上进行 CAP 记录,在(-)-α-红没药醇(0.5、1、5 和 10mM)存在和不存在的情况下进行 CAP 记录。我们观察到,这种倍半萜烯能够以浓度依赖的方式降低神经元兴奋性,尽管当神经被冲洗掉时,这种作用并没有逆转。评估去极化和复极化的 CAP 参数,我们注意到(-)-α-红没药醇与利多卡因之间的相似性,但与 4-氨基吡啶没有相似性,4-氨基吡啶分别被认为是钠和钾电压门控通道的良好阻断剂。此外,我们还对(-)-α-红没药醇的非使用依赖性作用进行了特征描述,与利多卡因相反。因此,我们认为(-)-α-红没药醇引起的神经兴奋性降低可能是由于电压依赖性钠通道的不可逆阻断。

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