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薰衣草和迷迭香提取物对T型钙通道的调节作用。

Modulation of T-type Ca2+ channels by Lavender and Rosemary extracts.

作者信息

El Alaoui Chaymae, Chemin Jean, Fechtali Taoufiq, Lory Philippe

机构信息

Institut de Génomique Fonctionnelle, CNRS, INSERM, University of Montpellier, Montpellier, France.

LabEx 'Ion Channel Science and Therapeutics', Montpellier, France.

出版信息

PLoS One. 2017 Oct 26;12(10):e0186864. doi: 10.1371/journal.pone.0186864. eCollection 2017.

Abstract

Medicinal plants represent a significant reservoir of unexplored substances for early-stage drug discovery. Of interest, two flowering Mediterranean plants have been used for thousands of years for their beneficial effects on nervous disorders, including anxiety and mood. However, the therapeutic potential of these plants regarding their ability to target ion channels and neuronal excitability remains largely unknown. Towards this goal, we have investigated the ability of Lavender and Rosemary to modulate T-type calcium channels (TTCCs). TTCCs play important roles in neuronal excitability, neuroprotection, sensory processes and sleep. These channels are also involved in epilepsy and pain. Using the whole-cell patch-clamp technique, we have characterized how Lavender and Rosemary extracts, as well as their major active compounds Linalool and Rosmarinic acid, modulate the electrophysiological properties of recombinant TTCCs (CaV3.2) expressed in HEK-293T cells. Both the methanolic and essential oil extracts as well as the active compounds of these plants inhibit Cav3.2 current in a concentration-dependent manner. In addition, these products also induce a negative shift of the steady-state inactivation of CaV3.2 current with no change in the activation properties. Taken together, our findings reveal that TTCCs are a molecular target of the Lavender and Rosemary compounds, suggesting that inhibition of TTCCs could contribute to the anxiolytic and the neuroprotective effects of these plants.

摘要

药用植物是早期药物发现中未被探索物质的重要宝库。有趣的是,两种地中海开花植物数千年来一直因其对包括焦虑和情绪在内的神经紊乱具有有益作用而被使用。然而,这些植物在靶向离子通道和神经元兴奋性方面的治疗潜力在很大程度上仍不为人知。为了实现这一目标,我们研究了薰衣草和迷迭香调节T型钙通道(TTCCs)的能力。TTCCs在神经元兴奋性、神经保护、感觉过程和睡眠中发挥重要作用。这些通道也与癫痫和疼痛有关。使用全细胞膜片钳技术,我们已经表征了薰衣草和迷迭香提取物以及它们的主要活性化合物芳樟醇和迷迭香酸如何调节在HEK-293T细胞中表达的重组TTCCs(CaV3.2)的电生理特性。这些植物的甲醇提取物、精油提取物以及活性化合物均以浓度依赖性方式抑制Cav3.2电流。此外,这些产物还会使CaV3.2电流的稳态失活产生负向偏移,而激活特性没有变化。综上所述,我们的研究结果表明TTCCs是薰衣草和迷迭香化合物的分子靶点,这表明抑制TTCCs可能有助于这些植物的抗焦虑和神经保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1a9/5658086/ef33b923a6be/pone.0186864.g001.jpg

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