Neuronal ion channel modulation by Drimys winteri compounds: Opening a new chemical space to neuropharmacology.

IF 5.9 2区 医学 Q2 CELL BIOLOGY
Neural Regeneration Research Pub Date : 2026-04-01 Epub Date: 2025-06-19 DOI:10.4103/NRR.NRR-D-24-01194
Macarena E Meza, Oscar Ramirez-Molina, Oscar Flores, Katherine Fariña-Oliva, Pamela A Godoy, Jorge Fuentealba, Gonzalo E Yévenes
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Abstract

Numerous pathological states of the nervous system involve alterations in neuronal excitability and synaptic dysfunction, which depend on the function of ion channels. Due to their critical involvement in health and disease, the search for new compounds that modulate these proteins is still relevant. Traditional medicine has long been a rich source of neuroactive compounds. For example, the indigenous Mapuche people have used the leaves and bark of the Drimys winteri tree for centuries to treat various diseases. Consequently, several studies have investigated the biological effects of compounds in Drimys winteri , highlighting sesquiterpenes such as α-humulene, drimenin, polygodial, and α-, β-, γ-eudesmol. However, there is currently no literature review focusing on the ability of these sesquiterpenes to modulate ion channels. This review summarizes the current knowledge about neuroactive compounds found in Drimys winteri , with special emphasis on their direct actions on neuronal ion channels. Several Drimys winteri sesquiterpenes modulate a diverse array of neuronal ion channels, including transient receptor potential channels, gamma-aminobutyric acid A receptors, nicotinic acetylcholine receptors, and voltage-dependent Ca 2+ and Na + channels. Interestingly, the modulation of these molecular targets by Drimys winteri sesquiterpenes correlates with their therapeutic actions. The promiscuous pharmacological profile of Drimys winteri sesquiterpenes suggests they modulate multiple protein targets in vivo , making them potentially useful for treating complex, multifactorial diseases. Further studies at the molecular level may aid in developing multi-targeted drugs with enhanced therapeutic effects.

冬青化合物对神经元离子通道的调节:为神经药理学开辟新的化学空间。
摘要:神经系统的许多病理状态涉及神经元兴奋性和突触功能障碍的改变,这取决于离子通道的功能。由于它们对健康和疾病的重要作用,寻找调节这些蛋白质的新化合物仍然是有意义的。传统医学长期以来一直是神经活性化合物的丰富来源。例如,几个世纪以来,土著马普切人一直使用冬青树的叶子和树皮来治疗各种疾病。因此,一些研究对冬虫夏草中化合物的生物学效应进行了研究,重点研究了倍半萜类化合物,如α-葎草烯、菟丝子苷、多聚醚和α-、β-、γ-菟丝子酚。然而,目前尚无文献综述关注这些倍半萜调节离子通道的能力。本文综述了冬青中神经活性化合物的研究进展,重点介绍了它们对神经元离子通道的直接作用。几种冬青倍半萜调节多种神经元离子通道,包括瞬时受体电位通道、γ -氨基丁酸a受体、烟碱乙酰胆碱受体和电压依赖性Ca2+和Na+通道。有趣的是,冬青倍半萜对这些分子靶点的调节与其治疗作用相关。冬虫夏草倍半萜的混杂药理学特征表明,它们在体内调节多种蛋白质靶点,使它们有可能用于治疗复杂的多因素疾病。在分子水平上的进一步研究可能有助于开发具有增强治疗效果的多靶点药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Neural Regeneration Research
Neural Regeneration Research CELL BIOLOGY-NEUROSCIENCES
CiteScore
8.00
自引率
9.80%
发文量
515
审稿时长
1.0 months
期刊介绍: Neural Regeneration Research (NRR) is the Open Access journal specializing in neural regeneration and indexed by SCI-E and PubMed. The journal is committed to publishing articles on basic pathobiology of injury, repair and protection to the nervous system, while considering preclinical and clinical trials targeted at improving traumatically injuried patients and patients with neurodegenerative diseases.
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