Abstract：
Natural products can act as potential GABA modulators, avoiding the undesirable effects of traditional pharmacology used for the inhibition of the central nervous system such as benzodiazepines (BZD). Phenolics, especially flavonoids and phlorotannins, have been considered as modulators of the BZD-site of GABAA receptors (GABAARs), with sedative, anxiolytic or anticonvulsant effects. However, the wide chemical structural variability of flavonoids shows their potential action at more than one additional binding site on GABAARs, which may act either negatively, positively, by neutralizing GABAARs, or directly as allosteric agonists. Therefore, the aim of the present review is to compile and discuss an update of the role of phenolics, namely as pharmacological targets involving dysfunctions of the GABA system, analyzing both their different compounds and their mechanism as GABAergic modulators. We focus this review on articles written in English since the year 2010 until the present. Of course, although more research would be necessary to fully establish the type specificity of phenolics and their pharmacological activity, the evidence supports their potential as GABAAR modulators, thereby favoring their inclusion in the development of new therapeutic targets based on natural products. Specifically, the data compiled in this review allows for the directing of future research towards ortho-dihydroxy diterpene galdosol, the flavonoids isoliquiritigenin (chalcone), rhusflavone and agathisflavone (biflavonoids), as well as the phlorotannins, dieckol and triphlorethol A. Clinically, flavonoids are the most interesting phenolics due to their potential as anticonvulsant and anxiolytic drugs, and phlorotannins are also of interest as sedative agents.
摘要：
天然产物可以作为潜在的GABA调节剂，避免用于抑制中枢神经系统的传统药理学的不良影响，例如苯二氮卓类药物（BZD）。酚类物质,尤其是黄酮类化合物和邻苯三酮,已被认为是GABAA受体（GABAAR）的BZD位点的调节剂，用镇静剂,抗焦虑或抗惊厥作用。然而,黄酮类化合物广泛的化学结构变异性显示了它们在GABAAR上一个以上的额外结合位点的潜在作用，这可能会产生负面影响，积极，通过中和GABAAR，或直接作为变构激动剂。因此,本审查的目的是汇编和讨论酚类物质作用的最新情况，即作为涉及GABA系统功能障碍的药理学靶标，分析它们的不同化合物及其作为GABA能调节剂的机制。我们将此评论重点放在自2010年至今的英语文章上。当然,尽管需要更多的研究来充分确定酚类物质的类型特异性及其药理活性，证据支持它们作为GABAAR调节剂的潜力，从而有利于将它们纳入基于天然产物的新治疗靶标的开发中。具体来说,这篇综述中汇编的数据可以指导未来对邻二羟基二萜galdosol的研究，类黄酮异甘草素（查尔酮），rhusflavoneandagathisflavone(bifetoids),以及苯三酚,Dieckol和三苯三醇A.临床，黄酮类化合物是最有趣的酚类物质，因为它们具有抗惊厥和抗焦虑药物的潜力，和间氯单宁也作为镇静剂感兴趣。
