Department of Basic Sciences, Faculty of Veterinary Medicine, Shahid Bahonar University of Kerman, Kerman, Iran.
Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.
Mol Biol Rep. 2022 Feb;49(2):1133-1139. doi: 10.1007/s11033-021-06939-0. Epub 2021 Nov 19.
Salicylic acid (SA) is a natural phenolic compound in plants with many beneficial effects for humans. The anxiolytic effect of this compound has been reported in animal models, but its mechanism of action remains unclear. In this study, by using the fear potentiated plus maze test, we evaluated the effect of salicylic acid on the gene expression of the main form of GABA (gamma aminobutyric acid) synthesizing enzyme i.e., the enzyme glutamic acid decarboxylase 67 (GAD67) which is called GAD1, in the ventral subiculum of the hippocampus, one of the main brain structures, in anxiety circuits. Also, the hypnotic effect of Salicylic acid was evaluated.
Animals were divided into the solvent, (SA) and diazepam treated groups (n = 6). For evaluating the anxiolytic effect of Salicylic acid, animals were subjected to 2 h of isolation, before placing them in the elevated plus maze (EPM). Afterward, the ventral part of the hippocampus was removed for evaluating the change in GAD1 gene expression by the reverse transcription-quantitative polymerase chain reaction (RTqPCR) technique. The hypnotic effect of Salicylic acid was evaluated in the ketamine induced sleeping test.
Salicylic acid at 10 and 30 (mg/kg) increased time spent and entries to the open arms in the (EPM) (p < 0.05). (RTqPCR) revealed that 30 mg/kg of Salicylic acid increased GAD1 gene expression (p < 0.001). Salicylic acid (30 and 300 mg/kg) also increased the duration of sleep, in ketamine induced sleeping test (p < 0.05).
Our results showed that Salicylic acid has anxiolytic and hypnotic effects and it exerts its anxiolytic effect partly, via up the regulation of GAD1 in the ventral part of the hippocampus.
水杨酸是植物中一种天然的酚类化合物，对人类有许多有益的影响。这种化合物的抗焦虑作用在动物模型中已有报道，但作用机制尚不清楚。在这项研究中，我们通过使用恐惧增强的旷场测试，评估了水杨酸对海马腹侧下托中主要 GABA（γ-氨基丁酸）合成酶即谷氨酸脱羧酶 67（GAD67）基因表达的影响，GAD67 也被称为 GAD1，它是焦虑回路中主要的脑结构之一。此外，还评估了水杨酸的催眠作用。
动物被分为溶剂组（SA）和地西泮处理组（n=6）。为了评估水杨酸的抗焦虑作用，动物在放入高架十字迷宫（EPM）之前先进行 2 小时的隔离。之后，取出海马腹侧部分，通过逆转录定量聚合酶链反应（RTqPCR）技术评估 GAD1 基因表达的变化。在氯胺酮诱导的睡眠试验中评估水杨酸的催眠作用。
水杨酸（10 和 30mg/kg）增加了 EPM 中的敞口臂停留时间和进入次数（p<0.05）。（RTqPCR）显示，30mg/kg 的水杨酸增加了 GAD1 基因表达（p<0.001）。水杨酸（30 和 300mg/kg）也增加了氯胺酮诱导的睡眠试验中的睡眠时间（p<0.05）。
我们的结果表明，水杨酸具有抗焦虑和催眠作用，它通过上调海马腹侧部分的 GAD1 来发挥部分抗焦虑作用。
