de Oliveira Denise Dias, da Silva Cassio Prinholato, Iglesias Bruno Benincasa, Beleboni Renê O
Department of Biotechnology, University of Ribeirão Preto, Ribeirão Preto, Brazil.
School of Medicine, University of Ribeirão Preto, Ribeirão Preto, Brazil.
Front Pharmacol. 2020 Aug 11;11:1181. doi: 10.3389/fphar.2020.01181. eCollection 2020.
Different types of epilepsy and forms of pathological anxiety have been described as significant neurological disorders that may exist as comorbidities. Some of those disorders share the association of affected limbic areas/neuropathological triggers as well as the use of drugs for their clinical management. The aim of this work was to investigate the anticonvulsant and anxiolytic properties of the vitexin (apigenin-8-C-glucoside), since this compound is a flavonoid usually found as one of the major constituents in several medicinal plants claimed as anxiolytics and/or anticonvulsants. This investigation was performed by the use of a series of classical murine animal models of chemically induced-seizures and of anxiety-related tests (open-field, elevated plus-maze, and light-dark box tests). Here, we show that the systemic administration of vitexin (1.25; 2.5 and 5 mg/kg; i.p.) exhibited selective protection against chemically-induced seizures. Vitexin did not block seizures evoked by glutamate receptors agonists (NMDA and kainic acid), and it did not interfere with the latencies for these seizures. Conversely, the same treatments protected the animals in a dose-dependent manner against the seizures evoked by the Gabaergic antagonists picrotoxin and PTZ and rise the latency time for the first seizure on non-protected animals. The higher dose of vitexin protected 100% of animals against the tonic-clonic seizures triggered by GABA antagonists. The results from open-field, elevated plus-maze, and light-dark box tests indicated the anxiolytic properties of vitexin at similar range of doses described for the anticonvulsant action screening. Furthermore, these results pointed that vitexin did not cause sedation or locomotor impairment on animals. The selective action of vitexin against picrotoxin and PTZ may reinforce the hypothesis by which this compound acts mainly by the modulation of GABAergic neurotransmission and/or related pathways. This could be useful to explain the dual activity of vitexin as anticonvulsant and anxiolytic, and highlight the pharmacological interest on this promising flavonoid.
不同类型的癫痫和病理性焦虑形式已被描述为可能以合并症形式存在的重大神经系统疾病。其中一些疾病存在受影响的边缘区域/神经病理学触发因素的关联，以及用于临床治疗的药物使用情况。这项工作的目的是研究牡荆素（芹菜素 - 8 - C - 葡萄糖苷）的抗惊厥和抗焦虑特性，因为这种化合物是一种黄酮类化合物，通常是几种声称具有抗焦虑和/或抗惊厥作用的药用植物的主要成分之一。这项研究通过使用一系列化学诱导癫痫的经典小鼠动物模型和与焦虑相关的测试（旷场试验、高架十字迷宫试验和明暗箱试验）来进行。在此，我们表明，全身性给予牡荆素（1.25；2.5和5毫克/千克；腹腔注射）对化学诱导的癫痫发作具有选择性保护作用。牡荆素不会阻断由谷氨酸受体激动剂（NMDA和 kainic 酸）诱发的癫痫发作，并且它不会干扰这些癫痫发作的潜伏期。相反，相同的处理以剂量依赖性方式保护动物免受GABA能拮抗剂印防己毒素和戊四氮诱发的癫痫发作，并延长未受保护动物首次癫痫发作的潜伏期。牡荆素的较高剂量可使100%的动物免受GABA拮抗剂引发的强直阵挛性癫痫发作。旷场试验、高架十字迷宫试验和明暗箱试验的结果表明，在用于抗惊厥作用筛选的相似剂量范围内，牡荆素具有抗焦虑特性。此外，这些结果表明牡荆素不会对动物造成镇静或运动功能障碍。牡荆素对印防己毒素和戊四氮的选择性作用可能强化了这样一种假设，即该化合物主要通过调节GABA能神经传递和/或相关途径发挥作用。这可能有助于解释牡荆素作为抗惊厥和抗焦虑药物的双重活性，并突出这种有前景的黄酮类化合物的药理学意义。
