Departamento de Farmacia, División de Ciencias Naturales y Exactas, Universidad de Guanajuato, Guanajuato, Guanajuato, Mexico.
Instituto de Neurobiología, Universidad Nacional Autónoma de México, Juriquilla, Querétaro, Mexico.
Drug Dev Res. 2020 Aug;81(5):600-608. doi: 10.1002/ddr.21659. Epub 2020 Mar 17.
This work describes the neuropharmacological (sedative, anxiolytic, antidepressant, and anticonvulsant) actions of Gardenin A (GA) (0.1-25 mg/kg p.o.), a flavonoid found in medicinal plants. The sedative effects of GA were assessed with the pentobarbital-induced sleep test. The anxiolytic actions of GA were evaluated with the elevated plus-maze, the light-dark box test, the exploratory cylinder assay, and the open field test. Motor coordination was evaluated with the rotarod test and the open field test. The antidepressant-like actions of GA were evaluated with the tail suspension test and forced swimming test. The mechanisms of the anxiolytic-like and antidepressant-like effects of GA were assessed using inhibitors of neurotransmission pathways. The anticonvulsant activity of GA was evaluated with the strychnine-induced seizure test. The sedative effects of GA were evident only at a dose of 25 mg/kg, which increased the duration of sleep but did not alter sleep onset. GA showed anxiolytic-like actions with activity comparable to that of clonazepam in all experimental tests. The GABA receptor antagonist bicuculline reversed the anxiolytic-like effects of GA. Furthermore, GA showed significant antidepressant-like actions in both models with activity comparable to that of fluoxetine. Yohimbine, an α2-adrenoceptor blocker, inhibited the antidepressant-like actions of GA. In addition, GA (1-10 mg/kg) did not affect locomotor coordination in mice and delayed the onset of convulsions. These findings suggest that GA induces anxiolytic-like effects and has anticonvulsant actions by the possible involvement of the GABAergic system. The antidepressant-like actions of GA may be mediated by noradrenergic neurotransmission.
本工作描述了在药用植物中发现的类黄酮 Gardenin A（GA）（0.1-25mg/kg，po）的神经药理学（镇静、抗焦虑、抗抑郁和抗惊厥）作用。GA 的镇静作用通过戊巴比妥钠诱导的睡眠试验进行评估。GA 的抗焦虑作用通过高架十字迷宫、明暗箱试验、探索性圆柱试验和旷场试验进行评估。运动协调通过转棒试验和旷场试验进行评估。GA 的抗抑郁样作用通过悬尾试验和强迫游泳试验进行评估。使用神经递质传递途径抑制剂评估 GA 的抗焦虑样和抗抑郁样作用的机制。GA 的抗惊厥活性通过士的宁诱发的惊厥试验进行评估。GA 的镇静作用仅在 25mg/kg 剂量时明显，增加睡眠时间但不改变睡眠起始。GA 在所有实验测试中均显示出与氯硝西泮相当的抗焦虑样作用。GABA 受体拮抗剂荷包牡丹碱逆转了 GA 的抗焦虑样作用。此外，GA 在两种模型中均表现出显著的抗抑郁样作用，其活性与氟西汀相当。α2-肾上腺素受体阻滞剂育亨宾抑制了 GA 的抗抑郁样作用。此外，GA（1-10mg/kg）在小鼠中不影响运动协调，并且延迟惊厥发作的发生。这些发现表明，GA 通过可能涉及 GABA 能系统诱导抗焦虑样作用，并具有抗惊厥作用。GA 的抗抑郁样作用可能由去甲肾上腺素能神经传递介导。
