Shin Im-Joon, Son Sung Un, Park Hyunwoo, Kim Yoorim, Park Sung Hyun, Swanberg Kelley, Shin Joo-Yeon, Ha Sang-Kyu, Cho Yoonju, Bang Soo-Yong, Lew Jae-Hwan, Cho Seung-Hun, Maeng Sungho
Department of Applied Korean Medicine, College of Oriental Medicine, Kyung Hee University, Seoul, Korea.
Department of East-West Medicine, Graduate School of East-West Medical Science, Kyung Hee University, Yongin, Korea.
PLoS One. 2014 Feb 10;9(2):e88617. doi: 10.1371/journal.pone.0088617. eCollection 2014.
Radix Polygalae (the root of Polygala tenuifolia) is a herb widely used in traditional Asian medicine that is thought to exert a variety of neuropsychiatric effects. Radix Polygalae extract can protect against N-methyl D-aspartate (NMDA) neurotoxicity and induce brain-derived neurotrophic factor (BDNF) expression, suggesting modulatory roles at glutamatergic synapses and possible antidepressant action. In accordance with this hypothesis, Radix Polygalae extract demonstrated antidepressant-like effects in 8-week-old male C57Bl/6 mice by decreasing behavioral despair in the forced swim and tail suspension tasks and increasing hedonic-like behavior in the female urine sniffing test 30 minutes after a single oral administration of 0.1 mg/kg. Reduced latency to acquire a food pellet in the novely suppressed feeding paradigm, without change in anxiety-like behaviors suggested a rapid-onset nature of the antidepressant-like effect. In addition, it decreased the number of failed escapes in the learned helplessness paradigm after two oral administrations 24 hours and 30 minutes before the first test. Finally, it reversed anhedonia as measured by saccharin preference in mice exposed to the chronic stress model after two administrations of 0.1 mg/kg, in contrast to the repeated administration generally needed for similar effect by monoamergic antidepressants. Immobility reduction in tail suspension task was blocked by the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist NBQX, a pattern previously demonstrated by ketamine and other ketamine-like rapid-onset antidepressants. Also similarly to ketamine, Radix Polygalae appeared to acutely decrease phosphorylation of GluR1 serine-845 in the hippocampus while leaving the phosphorylation of hippocampal mTOR serine 2448 unchanged. These findings serve as preclinical evidence that Radix Polygalae extract exerts rapid-onset antidepressant effects by modulating glutamatergic synapses in critical brain circuits of depression and may be worthy of further evaluation as a safe substitute to other rapid-onset antidepressants known to have unacceptable side effects.
远志（远志的根）是一种在传统亚洲医学中广泛使用的草药，被认为具有多种神经精神作用。远志提取物可以保护免受N-甲基-D-天冬氨酸（NMDA）神经毒性，并诱导脑源性神经营养因子（BDNF）表达，提示其在谷氨酸能突触处具有调节作用以及可能的抗抑郁作用。根据这一假设，单次口服0.1mg/kg远志提取物30分钟后，8周龄雄性C57Bl/6小鼠在强迫游泳和悬尾试验中行为绝望减少，在雌性尿液嗅探试验中享乐样行为增加，显示出抗抑郁样作用。在新奇抑制摄食范式中获取食物颗粒的潜伏期缩短，而焦虑样行为无变化，提示抗抑郁样作用具有快速起效的特点。此外，在首次试验前24小时和30分钟进行两次口服给药后，它减少了习得性无助范式中失败逃脱的次数。最后，在给予0.1mg/kg两次后，与单胺能抗抑郁药通常需要重复给药才能产生类似效果不同，它逆转了慢性应激模型小鼠中通过糖精偏好测量的快感缺失。尾悬试验中不动时间的减少被α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体拮抗剂NBQX阻断，氯胺酮和其他类似氯胺酮的快速起效抗抑郁药也曾出现过这种模式。同样与氯胺酮相似，远志似乎能急性降低海马中GluR1丝氨酸-845的磷酸化，而海马mTOR丝氨酸2448的磷酸化保持不变。这些发现作为临床前证据表明，远志提取物通过调节抑郁症关键脑回路中的谷氨酸能突触发挥快速起效的抗抑郁作用，作为已知有不可接受副作用的其他快速起效抗抑郁药的安全替代品，可能值得进一步评估。
