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Preclinical evidence of rapid-onset antidepressant-like effect in Radix Polygalae extract

Shin, Im-Joon ; Son, Sung Un ; Park, Hyunwoo ; Kim, Yoorim ; Park, Sung Hyun ; Swanberg, Kelley LU orcid ; Shin, Joo-Yeon ; Ha, Sang-Kyu ; Cho, Yoonju and Bang, Soo-Yong , et al. (2014) In PLoS ONE 9(2). p.1-10
Abstract

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... (More)

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.

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Contribution to journal
publication status
published
keywords
Animals, Antidepressive Agents/pharmacology, Behavior, Animal/drug effects, Chronic Disease, Depression/drug therapy, Disease Models, Animal, Dose-Response Relationship, Drug, Drugs, Chinese Herbal/pharmacology, Female, Glutamates/metabolism, Hippocampus/drug effects, Male, Mice, Mice, Inbred C57BL, Mice, Inbred ICR, Phosphorylation/drug effects, Phytotherapy, Plant Extracts/pharmacology, Protein Subunits/metabolism, Receptors, AMPA/metabolism, Stress, Psychological/drug therapy, Synapses/drug effects, TOR Serine-Threonine Kinases/metabolism, Time Factors
in
PLoS ONE
volume
9
issue
2
article number
e88617
pages
1 - 10
publisher
Public Library of Science (PLoS)
external identifiers
  • scopus:84895744868
  • pmid:24520403
ISSN
1932-6203
DOI
10.1371/journal.pone.0088617
language
English
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no
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8b102eae-70ad-4ade-b442-6b00b84d2115
date added to LUP
2023-09-18 15:04:03
date last changed
2024-01-04 04:43:24
@article{8b102eae-70ad-4ade-b442-6b00b84d2115,
  abstract     = {{<p>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.</p>}},
  author       = {{Shin, Im-Joon and Son, Sung Un and Park, Hyunwoo and Kim, Yoorim and Park, Sung Hyun and Swanberg, Kelley and Shin, Joo-Yeon and Ha, Sang-Kyu and Cho, Yoonju and Bang, Soo-Yong and Lew, Jae-Hwan and Cho, Seung-Hun and Maeng, Sungho}},
  issn         = {{1932-6203}},
  keywords     = {{Animals; Antidepressive Agents/pharmacology; Behavior, Animal/drug effects; Chronic Disease; Depression/drug therapy; Disease Models, Animal; Dose-Response Relationship, Drug; Drugs, Chinese Herbal/pharmacology; Female; Glutamates/metabolism; Hippocampus/drug effects; Male; Mice; Mice, Inbred C57BL; Mice, Inbred ICR; Phosphorylation/drug effects; Phytotherapy; Plant Extracts/pharmacology; Protein Subunits/metabolism; Receptors, AMPA/metabolism; Stress, Psychological/drug therapy; Synapses/drug effects; TOR Serine-Threonine Kinases/metabolism; Time Factors}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{1--10}},
  publisher    = {{Public Library of Science (PLoS)}},
  series       = {{PLoS ONE}},
  title        = {{Preclinical evidence of rapid-onset antidepressant-like effect in Radix Polygalae extract}},
  url          = {{http://dx.doi.org/10.1371/journal.pone.0088617}},
  doi          = {{10.1371/journal.pone.0088617}},
  volume       = {{9}},
  year         = {{2014}},
}