Peony glycosides reverse the effects of corticosterone on behavior and brain BDNF expression in rats

School of Chinese Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong.
Behavioural brain research (Impact Factor: 3.03). 11/2011; 227(1):305-9. DOI: 10.1016/j.bbr.2011.11.016
Source: PubMed


Repeated injections of corticosterone (CORT) induce the dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, resulting in depressive-like behavior. This study aimed to examine the antidepressant-like effect and the possible mechanisms of total glycosides of peony (TGP) in the CORT-induced depression model in rats. The results showed that the 3-week CORT injections induced the significant increase in serum CORT levels in rats. Repeated CORT injections also caused depression-like behavior in rats, as indicated by the significant decrease in sucrose consumption and increase in immobility time in the forced swim test. Moreover, it was found that brain-derived neurotrophic factor (BDNF) protein levels in the hippocampus and frontal cortex were significantly decreased in CORT-treated rats. Treatment of the rats with TGP significantly suppressed the depression-like behavior and increased brain BDNF levels in CORT-treated rats. The results suggest that TGP produces an antidepressant-like effect in CORT-treated rats, which is possibly mediated by increasing BDNF expression in the hippocampus and frontal cortex.

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    • "If reelin plays a role in the pathogenesis of depression, then chronic antidepressant treatment that reverses behavioral symptoms of depression and deficient neuronal maturation in chronically stressed rats should also resolve deficits in hippocampal reelin expression. In this experiment, we examined this hypothesis using a preclinical rat model in which 21 daily injections of the stress hormone CORT produce robust increases in depression-like behavior (Brummelte and Galea, 2010;Gregus et al., 2005;Hill et al., 2003;Kalynchuk et al., 2004;Mao et al., 2012;Marks et al., 2009;Ulloa et al., 2010;Wong et al., 2011;Workman et al., 2013). Our findings revealed that CORT increases depression-like behavior in the forced swim test, decreases the number of reelin + cells in the subgranular zone and hilus, and alters the number and complexity of immature neurons in the granule cell layer. "
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    ABSTRACT: We have hypothesized that a downregulation of reelin and deficient maturation of adult-born hippocampal neurons are important factors in the pathogenesis of depression. This hypothesis is based on previous work showing that depression-like behavior in rats treated with protracted corticosterone develops in concert with decreased dendritic complexity in newborn hippocampal granule neurons and decreased reelin expression in the proliferative subgranular zone of the dentate gyrus. In addition, heterozygous reeler mice with approximately 50% of normal brain levels of reelin are more vulnerable to the depressogenic effects of corticosterone than wildtype mice. The purpose of this experiment was to provide pharmacological validation for the link between reelin, neuronal maturation, and depression by examining whether the deleterious effects of corticosterone on these measures could be prevented by co-administration of the antidepressant imipramine. Rats received corticosterone injections, corticosterone injections plus either 10 or 15mg/kg imipramine injections, or vehicle injections for 21 consecutive days. They were then subjected to the forced swim test to assess depression-like behavior and sacrificed for immunohistochemical examination of immature neuron number and dendritic complexity and the presence of reelin+cells. We found that corticosterone increases depression-like behavior, decreases the number of reelin+cells in the subgranular zone, and decreases the number and complexity of immature neurons in the granule cell layer. All of these behavioral and cellular phenotypes were prevented by imipramine, providing further support for the idea that reelin is involved in the pathogenesis of depression. Copyright © 2015. Published by Elsevier Inc.
    Full-text · Article · Feb 2015 · Progress in Neuro-Psychopharmacology and Biological Psychiatry
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    • "Furthermore, peony root was demonstrated to have sedative [60] and antidepressant-like effects in mice [61-66]. The antidepressant-like effect of peony root could be, at least in part, mediated by inhibiting monoamine oxidase activity, hypothalamic-pituitary-adrenal axis activation, oxidative stress, and up-regulated brain-derived neurotrophic factor [62-66]. "
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    ABSTRACT: This article reviews the effectiveness of Kampo (traditional Japanese herbal medicine) in the treatment of functional gastrointestinal disorders, especially functional dyspepsia (FD) and irritable bowel syndrome (IBS). The results of four randomized, controlled trials (RCTs) suggested the usefulness of rikkunshito in relieving the subjective symptoms of patients with FD. Rikkunshito significantly improved not only gastric symptoms, such as epigastiric discomfort, but also extra-gastric symptoms, such as general fatigue, when compared with control drugs. The therapeutic effects of rikkunshito were more evident when it was prescribed to patients with “kyosho”, i.e., low energy. Two RCTs suggested the efficacy of keishikashakuyakuto for IBS. Basic research studies have demonstrated that these Kampo medicines have multiple sites of action to improve subjective symptoms. For example, rikkunshito improves gastric motility dysfunction, including impaired adaptive relaxation and delayed gastric emptying, gastric hypersensitivity, and anorexia via facilitation of ghrelin secretion. It also exhibits anti-stress effects, i.e., it attenuates stress-induced exacerbation of gastric sensation and anorexia, as well as the hypothalamic-pituitary-adrenocortical axis and sympathetic activation. Keishikashakuyakuto exhibited not only an antispasmodic effect on intestinal smooth muscle, but also antidepressant-like effects. Case series suggest that other Kampo prescriptions are also effective for FD and IBS. However, further studies are necessary to evaluate their efficacy.
    Full-text · Article · Jan 2014 · BioPsychoSocial Medicine
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    • "Sucrose preference test was carried out 24 h after the last injection . The test was performed as described previously (Mao et al., 2012b). Briefly, 72 h before the test, mice were trained to adapt 1% sucrose solution (w/v): two bottles of 1% sucrose solution were placed in each cage, and 24 h later 1% sucrose in one bottle was replaced with tap water for 24 h. "
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    ABSTRACT: A mouse model of depression has been recently developed by exogenous corticosterone administration. The present study aimed to examine the antidepressant-like effect and the possible mechanisms of piperine, a major alkaloid of black pepper (Piper nigrum Linn.) and long pepper (Piperlongum Linn.), in corticosterone-induced depression in mice. The results showed that 3-weeks corticosterone injections caused depression-like behavior in mice, as indicated by the significant decrease in sucrose consumption and increase in immobility time in the forced swim test and tail suspension test. Moreover, it was found that brain-derived neurotrophic factor protein and mRNA levels in the hippocampus were significantly decreased in corticosterone-treated mice. Treating the animals with piperine significantly suppressed behavioral and biochemical changes induced by corticosterone. The results suggest that piperine produces an antidepressant-like effect in corticosterone-treated mice, which is possibly mediated by increasing brain-derived neurotrophic factor expression in the hippocampus.
    Preview · Article · Jan 2014 · Neurochemistry International
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