scholarly journals The Antidepressive and Anxiolytic Effects of Formula Consisted of Poria cocos and Cordyceps militaris Waster Medium Extract in Unpredictable Chronic Mild Stress Animal Model

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1212-1212
Author(s):  
Huai-Syuan Huang ◽  
Hsin-Yu Wu ◽  
Wan-Ting Chang ◽  
Yu-En Lin ◽  
Yun-Ju Huang ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
P38 Mapk ◽  
Chronic Mild Stress ◽  
Cordyceps Militaris ◽  
Sucrose Preference ◽  
Mild Stress ◽  
Depression And Anxiety ◽  
Fruiting Bodies ◽  
Poria Cocos ◽  
Unpredictable Chronic Mild Stress

Abstract Objectives According to the WHO report, depression will be the first of the global burden of diseases in 2030. There is more than fifty % of people suffered from depression and anxiety. However, only less than half of the patients receive appropriate treatments due to its side effects of the antidepressants and anxiolytics. Poria cocos (PC) and Cordyceps militaris (CM) are historically used as a complementary therapy to treat depression and anxiety because of its anti-inflammation ability. Instead of fruiting bodies, C. militaris waster medium (CMWM) is a by-product and containing a higher amount of cordycepin than fruiting bodies. Thus, this study aims to investigate the anti-depressive and anti-anxiety effects of extract formula (PC-CMWM) via the regulation of inflammation pathways. Methods Unpredictable chronic mild stress (UCMS) model was used in this study to induce depression-like and anxiety-like behaviors in rats. The 6 weeks-old male Sprague Dawley rats were divided into five groups: control (CTL), UCMS-vehicle (NCTL), and three PC-CMWM groups (low, medium, and high dosage). The sucrose preference test and elevated plus maze (EPM) were preformed after UCMS for 35 days. The neurotransmitters (serotonin and dopamine) were measured by HPLC. The pro-inflammatory cytokines IL-1β and glutamate in the amygdala and serum were analyzed, and the proteins of p38 MAPK and NF-κB related to inflammation were evaluated by western blotting. Results PC-CMWM reversed the behavioral deficiency induced by UCMS exposure, including body weight loss, food intake, and sucrose preference compared to NCTL group (P < 0.05). In the EPM analysis, rats supplemented with PC-CMWM significantly increased the time spent in open arm than those in NCTL (P < 0.05). Besides, treatment with PC-CMWM significantly reduced glutamate in the amygdala and metabolic of serotonin and dopamine in the prefrontal cortex (P < 0.05) compared with NCTL. PC-CMWM improved the IL-1β in serum and reduced p38 MAPK and NF-κB protein expression in the prefrontal cortex (P < 0.05) compared with that in NCTL rats. Conclusions PC-CMWM exhibited anti-depressive and anxiolytic effects via reducing inflammation and modulating neurotransmitters and it can be used as a functional food to prevent depression and anxiety. Funding Sources TARI1073027.

scholarly journals The selective 5-HT1A receptor biased agonists, F15599 and F13714, show antidepressant-like properties after a single administration in the mouse model of unpredictable chronic mild stress

2021 ◽  
Author(s):  
Monika Głuch-Lutwin ◽  
Kinga Sałaciak ◽  
Alicja Gawalska ◽  
Marek Jamrozik ◽  
Joanna Sniecikowska ◽  
...  
Keyword(s):  
Forced Swim Test ◽  
Dose Range ◽  
Chronic Mild Stress ◽  
Sucrose Preference ◽  
Long Term Memory ◽  
Mild Stress ◽  
Activity Levels ◽  
Single Administration ◽  
Unpredictable Chronic Mild Stress ◽  
Immobility Time

Abstract Rationale The prevalence of depression is ever-increasing throughout the population. However, available treatments are ineffective in around one-third of patients and there is a need for more effective and safer drugs. Objectives The antidepressant-like and procognitive effects of the “biased agonists” F15599 (also known as NLX-101) which preferentially targets postsynaptic 5-HT1A receptors and F13714, which targets 5-HT1A autoreceptors, were investigated in mice. Methods Antidepressant-like properties of the compounds and their effect on cognitive functions were assessed using the forced swim test (FST) and the novel object recognition (NOR), respectively. Next, we induced a depressive-like state by an unpredictable chronic mild stress (UCMS) procedure to test the compounds’ activity in the depression model, followed by measures of sucrose preference, FST, and locomotor activity. Levels of phosphorylated cyclic AMP response element-binding protein (p-CREB) and phosphorylated extracellular signal-regulated kinase (p-ERK1/2) were also determined. Results F15599 reduced immobility time in the FST over a wider dose-range (2 to 16 mg/kg po) than F13714 (2 and 4 mg/kg po), suggesting accentuated antidepressant-like properties in mice. F15599 did not disrupt long-term memory consolidation in the NOR at any dose tested, while F13714 impaired memory formation, notably at higher doses (4–16 mg/kg). In UCMS mice, a single administration of F15599 and F13714 was sufficient to robustly normalize depressive-like behavior in the FST but did not rescue disrupted sucrose preference. Both F15599 and F13714 rescued cortical and hippocampal deficits in p-ERK1/2 levels of UCMS mice but did not influence the p-CREB levels. Conclusions Our studies showed that 5-HT1A receptor biased agonists such as F13714 and especially F15599, due to its less pronounced side effects, might have potential as fast-acting antidepressants.

Strain differences in sucrose preference and in the consequences of unpredictable chronic mild stress

2004 ◽  
Vol 155 (1) ◽  
pp. 135-146 ◽  
Author(s):  
Stéphanie Pothion ◽  
Jean-Charles Bizot ◽  
Fabrice Trovero ◽  
Catherine Belzung
Keyword(s):  
Strain Differences ◽  
Chronic Mild Stress ◽  
Sucrose Preference ◽  
Mild Stress ◽  
Unpredictable Chronic Mild Stress

scholarly journals Analysis of Antidepressant-like Effects and Action Mechanisms of GSB-106, a Small Molecule, Affecting the TrkB Signaling

2021 ◽  
Vol 22 (24) ◽  
pp. 13381
Author(s):  
Yulia V. Vakhitova ◽  
Tatiana S. Kalinina ◽  
Liana F. Zainullina ◽  
Anastasiya Yu. Lusta ◽  
Anna V. Volkova ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Chronic Mild Stress ◽  
Tail Suspension Test ◽  
Brain Structures ◽  
Mild Stress ◽  
Stress Model ◽  
Pronounced Increase ◽  
Unpredictable Chronic Mild Stress ◽  
Porsolt Test ◽  
Action Mechanisms

Induction of BDNF-TrkB signaling is associated with the action mechanisms of conventional and fast-acting antidepressants. GSB-106, developed as a small dimeric dipeptide mimetic of BDNF, was previously shown to produce antidepressant-like effects in the mouse Porsolt test, tail suspension test, Nomura water wheel test, in the chronic social defeat stress model and in the inflammation-induced model of depression. In the present study, we evaluated the effect of chronic per os administration of GSB-106 to Balb/c mice under unpredictable chronic mild stress (UCMS). It was observed for the first time that long term GSB-106 treatment (1 mg/kg, 26 days) during ongoing UCMS procedure ameliorated the depressive-like behaviors in mice as indicated by the Porsolt test. In addition, chronic per os administration of GSB-106 resulted in an increase in BDNF levels, which were found to be decreased in the prefrontal cortex and hippocampus of mice after UCMS. Furthermore, prolonged GSB-106 treatment was accompanied by an increase in the content of pTrkB706/707 in the prefrontal cortex and by a pronounced increase in the level of pTrkB816 in both studied brain structures of mice subjected to UCMS procedure. In summary, the present data show that chronic GSB-106 treatment produces an antidepressant-like effect in the unpredictable chronic mild stress model, which is likely to be associated with the regulation of the BDNF-TrkB signaling.

scholarly journals Merging the Multi-Target Effects of Kleeb Bua Daeng, a Thai Traditional Herbal Formula in Unpredictable Chronic Mild Stress-Induced Depression

2021 ◽  
Vol 14 (7) ◽  
pp. 659
Author(s):  
Juthamart Maneenet ◽  
Orawan Monthakantirat ◽  
Supawadee Daodee ◽  
Chantana Boonyarat ◽  
Yutthana Chotritthirong ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Chronic Mild Stress ◽  
Antidepressant Activity ◽  
Piper Nigrum ◽  
Psychiatric Disease ◽  
Mild Stress ◽  
Herbal Formula ◽  
Necrosis Factor Alpha ◽  
Unpredictable Chronic Mild Stress

Major depressive disorder (MDD) is a common and debilitating psychiatric disease characterized by persistent low mood, lack of energy, hypoactivity, anhedonia, decreased libido, and impaired cognitive and social functions. However, the multifactorial etiology of MDD remains largely unknown due the complex interaction between genetics and environment involved. Kleeb Bua Daeng (KBD) is a Thai traditional herbal formula that has been used to promote brain health. It consists of a 1:1:1 ratio of the aerial part of Centella asiatica, Piper nigrum fruit, and the petals of Nelumbo nucifera. According to the pharmacological activities of the individual medicinal plants, KBD has good potential as a treatment for MDD. The present study investigated the antidepressant activity of KBD in an unpredictable chronic mild stress (UCMS) mouse model. Daily administration of KBD to UCMS mice ameliorated both anhedonia, by increasing 2% sucrose intake, and hopeless behavior, by reducing immobility times in the forced swimming test (FST) and tail suspension test (TST) without any effect on locomotor activity. The mechanism of KBD activity was multi-modal. KBD promoted neurogenesis by upregulation of brain-derived neurotrophic factor (BDNF) and cyclic AMP-responsive element binding (CREB) mRNA expression in the frontal cortex and hippocampus. Daily treatment with KBD significantly reversed UCMS-induced HPA axis dysregulation by upregulating the glucocorticoid receptor (GR) while downregulating serum- and glucocorticoid-inducible kinase 1 (SGK1) and FK506 binding protein 5 (FKBP5) mRNA expression. KBD treatment also normalized proinflammatory cytokine expression including tumor necrosis factor-alpha (TNF-α), and interleukin (IL)-1β and IL-6. KBD and its component extracts also exhibited an inhibitory effect in vitro on monoamine oxidase (MAO) A and B. The multiple antidepressant actions of KBD emphasize its potential as an effective, novel treatment for MDD.

scholarly journals Strain Differences in the Chronic Mild Stress Animal Model of Depression and Anxiety in Mice

2014 ◽  
Vol 22 (5) ◽  
pp. 453-459 ◽  
Author(s):  
Yang-Hee Jung ◽  
Sa-Ik Hong ◽  
Shi-Xun Ma ◽  
Ji-Young Hwang ◽  
Jun-Sup Kim ◽  
...  
Keyword(s):  
Animal Model ◽  
Strain Differences ◽  
Chronic Mild Stress ◽  
Mild Stress ◽  
Depression And Anxiety ◽  
Animal Model Of Depression
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