Liquiritigenin reverses depression-like behavior in unpredictable chronic mild stress-induced mice by regulating PI3K/Akt/mTOR mediated BDNF/TrkB pathway

Tao, Weiwei; Dong, Yu; Su, Qiang; Wang, Hanqing; Chen, Yanyan; Xue, Wenhao; Chen, Chang; Xia, Baomei; Duan, Jin‐Ao; Chen, Gang

doi:10.1016/j.bbr.2016.04.039

Cited by 99 publications

(62 citation statements)

References 44 publications

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“…The same results were found after HJDT treatment in FST. The decrease of total traveled distance, central distance ratio, and central time in OFT indicate a lower desire to explore, which may mimic psychomotor retardation [24]. Additionally, the low levels of rearing in OFT, and the increased immobility time in FST are often used as indices of a despair state [25, 26].…”

Section: Discussionmentioning

confidence: 99%

“…Recently, Peng et al reported the iNOS inhibitor 1400 W exhibited a significant protection on neurons compared with CUS group [41]. TNF- α , IL-6, and IL-10 also played important roles in depression induced by stress, which caused the increase of proinflammation cytokines, including TNF- α , IL-6, and IL-1 β in serum and hippocampus [24, 42]. Our results have confirmed that HJDT decreased the microglia number and the proinflammation cytokines concentration.…”

Section: Discussionmentioning

confidence: 99%

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Huanglian‐Jie‐Du‐Tang Extract Ameliorates Depression‐Like Behaviors through BDNF‐TrkB‐CREB Pathway in Rats with Chronic Unpredictable Stress

Zhong

Liu

et al. 2017

Evidence-Based Complementary and Alternative Medicine

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Neuroinflammation is considered as one of the common pathogeneses of depression. Huanglian-Jie-Du-Tang (HJDT) is a traditional Chinese herbal formula. The present study investigates the antidepressant-like effect of HJDT and its possible mechanism in rats. Rats were given HJDT (2, 4, and 8 g/kg, intragastrically), paroxetine (1.8 mg/kg, intragastrically), or an equivalent volume of saline for 42 days. The depression-related behaviors, including sucrose preference test (SPT), open field test (OFT), novel objective recognition task (NORT), and forced swimming test (FST), were detected. 5-Hydroxytryptamine (5-HT) and dopamine (DA) contents, microglial activation, proinflammatory cytokines, and brain derived neurotrophic factor (BDNF), tropomyosin receptor kinases B (TrkB), and cAMP-responsive element binding protein (CREB) expression were investigated. The results indicated HJDT (2 and 4 g/kg) dramatically ameliorated the depression-like behaviors. Also HJDT decreased the number of microglia and the proinflammatory cytokines in hippocampus. Western-blotting analysis displayed HJDT upregulated BDNF, TrkB, and pCREB/CREB expression in hippocampus. Particularly, pCREB DNA activity enhanced with HJDT treatment in hippocampus. But there was no difference in the 5-HT and DA contents with HJDT treatment. In conclusion, it was supposed that HJDT might be a potential Chinese medicine decoction for treating or alleviating complex symptoms of depression through BDNF-TrkB-CREB pathway.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Huanglian‐Jie‐Du‐Tang Extract Ameliorates Depression‐Like Behaviors through BDNF‐TrkB‐CREB Pathway in Rats with Chronic Unpredictable Stress

Zhong

Liu

et al. 2017

Evidence-Based Complementary and Alternative Medicine

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“…It has been shown that activation of the phosphoinositide-3-kinase/serine-threonine kinase Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway could have very crucial effects on cell proliferation and apoptosis of cells involved in brain function (Tessier et al, 2015). Weiwei Tao et al showed that Liquiritigenin could alleviate depressive-like symptoms induced by CUMS, and this protective role might be conducted through regulating PI3K/Akt/mTOR mediated BDNF/TrkB pathway in CUMS mice hippocampus (Tao et al, 2016). Our previous study showed that cerebral ischemic injury may inactivate PI3K/Akt/mTOR pathways.…”

Section: Introductionmentioning

confidence: 99%

miR-16 and Fluoxetine Both Reverse Autophagic and Apoptotic Change in Chronic Unpredictable Mild Stress Model Rats

Yang

et al. 2017

Front. Neurosci.

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In the clinic selective serotonin reuptake inhibitors (SSRIs), like Fluoxetine, remain the primary treatment for major depression. It has been suggested that miR-16 regulates serotonin transporters (SERT) via raphe nuclei and hippocampal responses to antidepressants. However, the underlying mechanism and regulatory pathways are still obtuse. Here, a chronic unpredicted mild stress (CUMS) depression model in rats was established, and then raphe nuclei miR-16 and intragastric Fluoxetine injections were administered for a duration of 3 weeks. An open field test and sucrose preference quantification displayed a significant decrease in the CUMS groups when compare to the control groups, however these changes were attenuated by both miR-16 and Fluoxetine treatments. A dual-luciferase reporter assay system verified that hsa-miR-16 inhibitory effects involve the targeting of 3′UTR on the 5-HTT gene. Expression levels of miR-16 and BDNF in the hippocampus were examined with RT-PCR, and it was found that increased 5-HT2a receptor expression induced by CUMS can be decreased by miR-16 and Fluoxetine administration. Immunofluorescence showed that expression levels of neuron NeuN and MAP-2 in CUMS rats were lower. Apoptosis and autophagy levels were evaluated separately through relative expression of Bcl-2, Caspase-3, Beclin-1, and LC3II. Furthermore, CUMS was found to decrease levels of hippocampal mTOR, PI3K, and AKT. These findings indicate that apoptosis and autophagy related pathways could be involved in the effectiveness of antidepressants, in which miR-16 participates in the regulation of, and is likely to help integrate rapid therapeutic strategies to alleviate depression clinically. These findings indicate that miR-16 participates in the regulation of apoptosis and autophagy and could account for some part of the therapeutic effect of SSRIs. This discovery has the potential to further the understanding of SSRIs and accelerate the development of new treatments for depression.

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“…Several studies have implicated PI3K in synaptic plasticity, learning and memory, and major depression. Lipid products formed by PI3K activation act as second messengers by recruiting proteins, such as AKT, resulting in the activation of its downstream kinases, possibly by a mechanism dependent on the synthesis and release of BDNF, with the consequent increase in mTOR phosphorylation (Tao et al, ); mTOR is a target of the ERK and AKT pathways and activation of mTOR signaling stimulates mRNA translation and protein synthesis by activating of p70S6K, causing rapid and sustained elevation of synapse‐associated proteins, including PSD95, which is responsible for several functions, including scaffold and organization of receptors, such as α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptors (Lu et al, ). PSD95, the main protein of excitatory postsynaptic density material composition, plays an important role in synaptic plasticity.…”

Section: Discussionmentioning

confidence: 99%

Schisandrae Chinensis Fructus inhibits behavioral deficits induced by sleep deprivation and chronic unpredictable mild stress via increased signaling of brain‐derived neurotrophic factor

Yan

Sun

Xiao

et al. 2019

Phytotherapy Research

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The present study was undertaken to explore the interactions between sleep deprivation (SD) and Schisandrae Chinensis Fructus (SCF) treatment in the antidepressant‐like effects. We observed that SD aggravated the anxiety‐like behavior induced by chronic unpredictable mild stress (CUMS) in the elevated plus maze test. However, the forced swimming test and sucrose preference test showed that SD (12 hr) alleviated the depressive symptoms and SD (72 hr) has the opposite effects. Administration of SCF showed a promising therapeutic effect on depression and anxiety induced by CUMS and SD. Moreover, SCF could potential strengthen the antidepressant‐like effects of SD (12 hr) according to the behavioral tests. In addition, the BDNF level in hippocampus was elevated by SD (12 hr) and SCF treatment and together with the upregulation of TrkB/CREB/ERK and PI3K/AKT/GSK3β/mTOR signaling pathways. Besides, the protein levels of p70S6K and PSD95, which are downstream targets of mTOR, also increased by the treatment. These results indicated that the antidepressant‐like effect of SCF in the CUMS depends on the activation of BDNF and the modulation of TrkB/CREB/ERK and PI3K/AKT/GSK3β/mTOR signaling cascades, and SD (12 hr) shared a common etiology consisting of complex bidirectional interactions with SCF.

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Liquiritigenin reverses depression-like behavior in unpredictable chronic mild stress-induced mice by regulating PI3K/Akt/mTOR mediated BDNF/TrkB pathway

Cited by 99 publications

References 44 publications

Huanglian‐Jie‐Du‐Tang Extract Ameliorates Depression‐Like Behaviors through BDNF‐TrkB‐CREB Pathway in Rats with Chronic Unpredictable Stress

Huanglian‐Jie‐Du‐Tang Extract Ameliorates Depression‐Like Behaviors through BDNF‐TrkB‐CREB Pathway in Rats with Chronic Unpredictable Stress

miR-16 and Fluoxetine Both Reverse Autophagic and Apoptotic Change in Chronic Unpredictable Mild Stress Model Rats

Schisandrae Chinensis Fructus inhibits behavioral deficits induced by sleep deprivation and chronic unpredictable mild stress via increased signaling of brain‐derived neurotrophic factor

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