Xiaoyaosan exerts antidepressant-like effects by regulating the functions of astrocytes and EAATs in the prefrontal cortex of mice

Liu, Yan; Ding, Xin; Wang, Xinxing; Zou, Xiaojuan; Li, Xiaojuan; Liu, Yue-yun; Li, Jie; Qian, Xiu-yun; Chen, Jiaxu

doi:10.1186/s12906-019-2613-6

Cited by 27 publications

(22 citation statements)

References 51 publications

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“…It has been demonstrated that Xiaoyaosan can decrease the Hamilton Depression Rating Scale (HAMD) and Self-Rating Depression Scale (SDS) scores in depression patients (Feng et al, 2014;Feng et al, 2016). Xiaoyaosan has been demonstrated to ameliorate chronic unpredictable mild stress (CUMS)-induced depression-like behaviors (Liu et al, 2019) and promote neuronal plasticity in HT22 cells. Xiaoyaosan can protect against corticosterone-induced stress injury in primary hippocampal neurons (PHNs) (Cao et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Xiaoyaosan Alleviates Hippocampal Glutamate-Induced Toxicity in the CUMS Rats via NR2B and PI3K/Akt Signaling Pathway

Zhou

Liu

et al. 2021

Front. Pharmacol.

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Purpose: It is revealed that Xiaoyaosan could reduce glutamate level in the hippocampus of depressed rats, whose metabolism leads to the pathophysiology of depression. However, the underlying mechanism remains unclear. This study aims to explore the effect of Xiaoyaosan on glutamate metabolism, and how to regulate the excitatory injury caused by glutamate.Methods: Rats were induced by chronic unpredictable mild stress, then divided into control, vehicle (distilled water), Xiaoyaosan, fluoxetine, vehicle (DMSO), Xiaoyaosan + Ly294002 and Ly294002 groups. Ly294002 was microinjected into the lateral ventricular catheterization at 5 mM. Xiaoyaosan (2.224 g/kg) and fluoxetine (2.0 mg/kg) were orally administered for three weeks. The open field test (OFT), forced swimming test (FST), and sucrose preference test (SPT) were used to assess depressive behavior. The glutamate and corticosterone (CORT) levels were detected by ELISA. Western blot, immunochemistry or immunofluorescence were used to detect the expressions of NR2B, MAP2, PI3K and P-AKT/Akt in the hippocampal CA1 region. The mRNA level of MAP2, NR2B and PI3K were detected by RT-qPCR.Results: Compared to the rats in control group, body weight and food intake of CUMS rats was decreased. CUMS rats also showed depression-like behavior as well as down regulate the NR2B and PI3K/Akt signaling pathway. Xiaoyaosan treatments could increase food intake and body weight as well as improved time spent in the central area, total distance traveled in the OFT. Xiaoyaosan could also decrease the immobility time as well as increase the sucrose preference in SPT. Moreover, xiaoyaosan decreased the level of glutamate in the hippocampal CA1 region and serum CORT in CUMS rats. Furthermore, xiaoyaosan improved the expression of MAP2 as well as increased the expression of NR2B, PI3K and the P-AKT/AKT ratio in the hippocampal CA1 region in the CUMS rats.Conclusion: Xiaoyaosan treatment can exert the antidepressant effect by rescuing hippocampal neurons loss induced by the glutamate-mediated excitotoxicity in CUMS rats. The underlying pathway maybe through NR2B and PI3K/Akt signaling pathways. These results may suggest the potential of Xiaoyaosan in preventing the development of depression.

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Section: Introductionmentioning

confidence: 99%

Xiaoyaosan Alleviates Hippocampal Glutamate-Induced Toxicity in the CUMS Rats via NR2B and PI3K/Akt Signaling Pathway

Zhou

Liu

et al. 2021

Front. Pharmacol.

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“…CUMS procedure followed during treatment. The dosage of Flu and Bup obtained from previous studies (Yi et al, 2013) and the volume of concentration and volume of the gavage administration of Psycodigest determined based on human and mouse dose conversion formula (Liu et al 2019).…”

Section: Drugs and Administrationmentioning

confidence: 99%

“…and the volume of concentration and volume of the gavage administration of Psycodigest determined based on human and mouse dose conversion formula(Liu et al 2019). Behavioral testThe sucrose preference test (SPT)At the end of treatment, the Sucrose preference test was performed as described previously(Mao et al, 2009).…”

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confidence: 99%

WITHDRAWN: The Chronic Administration of Persian Herbal Formulas Psycodigest Induced The Antidepressant-Like Effect in a Chronic Unpredictable Mild Stress (CUMS) Mouse Model

Gavzan

Araghi

Abbasabadi

et al. 2021

Preprint

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Depression is one of the most common mental disorders. Despite the numerous medications, there are still the limitations such as side effects and treatment-resistance in depression treating. Herbal medicine has been considered as supplemental and alternative therapy for psychiatric disorders. Psycodigest is an antidepressant Persian formula composed of Aloysia triphylla, Citrus aurantium, Echium amoneum, Lavandula angustifolia, Melissa officinalis, Salix aegyptiaca, Valeriana officinalis, Viola odorata, and Cinnamomum zeylanicum. This survey was performed to evaluate the effect of the chronic administration of Psycodigest in chronic unpredictable mild stress (CUMS) mice behavior and its safety. CUMS-mice orally administered with Psycodigest (0.23ml /mice), Fluoxetine (20mg/kg), and Bupropion (15mg/kg) for 4 weeks. The antidepressant effects were evaluated by sucrose preference, tail suspension, and forced swimming test. The anxiolytic effect was tested by elevated plus maze. Besides, the brain, kidney, liver super oxidase dismutase (SOD) activity, and plasma level of cortisol, creatinine and alanine aminotransferase (ALT) were detected. The histopathological effects evaluated on kidney, liver, intestine and brain. The daily oral administration of Psycodigest as well as Fluoxetine and Bupropion had antidepressant, but no anxiolytic effect. Psycodigest did not change the serum level of cortisol, ALT and creatinine. Also hematological and histological examinations were not affected. Meanwhile, the brain SOD activity increased followed by Psycodigest treatment, the kidney and liver SOD did not change. The chronic administration of Psycodigest significantly ameliorated the depressive-like behaviors and showed the antioxidative effect in the brain with no toxicity in the liver and kidney.

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“…The Xiaoyaosan dry powder and the fluoxetine capsules were dissolved in distilled water, then the mice in the two treatment groups received Xiaoyaosan (0.254 g/kg/d) and fluoxetine (2.6 mg/kg/d) by intragastric administration after the daily CUMS procedure, respectively. 30 Meanwhile, mice in the control and CUMS group received 0.5 mL physiological saline.…”

Section: Methodsmentioning

confidence: 99%

Traditional Chinese Formula Xiaoyaosan Alleviates Depressive-Like Behavior in CUMS Mice by Regulating PEBP1-GPX4-Mediated Ferroptosis in the Hippocampus

Hu¹,

Yang²,

Yan³

et al. 2021

NDT

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Background At present, the pathogenesis of depression is not fully understood, and nearly half of depression patients experience no obvious effects during treatment. This study aimed to establish a depression mouse model to explore the possible role of ferroptosis in the pathogenesis of depression, and observe the effects of Xiaoyaosan on PEBP1-GPX4-mediated ferroptosis in the hippocampus. Methods Forty-eight male C57BL/6 mice were randomly divided into a control group, CUMS group, Xiaoyaosan group and fluoxetine group, and the model was established by chronic unpredictable mild stress (CUMS) for a successive 6 weeks. The medication procedure was performed from the 4th to the 6th week of modeling. The behavioral evaluations were measured to evaluate depressive-like behaviors. The expressions of GPX4, FTH1, ACSL4 and COX2 were detected as ferroptosis-related indicators. Then, the total iron and ferrous content in the hippocampus were measured. The levels of PEBP1 and ERK1/2 were observed, and the expressions of GFAP and IBA1 were also detected to measure the functions of astrocytes and microglia in the hippocampus. Results Eight herbs of Xiaoyaosan had 133 active ingredients which could regulate the 43 ferroptosis-related genes in depression. After 6 weeks of modeling, the data showed that mice in the CUMS group had obvious depressive-like behaviors, and medication with Xiaoyaosan or fluoxetine could significantly improve the behavioral changes. The expressions of GPX4, FTH1, ACSL4, COX2, PEBP1, ERK1/2, GFAP and IBA1 changed in the CUMS group mice, while the total iron and ferrous content also changed. Xiaoyaosan and fluoxetine had obvious curative effects that could significantly alleviate the above changes in the hippocampus. Conclusion Our results revealed that the activation of ferroptosis might exist in the hippocampi of CUMS-induced mice. The PEBP1-GPX4-mediated ferroptosis could be involved in the antidepressant mechanism of Xiaoyaosan. It also implied that ferroptosis could become a new target for research into the depression mechanism and antidepressant drugs.

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Xiaoyaosan exerts antidepressant-like effects by regulating the functions of astrocytes and EAATs in the prefrontal cortex of mice

Cited by 27 publications

References 51 publications

Xiaoyaosan Alleviates Hippocampal Glutamate-Induced Toxicity in the CUMS Rats via NR2B and PI3K/Akt Signaling Pathway

Xiaoyaosan Alleviates Hippocampal Glutamate-Induced Toxicity in the CUMS Rats via NR2B and PI3K/Akt Signaling Pathway

WITHDRAWN: The Chronic Administration of Persian Herbal Formulas Psycodigest Induced The Antidepressant-Like Effect in a Chronic Unpredictable Mild Stress (CUMS) Mouse Model

Traditional Chinese Formula Xiaoyaosan Alleviates Depressive-Like Behavior in CUMS Mice by Regulating PEBP1-GPX4-Mediated Ferroptosis in the Hippocampus

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