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Xiao Yao San Improves Depressive-Like Behavior in Rats through Modulation of β-Arrestin 2-Mediated Pathways in Hippocampus.

Zhu X, Xia O, Han W, Shao M, Jing L, Fan Q, Liu Y, Diao J, Lv Z, Sun X - Evid Based Complement Alternat Med (2014)

Bottom Line: XYS was effective in ameliorating the depressive-like behavior and downregulating UCN2 and CORT.XYS decreased the expression of serine/threonine-protein phosphatase 2A subunit B and increased the expression of β-arrestin 2.In conclusion, XYS improves social isolation and CUMS-induced depressive-like behavior and ameliorates HPA hyperactivation through the downregulation of corticotrophin releasing hormone (CRH) receptor 2.

View Article: PubMed Central - PubMed

Affiliation: Department of Traditional Chinese Medicine, Nanfang Hospital, Southern Medical University, No. 1838, Guangzhou 510515, China ; The Key Laboratory of Molecular Biology, State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong 510515, China.

ABSTRACT
Xiao Yao San (XYS) is a classical Chinese medicine formula that has been widely used to treat mood disorders for hundreds of years. To confirm the effect of XYS and better understand its underlying mechanism, high-performance liquid chromatography-mass spectrometry analysis-based quality control of XYS extracts and proteomics-based identification of differential proteins in the hippocampus were adopted in social isolation and chronic unpredictable mild stress- (CUMS-) treated rats. The depressive-like behavior of rats induced by CUMS resembled the manifestation of human depression. The upregulated corticosterone (CORT) and urocortin 2 (UCN2) levels demonstrated the existence of hypothalamic-pituitary-adrenal (HPA) axis hyperactivity. XYS was effective in ameliorating the depressive-like behavior and downregulating UCN2 and CORT. XYS decreased the expression of serine/threonine-protein phosphatase 2A subunit B and increased the expression of β-arrestin 2. The expressions of brain-derived neurotrophic factor (BDNF), tyrosine receptor kinase B (TrkB), and mammalian target of rapamycin (mTOR) were also elevated by XYS. In conclusion, XYS improves social isolation and CUMS-induced depressive-like behavior and ameliorates HPA hyperactivation through the downregulation of corticotrophin releasing hormone (CRH) receptor 2. The upregulation of BDNF/TrkB and the phosphorylation of mTOR require β-arrestin 2 as a scaffold to regulate stress signaling.

No MeSH data available.


Related in: MedlinePlus

Effects of XYS on serum and cerebrospinal fluid hormone levels in depressive rats. Effect of XYS on serum ACTH (a), serum CORT (b), serum CRH (c), CSF CRH (d), serum urocortin 2 (e), and CSF urocortin (f). Data are expressed as mean ± SD, n = 6 per group. ACTH: adrenocorticotropic hormone; CORT: corticosterone; CRH: corticotropin-releasing hormone; CSF: cerebrospinal fluid. △P < 0.05, ▲P < 0.01 versus control, *P < 0.05, #P < 0.01 versus model.
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fig2: Effects of XYS on serum and cerebrospinal fluid hormone levels in depressive rats. Effect of XYS on serum ACTH (a), serum CORT (b), serum CRH (c), CSF CRH (d), serum urocortin 2 (e), and CSF urocortin (f). Data are expressed as mean ± SD, n = 6 per group. ACTH: adrenocorticotropic hormone; CORT: corticosterone; CRH: corticotropin-releasing hormone; CSF: cerebrospinal fluid. △P < 0.05, ▲P < 0.01 versus control, *P < 0.05, #P < 0.01 versus model.

Mentions: The serum CORT significantly increased in the model group unlike the control group (P < 0.05); serum and CSF UCN2 also increased (P < 0.01). XYS and fluoxetine significantly decreased the CORT level (P < 0.05) as well as the serum and CSF UCN2 levels (P < 0.01). No significant difference was observed in the serum and CSF levels of CRH and serum ACTH based on the ANOVA (Figure 2).


Xiao Yao San Improves Depressive-Like Behavior in Rats through Modulation of β-Arrestin 2-Mediated Pathways in Hippocampus.

Zhu X, Xia O, Han W, Shao M, Jing L, Fan Q, Liu Y, Diao J, Lv Z, Sun X - Evid Based Complement Alternat Med (2014)

Effects of XYS on serum and cerebrospinal fluid hormone levels in depressive rats. Effect of XYS on serum ACTH (a), serum CORT (b), serum CRH (c), CSF CRH (d), serum urocortin 2 (e), and CSF urocortin (f). Data are expressed as mean ± SD, n = 6 per group. ACTH: adrenocorticotropic hormone; CORT: corticosterone; CRH: corticotropin-releasing hormone; CSF: cerebrospinal fluid. △P < 0.05, ▲P < 0.01 versus control, *P < 0.05, #P < 0.01 versus model.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4109698&req=5

fig2: Effects of XYS on serum and cerebrospinal fluid hormone levels in depressive rats. Effect of XYS on serum ACTH (a), serum CORT (b), serum CRH (c), CSF CRH (d), serum urocortin 2 (e), and CSF urocortin (f). Data are expressed as mean ± SD, n = 6 per group. ACTH: adrenocorticotropic hormone; CORT: corticosterone; CRH: corticotropin-releasing hormone; CSF: cerebrospinal fluid. △P < 0.05, ▲P < 0.01 versus control, *P < 0.05, #P < 0.01 versus model.
Mentions: The serum CORT significantly increased in the model group unlike the control group (P < 0.05); serum and CSF UCN2 also increased (P < 0.01). XYS and fluoxetine significantly decreased the CORT level (P < 0.05) as well as the serum and CSF UCN2 levels (P < 0.01). No significant difference was observed in the serum and CSF levels of CRH and serum ACTH based on the ANOVA (Figure 2).

Bottom Line: XYS was effective in ameliorating the depressive-like behavior and downregulating UCN2 and CORT.XYS decreased the expression of serine/threonine-protein phosphatase 2A subunit B and increased the expression of β-arrestin 2.In conclusion, XYS improves social isolation and CUMS-induced depressive-like behavior and ameliorates HPA hyperactivation through the downregulation of corticotrophin releasing hormone (CRH) receptor 2.

View Article: PubMed Central - PubMed

Affiliation: Department of Traditional Chinese Medicine, Nanfang Hospital, Southern Medical University, No. 1838, Guangzhou 510515, China ; The Key Laboratory of Molecular Biology, State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong 510515, China.

ABSTRACT
Xiao Yao San (XYS) is a classical Chinese medicine formula that has been widely used to treat mood disorders for hundreds of years. To confirm the effect of XYS and better understand its underlying mechanism, high-performance liquid chromatography-mass spectrometry analysis-based quality control of XYS extracts and proteomics-based identification of differential proteins in the hippocampus were adopted in social isolation and chronic unpredictable mild stress- (CUMS-) treated rats. The depressive-like behavior of rats induced by CUMS resembled the manifestation of human depression. The upregulated corticosterone (CORT) and urocortin 2 (UCN2) levels demonstrated the existence of hypothalamic-pituitary-adrenal (HPA) axis hyperactivity. XYS was effective in ameliorating the depressive-like behavior and downregulating UCN2 and CORT. XYS decreased the expression of serine/threonine-protein phosphatase 2A subunit B and increased the expression of β-arrestin 2. The expressions of brain-derived neurotrophic factor (BDNF), tyrosine receptor kinase B (TrkB), and mammalian target of rapamycin (mTOR) were also elevated by XYS. In conclusion, XYS improves social isolation and CUMS-induced depressive-like behavior and ameliorates HPA hyperactivation through the downregulation of corticotrophin releasing hormone (CRH) receptor 2. The upregulation of BDNF/TrkB and the phosphorylation of mTOR require β-arrestin 2 as a scaffold to regulate stress signaling.

No MeSH data available.


Related in: MedlinePlus