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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

Representative Western blot analysis (a) and immunohistochemical staining (b) of CRHR1 and CRHR2 in the hippocampus. CRHR: corticotropin-releasing hormone receptor. Refer to Table 2 for the semiquantitative analysis of the above images.
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fig4: Representative Western blot analysis (a) and immunohistochemical staining (b) of CRHR1 and CRHR2 in the hippocampus. CRHR: corticotropin-releasing hormone receptor. Refer to Table 2 for the semiquantitative analysis of the above images.

Mentions: The expression of CRHR2 was upregulated in the model group unlike the control group. The expression was significantly downregulated by XYS and fluoxetine treatment. No significant difference was observed in the expression of CRHR1 among the four groups (Figure 4).


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)

Representative Western blot analysis (a) and immunohistochemical staining (b) of CRHR1 and CRHR2 in the hippocampus. CRHR: corticotropin-releasing hormone receptor. Refer to Table 2 for the semiquantitative analysis of the above images.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig4: Representative Western blot analysis (a) and immunohistochemical staining (b) of CRHR1 and CRHR2 in the hippocampus. CRHR: corticotropin-releasing hormone receptor. Refer to Table 2 for the semiquantitative analysis of the above images.
Mentions: The expression of CRHR2 was upregulated in the model group unlike the control group. The expression was significantly downregulated by XYS and fluoxetine treatment. No significant difference was observed in the expression of CRHR1 among the four groups (Figure 4).

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